Comparing the effects of serum GPER-1 and oxidant/antioxidant levels on retinopathy in patients with diabetes and healthy individuals: a pilot study / Comparando o impacto do soro GPER-1 e dos níveis de oxidante/antioxidante na retinopatia em pacientes diabéticos e em indivíduos saudáveis: um estudo piloto

ABSTRACT Purpose: This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. Methods: The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Results: Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Conclusions: Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.

RESUMO Objetivo: Esta pesquisa buscou determinar o im­pacto dos níveis de proteína G sérica no desenvolvimento da retinopatia em pacientes diabéticos, comparando-os a indivíduos saudáveis. Métodos: Foram incluídos, no estudo, 40 pacientes com retinopatia diabética (Grupo 1), 40 pacientes sem retinopatia diabética (Grupo 2) e 40 indivíduos saudáveis (Grupo 3). Os níveis hormonais de progesterona sérica, de proteína G sérica, estradiol, oxidante/antioxidante e hormônio liberado pela tireoide foram analisados e comparados. A análise post hoc foi realizada para comparar os subgrupos nos quais diferenças estatisticamente significativas foram encontradas. Resultados: Uma diferença significativa foi encontrada entre todos os grupos em termos de proteína G sérica, oxidante/antioxidante e níveis de estradiol (p<0.01), mas nenhuma diferença significativa foi encontrada em termos de hormônio liberado pela tireoide ou progesterona (p=0,496, p=0,220, respectivamente). Na análise post hoc dos grupos com diferenças estatisticamente significativas, outra diferença significativa foi encontrada entre todos os grupos para proteína G sérica e níveis oxidantes/antioxidantes (p<0,05). Os níveis de proteína G sérica e os níveis de oxidante foram positivamente correlacionados, enquanto os níveis de proteína G sérica e os níveis de antioxidantes foram negativamente correlacio­nados (r=0,622/p<0,01, r=0,453/p<0,01, r=0,460/p<0,01, respectivamente). A análise de regressão múltipla mos­trou que o aumento da proteína G sérica pode ajudar a prevenir a retinopatia diabética. Conclusões: Os níveis de proteína G sérica que eram mais altos no grupo de retinopatia diabética, aumentaram à medida que o equilíbrio oxidante/antioxidante mudou em favor do estresse oxidativo. Este parece ser um mecanismo de defesa para prevenir danos neuronais.

Immunofluorescence Analysis of Estrogen and Progesterone Receptors and Ki-67 Nuclear Protein in Canine Uteri Treated with Medroxyprogesterone Acetate During Anestrus / Análisis de Inmunofluorescencia de Receptores de Estrógeno y Progesterona y Proteína Nuclear Ki-67 en Úteros Caninos Tratados con Acetato de Medroxiprogesterona Durante el Anestr

SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.

Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

Papel de las hormonas progesterona, estradiol y oxitocina en la función del miometrio durante el embarazo y el trabajo de parto / Role of progesterone, estradiol and oxytocin hormones in myometrial function during pregnancy and labor

Resumen El trabajo de parto es la transición de un estado de inactividad y relajación muscular a un estado de excitación, en el cual la capa muscular del útero (miometrio) realiza crecientes contracciones coordinadas para llevar a cabo la expulsión del feto y la placenta. Durante el inicio del trabajo de parto, el miometrio experimenta una serie de cambios fisiológicos, bioquímicos y moleculares, pasando de un estado de quiescencia a un fenotipo contráctil que inducirá el parto. En parte, esto es provocado por la acción de las hormonas progesterona, estradiol y oxitocina. En general, la progesterona mantiene la quiescencia del miometrio durante el embarazo al inhibir la expresión de moléculas proinflamatorias y proteínas asociadas a la contracción, mientras que al término del embarazo, el estradiol induce la expresión de dichas moléculas. Por su parte, la oxitocina induce un aumento en la concentración de calcio intracelular para llevar a cabo las contracciones de los miocitos uterinos. El objetivo del presente trabajo es presentar un resumen acerca de los mecanismos moleculares involucrados en la regulación de la actividad de las células miometriales por medio de las hormonas progesterona, estradiol y oxitocina, así como discutir las perspectivas de esta interesante área de investigación.

Abstract Labor is the transition from a state of inactivity and muscle relaxation to a state of muscle excitation, in which the muscular layer of the uterus (myometrium) performs increasingly coordinated contractions to deliver the fetus and expel the placenta. During the onset of labor, the myometrium undergoes a series of physiological, biochemical, and molecular changes, allowing the tissue to transition from a quiescent state to a contractile phenotype that will support labor. This is partly caused by the action of the hormones progesterone, estradiol, and oxytocin. In general, progesterone maintains the quiescence of the myometrium during pregnancy by decreasing the expression of proinflammatory molecules and contraction-associated proteins. In contrast, at the end of pregnancy, estradiol induces the expression of these molecules. For its part, oxytocin induces an increase in intracellular calcium concentration to carry out the contractions of uterine myocytes. The objective of this review is to present a summary of the molecular mechanisms involved in regulating myometrial cell activity through the hormones progesterone, estradiol and oxytocin, as well as to discuss the perspectives of this exciting area of research.

Ovarian hormones influence immune response to liver ischemia-reperfusion

Liver injury occurs after ischemia and reperfusion (IR), as seen in transplant settings. Sex hormones have been implicated in many pathophysiological mechanisms in females and this could lead to liver protection under inflammatory reperfusion conditions where an excessive immune response occurs. Despite such assumptions, this fact needs to be further investigated. To address this, female and male C57BL/6J mice (8-12 weeks old) were studied. Bilateral ovariectomy (OVX) was performed in females to decrease estradiol levels. IR was performed, and after two weeks, all animals underwent a sham control operation or IR with euthanasia at the following time points after reperfusion: 6, 12, 24, and 48 h. IR triggered an inflammatory process in the liver with recruitment of neutrophils into the parenchyma of male mice. The female sham mice were protected against liver IR presenting no alteration of aminotransferase (ALT) levels compared to males. OVX caused loss of protection, increasing hepatic injury as represented by increased ALT levels and myeloperoxidase (MPO) activity. Female sham mice showed increased Akt phosphorylation and activation, while males showed reduced Akt activation. Estradiol pretreatment recovered ALT levels after IR injury, which was associated with decreased liver injury.

Fecal microbiota profile of ovariohysterectomized cats submitted to estrogen replacement / Perfil da microbiota fecal de gatas ovariohisterectomizadas submetidas à reposição estrogênica

This study aimed to observe the effects of 17 ß-estradiol replacements on the fecal microbiota in spayed cats. Individual samples of fresh feces were collected and stored at -80° C. Sequencing of the V3/V4 regions of the 16S rRNA gene was used, and bioinformatic analysis was performed. Firmicutes/Bacteriodetes ratio was lower in the group receiving estrogen replacement compared to the SHAM group (P = 0,005). Jaccard index (P = 0.123) and Yue & Clayton index (P = 0.094) did not reveal alpha and beta diversity differences. The linear discriminant analysis effect size (LefSe) identified Firmicutes and MegasPhaera as the biomarkers for the SHAM group, and Burkholderiales, Betaproteobacteria, Sutterellaceae, Suterella, Proteobacteria, Proteobacteria unclassified and Collinsella for the group receiving estrogen replacement.(AU)

O objetivo deste estudo foi observar os efeitos da reposição de 17 ß-estradiol na microbiota fecal de gatas castradas. Amostras individuais de fezes frescas foram colhidas e armazenadas a -80°C. Foi realizado o sequenciamento das regiões V3/V4 do gene 16S rRNA e a análise bioinformática. A razão Firmicutes/Bacteriodetes foi menor no grupo que recebeu reposição estrogênica em comparação ao grupo SHAM (P = 0,005). O índice de Jaccard (P = 0,123) e o índice de Yue & Clayton (P = 0,094) não revelaram diferenças na alfa e beta diversidade. A análise discriminatória linear de tamanho do efeito (LefSe) identificou Firmicutes e Megasphaera como biomarcadores para o grupo SHAM, e Burkholderiales, Betaproteobacteria, Sutterellaceae, Suterella, Proteobacteria, Proteobacteria não classificada e Collinsella para o grupo que recebeu reposição estrogênica.(AU)

Effects of Qingruxiao granules combined with tamoxifen on mammary hyperplasia and its effects on serum hypoxia inducible factor-1α, angiopoietin-2 and prolactin levels / 中国基层医药

Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.

Safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids / 中国基层医药

Objective:To analyze the safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids.Methods:The clinical data of 60 patients with uterine fibroids who were admitted to Zhejiang Veteran Hospital from February 2020 to February 2022 were retrospectively analyzed. These patients were divided into a control group and an observation group ( n = 30/group) according to different surgical methods. The control group underwent conventional surgery. The observation group underwent superselective embolization of the uterine arteries. Uterine size, uterine fibroid size, postoperative hormone level, and complications were compared between the two groups. Results:There was no significant difference in total response rate between the observation and control groups [93.33 (28/30) vs. 83.33 (25/30), χ2 = 1.46, P > 0.05]. After surgery, serum estradiol, luteinizing hormone, follicle-stimulating hormone, and progesterone levels in the observation group were (164.14 ± 19.97) ng/L, (2.43 ± 1.47) IU/L, (2.51 ± 1.14) IU/L, and (5.05 ± 0.43) μg/L, respectively, which were significantly lower than (190.23 ± 21.62) ng/L, (3.78 ± 1.63) IU/L, (3.94 ± 1.23) IU/L, (8.22 ± 1.35) μg/L in the control group ( t = 4.86, 3.37, 4.67, 12.25, all P < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group [3.33% (1/30) vs. 20.00% (6/30), χ2 = 4.04, P < 0.05). Conclusion:Compared with conventional surgery, superselective embolization of the uterine arteries is more effective on uterine fibroids, better keep postoperative hormone level stable, and reduce or avoid short- and long-term complications. Therefore, superselective embolization of the uterine arteries for the treatment of uterine fibroids deserves the clinical promotion.

Bloodletting at auricular dorsal vein combined with auricular point sticking for menstrual migraine of qi stagnation and blood stasis and its effect on serum levels of E2 and 5-HT / 中国针灸

OBJECTIVE@#To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism.@*METHODS@#A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment.@*RESULTS@#Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05).@*CONCLUSION@#Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.

Comparison of 17β-estradiol against retinal light damage in BALB/c or C57BL/6 mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the neuroprotective effect of 17β-estradiol(E2)on retina light damage in BALB/c and C57BL/6 mice and provide experimental data for the successful construction of a research model for E2 against retinal light damage.METHODS:Totally 40～45 adult female BALB/c or C57BL/6 mice were divided into six groups, 6 for each group: normal control, ovariectomized control, ovariectomized light(mice were stimulated with continuous white light at 10000 lx for 4, 8, 12, 16, and 24h after 14d of ovariectomy), intravitreal administration sham operation, saline and E2 pre-treatment groups(2μL saline or 10-5mol/L E2 were intravitreal injected respectively after 14d of ovariectomy operation and 24h of dark adaptation). The morphological and functional changes of the retina were detected by paraffin section HE staining, TUNEL staining and electroretinogram.RESULTS:In the ovariectomized light group, the thickness of the inner/outer nuclear layer decreased significantly from the 4h stimulation of 10000 lx white light group. Intravitreal administration of E2 significantly inhibited the apoptosis of retinal cells in the two strains of mice(P&#x003C;0.01)and the decrease of amplitudes of a- and b-waves in max-ERG of C57BL/6 mice(P&#x003C;0.05).CONCLUSION:The light loss sensitivity of two strains of mice was different under the same light stimulation. E2 had a protective effect on both morphology and function of the retina in BALB/c mice, and had a significant protective effect on retina function in C57BL/6 mice.

Associations of sex hormone levels with body mass index (BMI) in men: a cross-sectional study using quantile regression analysis / 亚洲男科学杂志(英文版)

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

Serum estradiol levels decrease after oophorectomy in transmasculine individuals on testosterone therapy / 亚洲男科学杂志(英文版)

Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.

Differences in COVID-19 mortality in males and females: Is estrogen hormone attributing to sex differences?

Objectives: Globally, the case fatality ratio is more in males versus females. Some studies have suggested estrogen hormone decreases susceptibility to SARS CoV-2. We have analyzed the observed sex differences in COVID-19 behavior in males and females and the clinical profiles of females of different age groups of COVID-19 patients and discussed their symptoms, laboratory evaluations, and associated comorbidities. Material and Methods: The patients were tested for COVID-19 through real-time RT-PCR (Reverse Transcription Polymerase Chain Reaction) assay. The data obtained were studied for the epidemiological, clinical, and laboratory characteristics from their medical records. Results: The mortality rate in females was 12.33% (36/292) whereas mortality in males was 19.63% (84/428). In between group analysis, 8.7% (14/161) of females died in the <40 years age group versus 16.8% (22/131) in more than 40 years age group whereas in males, the mortality was 13.7% (21/153) in <40 years versus 22.9%(63/275). The mortality rate in women older than 40 years was greater than mortality in younger females emphasizing the protection provided by estrogen hormone in them. The proportion of patients who expired due to COVID-19 significantly differs by age cutoff of 40 years, X2 (1, n = 428). The difference is statistically significant at P < 0.05. Males more than 40 years are more likely to expire. Conclusion: Sex-related differences in coronavirus pandemic have been found pointing toward the protective role of estrogen hormone and other differences in immunological behavior in males and females. Downregulation of ACE2 expression, thereby reducing viral entry, might also be contributory to decreasing mortality in females.

Annona muricata Linn Stem Bark Protects against Uterine Proliferative Disorder Induced by Estradiol Benzoate in Female Rat

Aim: The opening of mitochondrial permeability transition (mPT) pore is an important event in the execution of mitochondrial-mediated apoptosis. Some bioactive compounds elicit their chemotherapeutic effects against tumor/cancer cells via the induction of mitochondrial-mediated apoptosis. Annona muricata, a medicinal plant, is folklorically used in the treatment of tumors and cancers. This study therefore aimed at investigating the effect of methanol stem bark extract of Annona muricata (MEAM) on apoptosis via mPT pore and estradiol benzoate (EB)-induced proliferative disorder using female Wistar rats. Methodology: Mitochondria were isolated using differential centrifugation. The mPT pore opening, cytochrome c release and mitochondrial ATPase activity were determined spectrophotometrically. The levels of estrogen (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH), were determined using ELISA technique. Histological and histochemical assessments of the uterine sections were carried out using standard methods. Phytochemical constituents of MEAM were determined using Gas Chromatography-Mass Spectroscopy (GC-MS). Results: The in vitro results showed a significant induction of mPT pore opening, release of cytochrome c and enhancement of mitochondrial ATPase (mATPase) activity in a concentration-dependent manner. However, oral administration of MEAM did not induce rat uterine mPT pore opening, neither any significant release of cytochrome c nor enhancement of mATPase activity at the dosages used. Interestingly, MEAM reversed the EB-induced increase in E2, LH and FSH. The MEAM also improved the antioxidant milleu by reducing MDA level and increasing the SOD and GSH-Px activities in the treatment groups. Administration of EB induced endometrial hyperplasia in the model group which was mitigated by MEAM in the treatment group. The GC-MS analysis of MEAM revealed the presence of some important phytochemicals that are pharmacological relevant in cancer treatment. Conclusions: This study suggests that the methanol stem bark extract of Annona muricata contains bioactive compounds that protect against EB-induced uterine proliferative disorder in female Wistar rats.

Role of VPAC1 and VPAC2 receptors in the etiology of pregnancy rhinitis: an experimental study in rats / O papel dos receptores VPAC1 e VPAC2 na etiologia da rinite gestacional: um estudo experimental em ratos

Abstract Introduction: Pregnancy rhinitis is a common sex hormone-related otorhinolaryngological disorder. There are some epidemiological and physiological studies on pregnancy rhinitis, but histopathological and biomolecular changes have not been studied thoroughly. Objectives: The receptors VPAC1 and VPAC2 are known for their roles in allergic rhinitis. On the other hand, activation of subclinical allergy has been suggested in the pathophysiology of pregnancy rhinitis. Therefore, we aimed to compare the physiological and gestational pattern of VPAC1 and VPAC2 expression in rat nasal mucosa. Methods: Twenty adult Wister albino female rats were enrolled into the study. Two groups constituted as 10 control (group A) and 10 pregnant (group B) rats. They were fed ad libitum and sheltered at room temperature (22°±2°C). The rats were sacrificed at the 20th day of gestation by intraperitoneal injection of 400mg/kg Na-pentobarbitone. Then, 10 - 15 mL of blood was taken, and samples were reserved for the detection of serum estradiol and progesterone levels by ELISA test. The nasal septum was resected and divided in half for immunohistochemical analyses and real time polymerase chain reaction testing of VPAC1 and VPAC2. Results: VPAC1 and VPAC2 were found to be in all layers of septal specimens, but the immunostaining of surface epithelium was more distinct in specimens of both groups. We demonstrated higher overall staining intensity in the pregnant group. PCR revealed significant increase in expression of VPAC1 (p = 0.023) and VPAC2 (p = 0.021) in pregnant group when compared with control group. In addition, we demonstrated upregulatory effect of estradiol and progesterone on the vasoactive intestinal peptide receptor expression. Conclusions: Gestational up-regulation of nasal VPAC1 and VPAC2 was shown both by PCR and immunohistochemical analysis. These findings support the hypothesis that PR is caused by the activation of subclinical allergy that is present before pregnancy.

Resumo Introdução: A rinite gestacional é um distúrbio comum da otorrinolaringologia relacionado a hormônios sexuais. Existem alguns estudos epidemiológicos e fisiológicos sobre rinite gestacional, mas as alterações histopatológicas e biomoleculares ainda não foram estudadas completamente. Objetivo: Os receptores VPAC1 e VPAC2 são conhecidos por seu papel na rinite alérgica. Por outro lado, a ativação da alergia subclínica tem sido sugerida na fisiopatologia da rinite gestacional. Portanto, objetivamos comparar o padrão fisiológico e gestacional da expressão de VPAC1 e VPAC2 na mucosa nasal de ratos. Método: Vinte ratas fêmeas Wistar albinas adultas foram incluídas no estudo. Os dois grupos foram divididos em 10 ratas; controle (grupo A) e 10 ratas prenhes (grupo B). Elas foram alimentadas ad libitum e abrigadas em temperatura ambiente (22° ±2° C). Sacrificamos as ratas no 20° dia de gestação por injeção intraperitoneal de 400 mg/kg de sódio-pentobarbital. Em seguida, foram coletados 10 a 15 mL de sangue e as amostras foram reservadas para a detecção dos níveis séricos de estradiol e progesterona pelo método Elisa. O septo nasal foi ressecado e dividido em 2 para análises imuno-histoquímicas e testes de reação em cadeia da polimerase em tempo real, RT-PCR, de VPAC1 e VPAC2. Resultados: VPAC1 e VPAC2 foram encontrados em todas as camadas da amostra septal, mas a imunocoloração do epitélio de superfície foi mais distinta nas amostras de ambos os grupos. Demonstramos maior intensidade geral de coloração no grupo gestante. A reação de polimerase em cadeia revelou aumento significante na expressão de VPAC1 (p = 0,023) e VPAC2 (p = 0,021) no grupo gestante quando comparado ao grupo controle. Além disso, demonstramos um efeito up-regulador do estradiol e progesterona na expressão do receptor peptídeo intestinal vasoativo. Conclusão: A up-regulação gestacional dos receptores VPAC1 e VPAC2 nasais foi demonstrada tanto por reação de polimerase em cadeia quanto por análise imuno-histoquímica. Esses achados corroboram a hipótese de que a rinite gestacional é causada pela ativação de alergia subclínica presente antes da gestação.

Diseño y caracterización de un sistema de entrega de fármacos autoemulsificable (SEDDS) de estradiol por diagramas de fases pseudoternarios y pruebas fisicoquímicas

Introducción: el estradiol es una hormona esteroide sexual femenina usada ampliamente como terapia hormonal que presenta una baja biodisponibilidad, debido a su baja solubilidad acuosa y a su alta hidrofobicidad, perteneciendo a la clase II del sistema de clasificación de biofarmacéutica. Objetivos: diseñar y caracterizar un sistema de entrega de fármacos autoemulsificable (SEDDS) para el fármaco estradiol por pruebas fisicoquímicas con el fin de obtener la relación óptima que permitiera mejorar su solubilidad acuosa, velocidad de disolución y potencialmente su biodisponibilidad. Método: estudios de solubilidad en diferentes solventes, diagramas de fases pseudoternarios constituidos por aceites, tensioactivos, cotensioactivos y agua permitieron reconocer las diferentes regiones de formación de SEDDS e identificar los porcentajes de excipientes que conducen a la formación de soluciones isotrópicas; las formulaciones resultantes fueron caracterizadas en tiempo de autoemulsificación, robustez a la dilución, punto de nube y perfil de disolución en capsula dura. Resultados: las formulaciones que contenían Capmul MCM®, Kolliphor® RH40 y Transcutol®, tuvieron un tiempo de autoemulsificación de aproximadamente 1 min; fueron estables en tres distintos pH (1,2; 4,5 y 7,2), en diferentes volúmenes de dilución, exhibiendo una apariencia transparente, ligeramente azulada, sin precipitados, o separación de fases, puntos de nube mayores en comparación de las formulaciones que contenían Gelucire® 44/14. Conclusiones: las estrategias de caracterización empleadas en el desarrollo de esta investigación demostraron ser eficientes para la selección adecuada de excipientes y su proporción óptima para el diseño eficaz de un sistema de entrega de fármaco autoemulsificable (SEDDS).

SUMMARY Introduction: Estradiol is a female sex steroid hormone widely used as hormonal therapy that has low bioavailability, due to its low aqueous solubility and high hydro-phobicity, belonging to class II of the Biopharmaceutical Classification System. Aim: To design and characterize a self-emulsifying drug delivery system (SEDDS) for the drug estradiol by physicochemical tests to obtain the most optimal ratio that would improve its aqueous solubility, dissolution rate, and potentially its bioavailability. Method: Solubility studies in different solvents; pseudo ternary phase diagrams made up of oils, surfactants, co-surfactants, and water, allowed to recognize the different regions of SEDDS formation and identify the percentages of excipients that lead to the formation of isotropic solutions; The resulting formulations were characterized in autoemulsification time, robustness to dilution, cloud point and dissolution profile in a hard capsule. Results: The formulations containing Capmul MCM®, Kolliphor® RH40, and Transcutol®, had an autoemulsification time of approximately 1 minute; were stable at three different pHs (1.2, 4.5 and 7.2), at different dilution volumes, exhibiting a transparent, slightly bluish appearance, without precipitates, or phase separation, higher cloud points compared to the formulations containing Gelucire® 44/14. Conclusions: The characterization strategies used in the development of this research proved to be efficient for the adequate selection of excipients and their optimal ratio for the effective design of a self-emulsifying drug delivery system (SEDDS).

Introdução: o estradiol é um hormônio esteroide sexual feminino amplamente utilizado como terapia hormonal que apresenta baixa biodisponibilidade devido à sua baixa solubilidade aquosa e alta hidrofobicidade, pertencente à classe II do sistema de classificação biofarmacêutica. Objetivos: projetar e caracterizar um sistema de liberação de drogas autoemulsificante (SEDDS) para o fármaco estradiol por meio de testes físico-químicos a fim de obter a proporção ideal que melhore sua solubilidade aquosa, taxa de dissolução e potencialmente sua biodisponibilidade. Método: estudos de solubilidade em diferentes solventes, diagramas de fases pseudoternários compostos por óleos, tensoativos, cotensoativos e água permitiram reconhecer as diferentes regiões de formação de SEDDS e identificar as porcentagens de excipientes que levam à formação de soluções isotrópicas; as formulações resultantes foram caracterizadas quanto ao tempo de autoemulsificação, robustez à diluição, ponto de turvação e perfil de dissolução da cápsula dura. Resultados: as formulações contendo Capmul MCM®, Kolliphor® RH40 e Transcutol®, tiveram um tempo de autoemulsificação de aproximadamente 1 min; foram estáveis em três diferentes pH's (1,2; 4,5 e 7,2), em diferentes volumes de diluição, apresentando aspecto transparente, levemente azulado, sem precipitados ou separação de fases, pontos de turvação mais elevados em relação às formulações contendo Gelucire® 44/14. Conclusões: as estratégias de caracterização utilizadas no desenvolvimento desta pesquisa mostraram-se eficientes para a seleção adequada de excipientes e sua proporção ideal para o desenho eficaz de um sistema de liberação de fármacos autoemulsificante (SEDDS).

Cross-sectional analysis of gonadal hormone expression and relevant factors in female centenarians in Hainan, China / 中南大学学报(医学版)

OBJECTIVES@#Gonadal hormone is essential for the health of postmenopausal women, however, few studies have focused on the epidemiological distribution of gonadal hormones in postmenopausal women in very late postmenopausal women. This study aims to investigate and analyze the differences of serum gonadal hormone content and its influential factors among female centenarians in Hainan, China.@*METHODS@#The questionnaire and physical examination data of 741 female centenarians and 401 elderly females in Hainan Province were collected, and venous blood samples were taken to detect the indexes of lipid metabolism, bone metabolism, and gonadal hormone. The differences of gonadal hormones and relavant factors in female centenarians were analyzed and compared.@*RESULTS@#The serum levels of estradiol and progesterone of female centenarians were significantly higher than those of the elderly females (both P<0.001). The serum levels of estradiol and testosterone of ethnic minority centenarians were higher than those in Han nationality (P<0.001), and the serum estradiol and testosterone concentrations were relatively higher when the daily activities were more than 10 min (both P<0.05). Serum estradiol concentration was negatively correlated with apolipoprotein A-I, high density lipoprotein, triglyceride and bone formation markers such as calcium, inorganic phosphorus and vitamin D3, and was positively correlated with the special sequence of β-collagen (markers of bone resorption) (all P<0.01).@*CONCLUSIONS@#For the extremely late postmenopausal women (such as centenarians), there may be characteristic expressions of gonadal hormones, especially estradiol. There is an unprotective correlation of serum estradiol with lipid metabolism index and bone metabolism index in female centenarians, so it is necessary to evaluate the estrogen content and the use of estrogen therapy in postmenopausal women.

Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter- ference-induced chronic masseter hyperalgesia in ovariectomized rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats.@*METHODS@#In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot.@*RESULTS@#Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased (P < 0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups (P < 0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant (P < 0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant (P>0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups (P < 0.05).@*CONCLUSION@#High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.

Effects of ginger-partitioned moxibustion on the expression levels of PGF2α, E2, P, and mRNAs of PGF2αR and E2R in rats with primary dysmenorrhea due to cold-dampness stagnation / 针灸推拿医学（英文版）

Objective: To observe the effects of ginger-partitioned moxibustion at Shenque (CV8) and Guanyuan (CV4) on the expression levels of endocrine-related molecules and their receptors in rats with primary dysmenorrhea (PD) due to cold-dampness stagnation, thus to explore their analgesic mechanisms. Methods: Thirty-two female Wistar rats were divided into a normal group, a model group, a ginger-partitioned moxibustion group, and a Western medicine group according to the random number table method, with 8 rats in each group. Except for rats in the normal group, all other rats were treated with oxytocin combined with ice-water bath to establish the rat models of PD due to cold-dampness stagnation. After successful modeling, rats in the normal group and the model group did not receive treatment; rats in the ginger-partitioned moxibustion group received treatments with ginger-partitioned moxibustion at Shenque (CV8) and Guanyuan (CV4); rats in the Western medicine group received ibuprofen by intragastric administration. The writhing response of rats was compared among groups, and the serum levels of prostaglandin F2α (PGF2α), estrogen (estradiol, E2), progesterone (P), and the mRNA expression of PGF2α and E2 receptors in the uterine tissues were detected. Results: No writhing behavior was observed in the normal group; compared with the normal group, the serum PGF2α and E2 levels in the model group were increased (P<0.01), while the P level was decreased (P<0.01), and the mRNA expression levels of the uterine PGF2α and E2 receptors were increased (P<0.01, P<0.05). Compared with the model group, the writhing behavior latency was prolonged, and the writhing response score was decreased in the ginger-partitioned moxibustion group and the Western medicine group (P<0.01); the serum PGF2α and E2 levels in the ginger-partitioned moxibustion group and the Western medicine group were decreased, while the P level was increased (P<0.05 or P<0.01); the mRNA expression levels of the uterine PGF2α and E2 receptors in the ginger-partitioned moxibustion group and the Western medicine group were decreased (P<0.05). Compared with the Western medicine group, the ginger-partitioned moxibustion group showed a prolonged writhing behavior latency, reduced writhing response score (P<0.05), and decreased serum E2 level (P<0.05), while no statistical differences in the serum PGF2α and P levels, or the mRNA expression levels of uterine PGF2α and E2 receptors (P>0.05).Conclusion: The analgesic effect of ginger-partitioned moxibustion on PD due to cold-dampness stagnation may be related to regulating the mRNA expression levels of PGF2α and E2 receptors in the uterine tissues.

Role of BDNF/TrkB signaling pathway in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats / 中华麻醉学杂志

Objective:To evaluate the role of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.Methods:Eighty 7-day-old clean-grade healthy newborn Sprague-Dawley rats of both sexes, weighing 11-17 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), 17β estradiol plus propofol group (EP group) and 17β estradiol plus propofol plus BDNF/TrkB signaling pathway blocker K252a group (K group). Propofol 80 mg/kg was intraperitoneally injected every day for 5 days in P, EP and K groups.The equal volume of fat emulsion was given instead in group C. In EP and K groups, 17β estradiol 600 μg/kg was subcutaneously injected at 30 min before propofol injection.BDNF/TrkB signaling pathway blocker K252a 100 μg/kg was intraperitoneally injected in group K. Morris water maze test was performed on days 30-34 after birth to assess the cognitive function.The rats were sacrificed after the end of Morris water maze test, and the hippocampal tissues were removed for determination of the apoptosis rate of hippocampal neurons (by flow cytometry), expression of BDNF, p-Trkb and cleaved caspase-3 (by Western blot and immunofluorescence), and expression of Bcl-2 and Bax mRNA (by real-time polymerase chain reaction) and for microscopic examination of the pathological changes in hippocampal CA1 region (with a light microscope). Bax mRNA/Bcl-2 mRNA ratio was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased ( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group P. Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of BDNF and p-TrkB was up-regulated, the expression of cleaved caspase-3 was down-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were decreased( P<0.05), and the pathological changes in hippocampal CA1 region were attenuated in group EP.Compared with group EP, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group K. Conclusions:BDNF/TrkB signaling pathway is involved in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.