Acciones óseas de las hormonas de la neurohipófisis / Bone actions of neuro hypophyseal hormones

La oxitocina (OXT) como la arginina-vasopresina (AVP) son dos hormonas primitivas secretadas por la hipófisis posterior. Sus receptores están mucho más ampliamente distribuidos en el organismo de lo que se pensaba originalmente, incluido el hueso. En los estudios preclínicos, la OXT ha mostrado ser anabólica para el hueso, promoviendo la osteogénesis sobre la adipogénesis y favoreciendo la actividad osteoblástica sobre la osteoclástica. Tanto los osteoblastos como los osteoclastos tienen receptores para la OXT, y los efectos de los estrógenos sobre la masa ósea en ratones está mediada por lo menos en parte por la OXT. El mecanismo preciso por el cual la activación de los receptores de oxitocina (OXTR) se traduce en un incremento de la formación ósea permanece poco claro. La AVP también podría afectar el esqueleto en forma directa. Dos de los receptores de la AVP, V1a y V2 están expresados en osteoblastos y osteoclastos. La inyección de AVP en ratones de tipo salvaje aumenta la formación osteoclastos que producen resorción y reduce los osteoblastos formadores de hueso. En forma opuesta, la exposición de precursores osteoblásticos a antagonistas de los receptores V1a o V2, incrementan la osteoblastogénesis, como también lo hace la deleción genética del receptor V1a. (AU)

Both oxytocin (OXT) and argininevasopressin (AVP) are primitive hormones secreted by the posterior pituitary gland. OXT receptors are much more widely distributed in the body than originally thought, including in bone. In preclinical studies, OXT has been shown to be anabolic for bone, promoting osteogenesis over adipogenesis and favoring osteoblastic over osteoclastic activity. Both osteoblasts and osteoclasts have receptors for OXT, and the effects of estrogen on bone mass in mice is mediated at least in part by OXT. The precise mechanism by which the activation of oxytocin receptors (OXTRs) results in an increase in bone formation remains unclear. AVP could also have direct actions on the skeleton. The two AVP receptors, V1a and V2, are expressed in osteoblasts and osteoclasts. Injection of AVP in wild-type mice increases the formation of osteoclasts increasing bone resorption, and reduces bone-forming osteoblasts. On the contrary, the exposure of osteoblastic precursors to V1a and V2 antagonists increase osteoblastogenesis, the same as the genetic deletion of the V1a receptor. (AU)

A influência da ocitocina e do antagonista do receptor de ocitocina no metabolismo ósseo, estresse oxidativo, padrões da marcha e análise do tipo ansioso de ratas senescentes / The influence of oxytocin and the oxytocin receptor antagonist on bone metabolism, oxidative stress, gait and analysis of the anxious type of senescent rats

O objetivo deste estudo foi avaliar a ação da ocitocina (OT) endógena, bem como o efeito potencializador da OT exógena sobre o metabolismo ósseo, estresse oxidativo, marcha e análise do tipo ansioso de ratas na periestropausa. Ao completar 19 meses, os animais receberam injeções de solução salina (0,15M/ip), Atosiban (AT) (At; 300 µg/Kg/ip), OT (Ot; 134 µg/Kg/ip) ou At+Ot (injeções de OT 5 minutos após AT), sendo duas injeções de cada substância por dia, com intervalos de 12 horas entre elas, a cada 30 dias até a idade de 21 meses. Após trinta dias sem tratamentos, foi realizada a coleta de amostras biológicas. Aspartato aminotransferase (AST), marcador de dano hepático, foi menor em Ot e At+Ot. Substância ácida reativa ao ácido tiobarbitúrico (TBARs É¥mol/L), marcador do dano oxidativo lipídico, foi maior no grupo Ot comparado ao At (p = 0,0093), e menor no At+Ot em relação ao Ot (p = 0,0040). Houve maior defesa antioxidante enzimática avaliada por meio da superóxido dismutase (SOD) no grupo Ot em comparação ao Veh (p < 0,0312). Por sua vez, no grupo At houve maior atividade enzimática da fosfatase alcalina (FAL) em relação ao Veh e Ot (p < 0,0001; At+Ot: p = 0,0015). A espessura do tecido ósseo compacto foi menor no grupo At em relação ao Veh (p = 0,0228), no entanto, foi maior no grupo Ot em relação ao Veh e At (p = 0,0132, p < 0,0001); no grupo At+Ot foi menor quando comparado ao grupo Ot (p = 0,0003). O número de trabéculas ósseas foi menor no grupo At comparado ao Veh (p = 0,0240), e maior em Ot em relação ao At (p = 0,0084). Quanto a análise imunoistoquímica realizada no osso cortical do colo do fêmur, o grupo Ot apresentou maior expressão de osteocalcina (OCN) em comparação aos grupos Veh e At (p = 0,05 e 0,0033), e menor expressão no grupo At+Ot em relação ao grupo Ot (p = 0,05). A expressão de fosfatase ácida resistente ao tartarato (TRAP) foi menor no grupo Ot comparado aos grupos Veh e At (p = 0,05 e 0,0033), contudo foi maior no grupo At+Ot comparado ao Ot (p = 0,05). A densidade mineral óssea areal (DMO) foi significativamente maior nos grupos Ot e At+Ot em relação à Veh (p < 0,0001) e grupo At (p = 0,0231, p = 0,0418). Por sua vez, a relação mineral-matriz (vPO4/Proline) foi maior e a substituição de carbonato tipo B (CO3/vPO4) foi menor no grupo Veh. O teste de deambulação por comprimento (cm) usado para avaliar função musculoesquelética, aumentou em última análise no grupo Ot em relação ao grupo Veh - F (p = 0,0078), At - F (p = 0,0023), bem como aumentou sobre Ot - I (p = 0,0094). O teste do labirinto, usado para estudar o comportamento chamado "tipo ansioso", demonstrou que a OT inverte a redução nas entradas dos braços fechados, reduz o tempo gasto no centro causado pelo At. Os resultados obtidos neste estudo demonstram que a OT ajuda a modular o ciclo de remodelação óssea de ratas senescentes, melhorando os parâmetros de densitometria óssea e os parâmetros funcionais musculoesquelético(AU)

The objective of this study was to evaluate the endogenous oxytocin (OT) action, as well as the potentiating effect of exogenous OT on the bone metabolism, oxidative stress, gait and analysis of the anxious type of rats in periestropause. Upon completing 19 months, the animals received injections of saline solution (0.15M/ip), Atosiban (AT) (At; 300 µg/Kg/ip), OT (Ot; 134 µg/Kg/ip) or At+Ot (OT injections 5 minutes after AT), being two injections of each substance per day, with intervals of 12 hours between them, every 30 days until the age of 21 months. After thirty days without treatment, biological samples were collected. Aspartate aminotransferase (AST), a marker of liver damage, was lower after Ot and At+Ot. Acid reactive substance to thiobarbituric acid (TBARs µmol/L), marker of lipid oxidative damage, was higher in the Ot group compared to At (p = 0.0093), and lower in At+Ot compared to Ot (p = 0.0040). There was a higher antioxidant enzymatic defense evaluated by means of superoxide dismutase (SOD) in the Ot group compared to Veh (p < 0.0312). In turn, in the At group there was greater alkaline phosphatase (FAL) enzymatic activity in relation to Veh and Ot (p < 0.0001; At+Ot: p = 0.0015). The thickness of the compact bone tissue was smaller in the At group in relation to Veh (p = 0.0228), however, it was greater in the Ot group in relation to Veh and At (p = 0.0132, p < 0.0001); in the At+Ot group it was smaller when compared to Ot (p = 0.0003). The number of bone trabecules was smaller in the At group compared to the Veh (p = 0.0240), and greater in Ot in relation to the At (p = 0.0084). As for the immunohistochemical analysis performed on the cortical bone of the femoral neck, the Ot group presented a higher expression of osteocalcin (OCN) compared to the Veh and At groups (p = 0.05 and 0.0033), and lower expression in the At+Ot group compared to the Ot group (p = 0.05). The tartrate-resistant acid phosphatase (TRAP) expression was lower in the Ot group compared to the Veh and At groups (p = 0.05 and 0.0033), however it was higher in the At+Ot group compared to Ot (p = 0.05). The sandal mineral density (BMD) was significantly higher in the Ot and At+Ot groups compared to Veh (p < 0.0001) and At group (p = 0.0231, p = 0.0418). In turn, the parent mineral ratio (vPO4/Proline) was higher and the replacement of carbonate type B (CO3/vPO4) was lower in the Veh group. The walking test per length (cm) used to evaluate musculoskeletal function was ultimately increased in group Ot in relation to group Veh - F (p = 0.0078), At - F (p = 0.0023), as well as increased over Ot - I (p = 0.0094). The labyrinth test, used to study the so-called "anxious type" behavior, demonstrated that the OT reverses the reduction in the entries of the closed arms, reducing the time spent in the center caused by At. The results obtained in this study show that the OT helps to modulate the cycle of bone remodeling of senescent rats, improving the parameters of bone densitometry and the musculoskeletal functional parameters(AU)

No Association between Polymorphisms of Vitamin D and Oxytocin Receptor Genes and Autistic Spectrum Disorder in a Sample of Turkish Children

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. METHODS: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Başkent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. RESULTS: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. CONCLUSION: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey.

Oxytocin produces thermal analgesia via vasopressin-1a receptor by modulating TRPV1 and potassium conductance in the dorsal root ganglion neurons

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by d(CH₂)₅[Tyr(Me)²,Dab⁵] AVP, a vasopressin-1a (V1a) receptor antagonist, but not by desGly-NH₂-d(CH₂)₅[DTyr², Thr⁴]OVT, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.

Cloprostenol administration in the first week postpartum reduces expression of oxytocin receptors in the endometrium in Holstein-Zebu cows / Administração de cloprostenol na primeira semana pós-parto pode reduzir a expressão de receptores de ocitocina no endométrio de vacas mestiças Holandês-Zebu

The present study investigated the hormonal profile and expression of prostaglandin F2α (PGF2α), oxytocin and estrogen receptors in uterine tissues of postpartum cows treated with cloprostenol. Twenty Holstein-Zebu crossbred cows were treated with saline solution (treatment CONT) or cloprostenol (treatment CLO), both administered two and five days postpartum. Blood samples were collected on days two, seven, 14, 21 and 28 postpartum for progesterone, PGF2α metabolite (PGFM) and estradiol determination, and endometrial biopsy was performed in order to quantify the expression of oxytocin receptor (OXTR), prostaglandin F receptor (PTGFR) and estrogen receptor 1 (ERS1) genes. In the CLO treatment, expression of OXTR was reduced (P<0.05) but no difference (P>0.05) between treatments was found for PTGFR and ERS1 expression. Estrogen concentrations increased progressively until day 14 (P<0.05) and the highest OXTR expression and lowest PTGFR expression were observed on day 14 (P<0.05) in both treatments. Serum PGFM concentrations were high throughout the experiment. In conclusion, cloprostenol administration at days two and five of postpartum seems to reduce OXTR expression in the endometrium in crossbred cows.(AU)

O presente estudo avaliou o perfil hormonal e a expressão gênica de receptores de prostaglandina F2α (PGF2α), ocitocina e estrógeno no endométrio de vacas pós-parto tratadas com cloprostenol. Vinte vacas mestiças Holandês-Zebu foram tratadas com solução salina (tratamento CONT, n = 10) ou cloprostenol (tratamento CLO, n = 10), ambos administrados dois e cinco dias após o parto. Amostras de sangue foram coletadas nos dias dois, sete, 14, 21 e 28 pós-parto para mensuração de progesterona, de metabólito de PGF2α (PGFM) e de estradiol, e foram obtidas biópsias endometriais para quantificar a expressão de PTGFR, OXTR e ESR1. No tratamento CLO, a expressão gênica de receptores de ocitocina foi menor (P<0,05). As concentrações de estrógeno aumentaram progressivamente até o dia 14 (P<0,05). A maior expressão de OXTR foi observada no dia 14 (P<0,05). A expressão de ESR1 foi semelhante entre os tratamentos (P>0,05). Os níveis de PGFM foram altos durante todo o estudo. Conclui-se que a administração de cloprostenol nos dias dois e cinco pós-parto parece diminuir a expressão de OXTR no endométrio em vacas mestiças.(AU)

Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs.

The role of oxytocin in cardiovascular regulation

Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions.

Correlatos neurobiológicos de la intervención psicoterapéutica / Neurobiological Correlates of Psychotherapeutic Intervention

Los avances en neurociencia permiten profundizar la comprensión de los correlatos neurobiológicos de las diferentes intervenciones psicoterapéuticas. Con el objetivo de presentar un panorama abarcativo de esta temática, se presentan estudios que dan cuenta de los efectos neurales de las psicoterapias, y que se enfocan en las diferentes áreas cerebrales involucradas y los posibles mecanismos subyacentes en los diferentes niveles, incluyendo tanto los moleculares como los que están relacionados con modificaciones en los circuitos. El artículo contiene también, una referencia a los procesos de memoria que podrían estar vinculados con los efectos de las psicoterapias. Se realiza una breve referencia a la comunicación empática, y a la neurobiología del apego, procesos posiblemente involucrados también en el trabajo psicoterapéutico, incluyendo una mención al rol de la oxitocina. Dada la importancia que en los últimos años ha adquirido el concepto de epigénesis y la posibilidad de que la eficacia de las psicoterapias pueda ser incrementada a través de la aplicación de fármacos moduladores de eventos epigenéticos, se incluye también una referencia a estos hallazgos

Advances in neuroscience allow to deepen the understanding of the different psychotherapeutic interventions and its neurobiological correlations. With the aim of presenting a comprehensive overview of this topic, studies that focus on the neural effects of psychotherapies, the different brain areas involved on it and the possible underlying mechanisms at different levels, including both the molecular as those that are linked to changes in the cicuits, are presented. The article also includes a reference to the processes of memory that could be linked with the effects of psychotherapies. it's also made a brief reference to empathic communication and the neurobiology of attachment, processes possibly also involved in psychoterpaeutic work, including a mention of the role of oxytocin. Given the importance that has acquired the concept of epigenesis and the possibility that the effectiveness of pscychotherapies could be increased through the application of modulating drugs of epigenetic events in recent years, a reference to these findings was also included

Reducing creatine kinase-MB levels following oxytocin administration during ischemia-reperfusion periods in isolated rat heart

Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide [NO], prostacyclin and mitochondrial ATP-dependent potassium channels in this regard. Male wistar rats [n=8] were anesthetized with sodium thiopental and their hearts were transferred to a Langendorff perfusion apparatus. All animals were randomly divided into nine groups as follow; in the ischemia-reperfusion group, hearts underwent 30 min of regional ischemia followed by 120 min of reperfusion. In oxytocin group, hearts were perfused with oxytocin 5 min after ischemia induction for 25 min. In other groups, 35 min prior to oxytocin perfusion, atosiban [a non-specific oxytocin receptor blocker], L-NAME [an NO synthase inhibitor], indomethacin [a non-specific cyclooxygenase blocker] and 5-HD [a specific mKATP channel blocker] were perfused for 10 min. In all groups, we measured CK-MB levels in the coronary effluent at the end of reperfusion. Moreover, coronary flow [mL/min] was measured at baseline, during ischemia period and 60 and 120 min after reperfusion. Oxytocin administration significantly reduced CK-MB level in oxytocin group as compared to ischemia-reperfusion group. Administration of atosiban, L-NAME, indomethacin and 5-HD prior to oxytocin perfusion abolished the effects of oxytocin on CK-MB levels. Administration of oxytocin during ischemia and reperfusion periods deceased CK-MB levels but infusion of atosiban, L-NAME, 5-HD and indomethacin inhibited oxytocin from exerting its effects

Neuropeptide oxytocin and male infertility / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze the level of the oxytocin (OT) and the expression of oxytocin receptor (OTR) in males with idiopathic infertility.</p><p><b>METHODS</b>Sixty-five infertile males aged 20 -45 years were divided according to their semen parameters into an idiopathic oligozoospermia group (OG, n = 20), an idiopathic asthenozoospermia group (AG, n = 25), and an idiopathic oligoasthenozoospermia group (OAG, n = 20). Another twenty 20-45 years old healthy male volunteers with a natural childbearing history were included in the control group (CG). All the subjects were detected for the contents of luteinizing hormone (LH), follicle stimulating hormone (FSH) , testosterone (T) and OT, and analyzed for the expression of OTR by sequencing the functional region of the OTR promoter (OTRP), OTR-mRNA, and OTR-COOH terminus. The gene sequences were compared using DNASTAR-MegAlign, Western blot values changed into enumeration data, and all the data analyzed by one-way ANOVA and Dunnette's multiple range t-test.</p><p><b>RESULTS</b>A significantly lower content of OT was observed in CG ( [79.30 +/- 3.83] pg/ml) than in OG ([118.53 +/- 7.69] pg/ml, AG ([108.81 +/- 5.66] pg/ml) and OAG ([103.71 +/- 4.54] pg/ml) (F(0.05/2[2,82]) = 8.29, P < 0.01). The content of LH was significantly lower in AG ([4.26 +/- 0.31] IU/L) and OAG ([4.55 +/- 0.40] IU/L) than in OG ([6.77 +/- 0.57] IU/L) and CG ([7.19 +/- 0.50] IU/L) (F(0.05/2 [2,82]) = 11.64, P < 0.01), and so was the content of FSH in AG ( [5.02 + 0.39] IU/L) than in CG ([8.91 +/- 0.91] IU/L), OG ([11.86 +/- 1.76] IU/L) and OAG ([8.82 +/- 1.03] IU/L) (F(0.05/[2,82]) = 7.22, P < 0.01). There were no significant differences in the T content among the four groups (F(0.05/2[2,82] = 0.42, P = 0.739). No evident gene mutation was found in OTRP and OTR-mRNA gene sequencing. Human OTRs in the lymphocytes were monomers and oligomers, mostly tetramers and hexamers. There were obviously more monomers in AG (0.41 +/- 0.03) and OAG (0.13 +/- 0.01) than in OG (0.05 +/- 0.004) and CG (0.05 +/- 0.003) (F(0.05/2[2,82]) = 115.50, P < 0.01), while the number of oligomers was markedly decreased in 20% of the cases in AG.</p><p><b>CONCLUSION</b>Significant differences in the content of OT and expression of OTR between fertile and infertile men suggested an association of OT with male infertility. The decreased expression of OTR oligomers and increased expression of monomers may be related to idiopathic asthenozoospermia, which has provided a new insight into the pathogenesis and treatment of male infertility.</p>

Study on effects of acupuncture on mice dysmenorrhea model and the mechanism / 中国针灸

<p><b>OBJECTIVE</b>To probe the mechanism of acupuncture in treatment of dysmenorrhea.</p><p><b>METHODS</b>Adult mice with no pregnancy were randomly divided into a normal group, a model group, an acupuncture group and a medication group. The model group, the acupuncture group and the medication group were modeled by Diethylstilbestrol and Ocytocin. For the acupuncture group, at the 7th day of modeling, acupuncture was given at "Sanyinjiao" (SP 6), "Diji" (SP 8), once a day, for 5 days; and at the 7th day of modeling, Yimucao Gao 0.6 mg/g was given intragastrically to the medication group for 5 days. The stretching latent period and the number of stretching within 30 min were observed, and mRNA levels of ocytocin receptor (OctR) and vasopressin receptor (VasR) in the uterus tissue were detected with RT-PCR method.</p><p><b>RESULTS</b>Compared with the model group, the stretching latent period extended (P < 0.05) and the number of stretching within 30 min significantly decreased (P < 0.05); and there were significant differences in the mRNA levels of ocytocin receptor and vasopressin receptor in the uterus tissue in the model group as compared with those in other 3 groups (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Acupuncture can improve the dysmenorrheal symptom to a certain extent, and the mechanism is possibly related to regulative effects of acupuncture on hormones-mediating receptors in mice.</p>

Influence of Cx43 on acupuncture effect on the primary dysmenorrheal rat / 中国针灸

<p><b>OBJECTIVE</b>To observe the influence of silencing Connexin43 (Cx43) expression of partial acupoints on acupuncture effect, so as to probe into the mechanism of acupuncture treatment for primary dysmenorrhea.</p><p><b>METHODS</b>The primary dysmenorrheal rat model made by oxytocin and RNA interference (RNAi) technology was used to silence the expression of Cx43 in acupoints. Fifty SD female rats were divided into five groups, a normal group (N), a model group (M), an acupuncture group (A), an acupuncture plus interference group (A+I), an acupuncture plus interference control group (A+IC). RT-PCR method was used to observe the oxytocin receptor (OTR) and vasopressin receptor (VPR) mRNA expressions in the uterus in each group. Plasma prostaglandin E2 (PGE2) and PGF2alpha levels were detected by radioimmunoassay and ELISA, respectively.</p><p><b>RESULTS</b>(1) The times of writhing body (9.43 +/- 3.87 and 10.28 +/- 4.23) were significantly lower and the latency period of writhing body (12.43 +/- 3.46, 11.00 +/- 3.65) were longer in the group A and the group A+IC as compared with (15.43 +/- 5.13, 17.00 +/- 3.87) and (7.57 +/- 1.99, 8.43 +/- 2.57) in the group M and group A+I (P < 0.05), respectively. (2) The levels of Cx43 mR NA level and protein expression of acupoint in the group A+I were significantly lower than those of the group N (P < 0.05). (3) OTR and VPR mRNA in the uterus in the group A and the group A+IC were significantly lower than those in the group M and the group A+I (P < 0.05), with no significant difference between the group M and the group A+I (P > 0.05). (4) As compared with the group M, PGE2 level increased and PGF2alpha level decreased in the group A and the group A+IC (P < 0.05).</p><p><b>CONCLUSION</b>Silencing Cx43 expression of partial acupoint can inhibit effectively the effect of acupuncture through decreasing OTR and VPR in endometrium of the dysmenorrheal rat and adjusting the prostaglandins (PGs) synthesis system, which possibly is one of the mechanisms of acupuncture for treatment of primary dysmenorrhea.</p>

G-protein coupled receptors & autism -- reflections on a double-edged sword at the example of the oxytocin receptor system.

G-protein coupled receptors (GPCR) tend to desensitize/internalize when exposed to excess agonist.Previously, we have supported the argument that in the case of the oxytocin receptor (OTR), excess agonist (oxytocin, OT) at birth could be implicated with behavioural disorders of the autistic spectrum. In this review, more recent evidence for this hypothesis is summarized, and it is juxtaposed against reports where exogenous OT was found beneficial in alleviating certain undesired behaviours. Facing this dichotomy, we suggest possible in silico drug discovery approaches to mitigate undesired side effect of OT administration/OTR desensitization, especially in the light of potentially emerging agonist therapies. For this, the most important structural features of OTR are reviewed, and we highlight here the need for higher level of theory studies at the easier approachable extracellular receptor side, where loop 3(e3) and the N-terminated strain of OTR appear to offer targets of particular interest for the development of an agent that conditions the action of excess OT. Another approach, based on the development of new agonists with an improved receptor activation to receptor phosphorylation ratio, is also discussed. Finally, the issue of OTR desensitization is put into the broader context of GPCR desensitization and possible implications for behavioural disorders, and the case is made for the usefulness of computational studies in this area.

uterine relaxant effect of curcumin in rats; an in vitro study

Addition of curcumin in concentrations of 1.4 x 10[-5] M, 2.8 x 10[-5] M and 5.6 x 10 [-5]M to the organ bath, resulted in significant inhibitions in the normal uterine contractions of non-pregnant rats in the diestrus stage. The recorded decreases in frequencies of uterine contractions were 32%, 47% and 67%, while the inhibitions were 50%, 67% and 76% for the amplitude, respectively. The reductions in area under the curve [AUC] of contractions were 67%, 71% and 86% for the added concentrations, respectively. Pretreatment with curcumin in the previous concentrations revealed inhibitory effects on the uterine response to oxytocin [10[-11]M] amounting to 77%, 78% and 72% in AUC with respect to that obtained post-addition of oxytocin alone. These results indicate that the tocolytic potential of curcumin may involve oxytocin receptor-dependent pathway

Neurohypophyseal hormones and atrial natriuretic peptide in the control of body fluid homeostasis

Mammals control the volume and osmolality of their body fluids by stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+-receptors (plasma osmolality or sodium concentration) and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrative response, which depends on the integrity of the anteroventral region of the third ventricle, e.g. organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. In addition, the paraventricular, supraoptic and suprachiasmatic nuclei are also important structures involved in hydromineral balance. The hypothalamo-neurohypophyseal system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and non-osmotic stimuli. The natriuretic factor in the heart, which is released by the distension of the atria, leading to natriuresis and a myorelaxing action on vascular smooth muscle, also contributes to the hydromineral balance. In addition to the natriuretic factor in the heart, the identification of a natriuretic factor in the central nervous system mediating natriuresis was also demonstrated by purification of hypothalamic extracts. Therefore, the presence of the natriuretic factor in the heart and in the central nervous system allowed the characterization of a neuroendocrine system controlling body fluid homeostasis.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

Effects of oxytocin and an oxytocin receptor antagonist on retention of a nose-poke habituation response in mice

The present study describes the use of nose-poke habituation as a memory task in mice and demonstrates that it is sensitive to oxytocin (OT) and an oxytocin receptor antagonist (AOT) administered after the learning trial. Habituation of nose-poke behavior of mice was defined as a reduction in number of nose-pokes compared to baseline, and was measured in a hole-board apparatus to which male Swiss mice were exposed on two consecutive days for 5 min, respectively. Immediate post-training subcutaneous administration of OT (2.00 mug/kg) impaired retention performance, whereas AOT (0.20 mug/kg) enhanced it. Neither the impairing effects of OT (2.00 mug/kg) nor the enhancing effects of AOT (0.20 mug/kg) were seen when the training treatment interval was 180 min, suggesting that both treatments influenced the storage of recently acquired information. The effects of OT (2.00 mug/kg) on retention were prevented by AOT (0.02 mug/kg) administered immediately after training but 10 min prior OT treatment. This dose of antagonist did not affect retention by itself which suggest that impairing effects of OT on retention are probably due to an interaction of the neuropeptide with specific receptors. The actions of OT and AOT on retention were not due to enduring proactive effects of the compounds on performance during the retention test, since when given to untrained mice did not modify their spontaneous activities in the hole-board when recorded 24 h later. We suggest that nose-poke habituation learning can be a suitable method to investigate the mnestic effects of drugs, and that oxytocin negatively modulates memory storage of this form of learning elicited by stimuli repeatedly presented without reinforcement.