Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Factors to Predict Positive Results of Gonadotropin Releasing Hormone Stimulation Test in Girls with Suspected Precocious Puberty

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.

Eficácia da dose reduzida de gonadorelina e diferentes prostaglandinas no protocolo ovsynch em vacas holandesas / Efficacy of decreasing dose of gonadorelin and comparison between different prostaglandins on ovsynch protocol in lactating Holstein cows

Avaliou-se a eficácia da dose de 0,10 ou de 0,25mg de gonadorelina nas taxas de ovulação e de sincronização no protocolo Ovsynch e de 150mcg de D-cloprostenol ou 0,530mg de cloprostenol sódico na regressão do corpo lúteo (CL) de sete dias e de todos os CL. Foram utilizadas 136 vacas lactantes da raça Holandesa, com média de produção de leite de 23,75,8kg/dia, com 138,4±72,0 dias em lactação. As vacas foram distribuídas aleatoriamente em quatro grupos, de acordo com a dose de gonadorelina e o tipo da prostaglandina. As taxas de ovulação e de sincronização foram de 52,9 por cento e 80,9 por cento para 0,10mg de gonadorelina e de 57,4 por cento e 80,9 por cento para 0,25mg de gonadorelina, respectivamente. A taxa de regressão do CL de sete dias foi de 97,1 por cento para o D-cloprostenol e de 97,5 por cento para o cloprostenol sódico. A taxa de prenhez não foi influenciada pelos tratamentos, mas foi influenciada pela taxa de ovulação à primeira aplicação de gonadorelina, 16,0 por cento vs. 6,6 por cento para as vacas que ovularam e não ovularam, respectivamente. Conclui-se que 0,10mg de gonadorelina foi eficiente e ambas prostaglandinas podem ser usadas em protocolos de sincronização da ovulação.

The efficacy of 150mcg D-cloprostenol or 0.530mg cloprostenol sodium on the 7- day corpus luteum (CL) regression rate, and of two doses of gonadorelin, 0.10mg vs. 0.25mg, on the ovulation and synchronization rates during the Ovsynch protocol were evaluated. Lactating Holstein cows (n=136), producing 23.75.8kg milk/d and 138.4±72.0 days in milk were randomly assigned to four groups, according to dose of gonadorelin and prostaglandin type. No effect of the products and doses tested on conception rate were observed. The ovulation and synchronization rates using 0.10mg or 0.25mg of gonadorelin were 52.9 percent and 80.9 percent vs. 57.4 percent and 80.9 percent, respectively. The CL regression rates in cows ovulating after the first GnRH using D-cloprostenol or cloprostenol sodium were 97.1 percent and 97.5 percent, respectively. The pregnancy rate was not affected by treatment, but by ovulation rate after the first injection of GnRH. The pregnancy rates were 16.0 percent and 6.6 percent for ovulated and non ovulated cows, respectively. The results suggest that 0.10mg dose of gonadorelin was efficient and both prostaglandins can be used in synchronization of ovulation protocols.

Tratamento clínico e por reproduçäo assistida na síndrome dos ovários policísticos associada à infertilidade / Clinical treatment and assisted reproduction in infertility associated to polycystic ovaries

A síndrome dos Ovários Policísticos é considerada a forma mais comum de infertilidade por anovulaçäo e de irregularidade menstrual que acomete a mulher no período do menacme. Apresenta formas variadas de tratamento, sendo que a FIV tem sido empregada com grande sucesso na última década. O objetivo do presente estudo foi de apresentar uma revisäo sistemática da literatura médica abordando o tratamento clínico e por FIV, em pacientes anovulatórias portadoras da síndrome dos ovários policísticos

Gonadotropin-releasing hormone testing in premature thelarche.

Premature thelarche (PT) is characterized by isolated breast development in girls prior to 8 years of age. In addition, there is neither growth spurt nor advanced bone age. It has been suggested that luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) alone is adequate to distinguish central precocious puberty from PT. However, LH response to GnRH is greater in infancy than that in childhood. Therefore, gonadotropin response to GnRH in girls with isolated premature breast development in different age group was studied. Thirty-six girls with isolated PT (aged 0.25-8 years) were evaluated. They were classified into 2 groups; aged < 4 years (group A: mean age 1.57 +/- 0.87 years, n = 13) and > or = 4 years (group B: mean age 6.97 +/- 0.94 years, n = 23). Initial evaluation included X-ray bone age, pelvic sonography and GnRH testing. Patients were followed for at least 1 year to confirm that no patient had progression into puberty. Bone ages in both groups were within mean +/- 2 SD in all patients. Pelvic sonography was performed in all patients which revealed no abnormality of ovaries and uterus. Pubertal response to GnRH stimulation is characterized by peak LH of > 20 IU/L or delta LH of > 15 IU/L which is generally greater than peak follicle stimulating hormone (FSH) or delta FSH, respectively. Mean peak LH and delta LH in group A were 13.0 +/- 6.06 and 11.4 +/- 5.92 IU/L whereas those in the group B were 8.5 +/- 4.10 and 6.3 +/- 3.49 IU/L. Therefore, LH response to GnRH in group A was significantly higher than that in group B (p < 0.05). In addition, the mean peak FSH and delta FSH in group A were 120.5 +/- 45.87 and 109.9 +/- 42.09 IU/L whereas those in the group B were 48.7 +/- 24.05 and 39.9 +/- 23.69 IU/L. Therefore, FSH response to GnRH in group A was significantly greater than that in group B (p < 0.001). LH response to GnRH alone can distinguish prepuberty from puberty in girls > 4 years of age. However, in prepubertal young girls with PT aged < 4 years, pubertal LH response can occur, i.e. peak LH > 20 IU/L. Hence, the greater FSH response to GnRH than that of LH would confirm the diagnosis of premature thelarche in this group. Therefore, the evaluation of FSH response to GnRH is beneficial to distinguish puberty from prepuberty in young girls.

Ovarian activity before and after gonadal suppression by GnRH-a in patients with polycystic ovary syndrome, hyperandrogenism, hyperinsulinism and acanthosis nigricans

Objective. To investigate the ovarian activity before and after gonadal suppression with GnRH-analog in patients with PCO, hyperandrogenism, hyperinsulinism and ancathosis nigricans. Design: Controlled clinical study. Setting: Tertiary academic medical center. Patients: Six patients with clinical findings of PCO, hirsutism and acanthosis nigricans. Interventions. Morning blood samples in the follicular phase to determine the seteroid levels, glucose and insulin curve, comparing to a control group. Administration for 2 consecutive months of a GnRH-analog, comparing, in the study group, the free testosterone levels before and after ovarian suppression. Main Outcome Measure. Determination of insulin levels in PCO, hirsutism and acanthotic patients and the free-testosterone levels before and after gonadal suppression. Results. Insulin levels were significantly higher in the study group when compared to normal women during the glycemic test. We also found a significant decrease in the free-testosterone levels after 2 months of gonadal suppression with GnRH-analog when compared to the initial time. Conclusions. Patients with PCO, hirsutism and acanthosis nicrigans present high levels of in sulin, suggesting an ovarian hyperesponsiveness, which is not sustained when gonadotrophic blockage was achieved.

Daño hipotálamo-hipófiso-gonadal en adolescentes con varicocele / Hypothalamus-pituitary-gonadal damage in adolescents with varicocele

La prevalencia de varicocele (VC) clínico es del 6 por ciento a los 10 años y de 16 por ciento a los 19 años. Nuestro objetivo fue determinar si el grado de varicocele o la diferencia del volumen testicular se correlacionaban con los niveles basales y la respuesta de gonadotrofinas a su factor liberador (LHRH) en 55 adolescentes con varicocele grado (G) 2 a 3 (Dubin-Amelar modificada), edad media 14,0 años (rango: 10-16,8), en estadios de Tanner I, n:2; II, n:9; III, n:15; IV, n:22, V, n:7. Se realizó orquidometria por Prader, dosaje de testosterona basal y de LH y FSH basal, 30 y 60 minutos post 100 mug de LHRH. Se halló varicocele G: 2, n: 9; G: 3, n:40; bilateral, n: 6, hallándose correlación entre el grado de varicocele izquierdo y el área bajo la curva de LH post LHRH en los pacientes con Tanner IV-V, r:0.045. Se encontró asimetría testicular en 33 niños (60 por ciento), siendo el volumen testicular izquierdo de 77,4 + 9,6 por ciento (x + DS con respecto al derecho. La respuesta de LH al LHRH fue más elevada (p<0,05) en los pacientes con volumen testicular izquierdo menor de 80 por ciento con respecto al derecho. El hallazgo de mayor respuesta de la LH al LHRH en nuestros adolescentes con mayor alteración del volumen testicular izquierdo sugiere la presencia de alteración temprana de la función testicular, enfatizando la importancia de estos dos factores en la decisión de la corrección quirúrgica del varicocele.

Telarquia prematura: aumento de la actividad estrogénica total en el plasma / Premature thelarche: increased of total estrogenic activity in the serum

Con el propósito de estudiar las causas de la telarquia prematura, se comparó el perfil hormonal y las características de los genitales internos mediante ultrasonografía pelvians en 41 niñas afectadas, de 21,15 ñ 9,74 meses de edad y e 31 controles de la misma edad y nivel socioeconómico y se buscó contaminación de los alimentos con zearalenona y dietilbestrol por cromatografía en capa delgada. La actividad estrogénica total en el plasma de las niñas, así como plasma y tejidos de pollo, se midió por el método de radiorreceptor. Las concentraciones basales de LH, FSH, prolactina y estradiol eran similares en pacientes y controles. La actividad estrogénica total fue significativamente mayor en las niñas con telarquia (201 ñ 102 vs 78 ñ 20 pg E2 equivalente) y descendió a niveles similares que en los controles (75 ñ 8 pg E2) al desaparecer la telarquia. La respuesta a LHRH en pacientes con telarquia fue mayor para FSH (28,7 ñ 17,5 Uµ/ml) que para LH (5,01 ñ 2,7 Uµ/ml). El tamaño del útero y la maduración ósea fueron similares en ambos grupos, pero el volumen ovárico medio fue mayor en pacientes con telarquia. No se detectaron contaminantes exógenos en la sangre de las niñasy los tejidos de 25 pollos. La actividad estrogénica en el plasma de las aves cumplía las recomendaciones internacionales (FAO). La respuesta de FSH al factor liberador, el mayor volumen ovárico y el aumento de la actividad estrogénica sugieren activación parcial del eje hipotálamo-hipofisiario-gonadal de predominio FSH en las niñas con telarquia prematura

Espaniomenorreia: estudo do perfil gonadotropico / Oligomenorrhea: study of gonadotropic pattern

Foram estudadas 108 pacientes portadoras de espaniomenorreia e 8 mulheres normais determinando-se os valores das dosagens basais de PRL, FSH e LH, e os quocientes FSH/LH e LH/FSH. As pacientes foram divididas em 5 grupos: 1) Total, compreendendo todas as pacientes; 2) A, todas com exclusao daquelas com hiperprolactinemia; 3) B, todas com exclusao das pacientes com valores elevados de FSH; 4) C, todas com exclusao daquelas com valores elevados de LH; 5) D, todas com exclusao das pacientes com valores elevados de PRL, FSH ou LH. Os resultados foram comparados com o grupo normal. Os resultados pareceram indicar que as pacientes com espaniomenorreia: a) produzem mais FSH e LH do que as mulheres normais; b) apresentam hiperprolactinemia em 24 por cento dos casos; c) tem quociente LH/FSH elevado.

Determinaciones hormonales y biopsia de testículo en el varón estéril / Testicular biopsy and hormonal studies in sterile males

Se estudiaron 25 varones que fueron referidos por esterilidad. Estos pacientes tenian un mínino de 2 espermatobioscopías que mostraron oligospermia severa o azoospermia. Se realizaron determinaciones hormonales basales de hormonas luteinizante (LH), folículo-estimulante (FSH), prolactina (PRL) y testosterona (T), sometiéndolos posteriormente a biopsia unilateral de testículo. Como grupo control , se hicieron determinaciones basales de FSH, LH, PRL y T en 35 varones normales de 18-35 años de edad con fertilidad comprobada en los 3 años previos al estudio. La imagen histológica más frecuente fue detención de la maduración (DM) que se encontró en 6/8 oligospérmicos y en 10/17 azoospérmicos, asociada con mínimas alteraciones del patrón hormonal. En 5 pacientes se encontró ausencia de células germinales en 1/8 oligospérmicos y en 4/17 azoospérmicos, y sólo un paciente azoospérmico presentó un incremento de FSH mayor que el doble de la máxima normal de la concentración basal. Cuatro pacientes, 1/8 oligospérmicos y 3/17 azoospérmicos tuvieron esclerosis tubular y peritubular (ETP), los 4 pacientes tuvieron FSH elevada y 2 de los pacientes azoospérmicos tuvieron también niveles elevados de LH y bajos de testosterona. En ambos grupos, oligospérmicos y azoopérmicos, las determinaciones de PRL estuvieron dentro de límites normales. Se concluye que la hiperprolactinemia no es una causa frecuente de oligospermia o azoospermia; las determinaciones basales de FSH, LH y T son útiles para estimar el grado de lesión y las líneas celulares afectadas. La biopsia de testículo constituye un auxiliar útil en la evaluación del pronóstico de algunos pacientes