La esteroidogénesis en el síndrome de ovarios poliquísticos / Steroidogenesis in polycystic ovary syndrome

Resumen El síndrome de ovarios poliquísticos es la enfermedad endocrina más frecuente en la edad reproductiva; se caracteriza por alteraciones menstruales, hiperandrogenismo clínico o bioquímico e identificación ultrasonográfica de quistes ováricos. Las alteraciones neuroendocrinas y metabólicas que lo acompañan implican desensibilización del eje hipotálamo-hipófisis-ovario, esteroidogénesis e hiperandrogenismo. Recientemente se ha explorado el papel de la resistencia a la insulina. Se ha establecido que la principal causa del síndrome de ovarios poliquísticos es el hiperandrogenismo, debido a alteraciones enzimáticas en la vía esteroidogénica, por lo que existe sobreestimulación por parte de la hormona luteinizante a causa de los pulsos rápidos generados por la hormona liberadora de gonadotropinas. Diversos factores de crecimiento y citocinas inhiben la conversión de andrógenos a estrógenos. En la desregulación característica de este síndrome también están involucradas la activina y las prostaglandinas e, incluso, altos niveles de insulina.

Abstract Polycystic ovary syndrome is the most common endocrine disease in reproductive age, characterized by menstrual alterations, clinical or biochemical hyperandrogenism, and ultrasound-identified ovarian cysts. The neuroendocrine and metabolic alterations that accompany this condition involve the desensitization of the hypothalamus-pituitary-ovary axis, steroidogenesis and hyperandrogenism; recently, the role of insulin resistance has been explored. Hyperandrogenism has been established to be the main cause of polycystic ovary syndrome, due to enzymatic alterations in the steroidogenic pathway that cause luteinizing hormone over-stimulation because of quick pulses generated by gonadotropin-releasing hormones. Various growth factors of and cytokines inhibit the conversion of androgens into estrogens; activin and prostaglandins are also involved, even high levels of insulin participate in the characteristic deregulation of this syndrome.

Avanços na etiologia, no diagnóstico e no tratamento da puberdade precoce central / Advances in the etiology, diagnosis and treatment of central precocious puberty

O início da puberdade caracteriza-se pelo aumento de amplitude e frequência dos pulsos do hormônio secretor de gonadotrofinas (GnRH) após um período de relativa supressão hormonal durante a infância. A reemergência da secreção pulsátil do GnRH resulta em aumento na secreção de gonadotrofinas, hormônio luteinizante (LH) e folículo estimulante (FSH), pela hipófise anterior e consequente ativação gonadal. A ativação prematura do eixo hipotálamo-hipófise-gonadal resulta em puberdade precoce dependente de gonadotrofinas, também conhecida como puberdade precoce central (PPC), e se caracteriza pelo desenvolvimento dos caracteres sexuais secundários antes dos 8 anos nas meninas e 9 anos nos meninos. O início do desenvolvimento puberal provém da interação complexa de fatores genéticos, nutricionais, ambientais e socioeconômicos. O diagnóstico clínico da PPC baseia-se em reconhecimento de desenvolvimento puberal progressivo, concentrações púberes de LH em condição basal e/ou após estímulo com GnRH e avanço de idade óssea. A ressonância magnética de encéfalo é útil no estabelecimento de diagnóstico diferencial entre as formas orgânica ou idiopática. Os análogos de GnRH de ação prolongada representam o tratamento de escolha da PPC. O componente genético da PPC foi recentemente fortalecido pela evidência de mutações no gene MKRN3, localizado no braço longo do cromossomo 15, em crianças com PPC familial. Nessa revisão, dados clínicos e terapêuticos da PPC serão amplamente discutidos, visando à atualização e à conduta criteriosa dessa condição clínica de grande relevância na endocrinologia pediátrica.

The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the pituitary gland, and the consequent activation of gonadal function. Early activation of the hypothalamic–pituitary–gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty (CPP), which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. CPP is diagnosed on the basis of clinical signs of progressive pubertal development before the age of 8 years in girls and 9 years in boys, pubertal basal and/or GnRH-stimulated LH levels, and advanced bone age. Magnetic resonance imaging of the central nervous system is essential for establishing the CPP form as organic or idiopathic. Depot GnRH-analogues represent the first-line of therapy in CPP. Very recently, the genetic component of CPP was demonstrated by the evidence that the deficiency of the MKRN3 gene, located on long arm of chromosome 15, causes familial CPP in humans. In this current review, clinical and therapeutic aspects of the CPP will be discussed, contributing to adequate diagnosis and criterious approach of this relevant condition of pediatric endocrinology.

Regulation of luteinizing hormone receptor in hippocampal neurons following different long-lasting treatments of castrated adult rats.

The aim of this study was to investigate the effects of different Luteinizing hormone (LH) and steroid hormones levels on LH receptor (LHR) expression in the hippocampal cells. Rats (24 males and 24 females) were assigned to four groups: one control and three experimental [gonadectomy (GDX), gonadectomy + gonadotropin releasing hormone analogue (GDX+GnRHa) and GDX+GnRHa+estradiol (E2) or testosterone (T)] independently for each gender. All experimental rats were gonadectomized; then GnRHa was administrated to GDX+GnRHa group, and GnRHa plus steroid hormone to GDX+GnRHa+E2 or T group in both genders for four-month. LHR mRNA expression and its protein level in hippocampal cells were measured using QRT-PCR and Western blotting. Quantification of mRNA revealed a decrease in LHR transcripts level in GDX+GnRHa group of females. A significant change was observed between GDX groups and GDX+GnRHa+E2 or T versus GDX+GnRHa group in females. High levels of LH decreased significantly the immature isoform of LHR in GDX group compared to control group in both genders, but low LH concentrations in GDX+GnRHa group induced immature LHR isoform production only in females. Therefore increased LH concentration induces production of incomplete LHR transcripts in hippocampal cells and decreases immature LHR at the protein level. This implies that LH decreases the efficiency of translation through either producing non-functional LHR molecules or preventing their translation.

Update on the etiology, diagnosis and therapeutic management of sexual precocity: [review]

Precocious puberty is defined as the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Gonadotropin-dependent precocious puberty (GDPP) results from the premature activation of the hypothalamic-pituitary-gonadal axis and mimics the physiological pubertal development, although at an inadequate chronological age. Hormonal evaluation, mainly through basal and GnRH-stimulated LH levels shows activation of the gonadotropic axis. Gonadotropin-independent precocious puberty (GIPP) is the result of the secretion of sex steroids, independently from the activation of the gonadotropic axis. Several genetic causes, including constitutive activating mutations in the human LH-receptor gene and activating mutations in the Gs protein a-subunit gene are described as the etiology of testotoxicosis and McCune-Albright syndrome, respectively. The differential diagnosis between GDPP and GIPP has direct implications on the therapeutic option. Long-acting gonadotropin-releasing hormone (GnRH) analogs are the treatment of choice in GDPP. The treatment monitoring is carried out by clinical examination, hormonal evaluation measurements and image studies. For treatment of GIPP, drugs that act by blocking the action of sex steroids on their specific receptors (cyproterone, tamoxifen) or through their synthesis (ketoconazole, medroxyprogesterone, aromatase inhibitors) are used. In addition, variants of the normal pubertal development include isolated forms of precocious thelarche, precocious pubarche and precocious menarche. Here, we provide an update on the etiology, diagnosis and management of sexual precocity.

A puberdade precoce é definida como o desenvolvimento dos caracteres sexuais secundários antes dos 8 anos nas meninas e dos 9 anos nos meninos. A puberdade precoce dependente de gonadotrofinas (PPDG) resulta da ativação prematura do eixo hipotálamo-hipófise-gonadal e mimetiza o desenvolvimento puberal fisiológico, embora em idade cronológica inadequada. A avaliação hormonal, principalmente os valores de LH basal e após estímulo com GnRH exógeno confirmam a ativação do eixo gonadotrófico. A puberdade precoce independente de gonadotrofinas (PPIG) é o resultado da secreção de esteróides sexuais independentemente da ativação do eixo gonadotrófico. Diversas causas genéticas, incluindo mutações ativadoras constitutivas no gene do receptor do LH humano e mutações ativadoras no gene da subunidade a da proteína G representam as etiologias da testotoxicose e da síndrome de McCune Albright, respectivamente. O diagnóstico diferencial entre PPDG e PPIG tem implicação direta na opção terapêutica. Análogos de GnRH de ação prolongada é o tratamento de escolha da PPDG. A monitorização do tratamento da PPDG é realizada pelo exame clínico, avaliação hormonal e exames de imagem. Para o tratamento da PPIG, são usadas drogas que bloqueiam a ação dos esteróides sexuais nos seus receptores específicos (ciproterona, tamoxifeno) ou bloqueiam a sua síntese (cetoconazol, medroxiprogesterona e inibidores da aromatase). Variantes do desenvolvimento puberal normal incluem as formas isoladas de telarca, pubarca e menarca precoces. Nesta revisão, atualizamos a etiologia, o diagnóstico e tratamento da precocidade sexual.

Efectividad de la terapia con leuprolide acetato de depósito cada tres meses en pubertad precoz central / Effectiveness of Leuprolide acetate therapy every three months in central precocious puberty

Background: Precocious puberty may reduce final adult height, and affected children may suffer social and emotional problems. The efficacy of treatment with a long acting agonist analogue of the gonadotropin releasing hormone (aLHRH) has been well demonstrated. Aim: To evaluated the efficacy of a new formulation of aLHRH (leuprolide, Lupron ®) for the suppression of gonadotropin activation and clinical signs of puberty. Material and methods: Eleven children (ten females) with idiopathic central precocious puberty, with a mean chronological age of 7.5±1.8 years and a bone age of 9.7±1.8 years were recruited. Testicular volume in the male was 15 ml. In females, Tanner stage for breast development was between 2-4 and mean ovarian volume was 2.3±0.8 ml. They were treated during 18 months with aLHRH, 11.25 mg administered intramuscularly every three months. Results: Clinical, hormonal and ultrasonographic signs of puberty regressed in all patients. The degree of suppression of LH was 87.7±5.1% at the end of the 18 months. No significant changes in bone mineral content were observed during the treatment period. Conclusions: Leuprolide (aLHRH) 11.25 mg, injected every three months, is effective for the control of central precocious puberty and allows to reduce the number of yearly injections from 12 to 4.

Hormônio liberador de gonadotrofinas em peixes: aspectos básicos e suas aplicações / Gonadotropin-releasing hormone in fish: basic aspects and its applications / Hormona liberadora de gonadotropinas en peces: aspectos básicos y sus aplicaciones

O objetivo deste trabalho é revisar alguns aspectos relacionados ao estudo do hormônio liberador de gonadotrofinas (GnRH) e sua aplicação na manipulação dos processos reprodutivos em peixes. Esse neurohormônio é um decapeptídeo presente no hipotálamo e em diferentes regiões do cérebro, sendo considerado um dos fatores de maior importância no processo de síntese e liberação das gonadotrofinas pelas células endócrinas da pituitária. O GnRH. apresenta variantes moleculares, podendo estar presente nos peixes em duas ou três formas, as quais, além de estimular os gonadótrofos da pituitária, podem exercer ação sobre somatótrofos e células que expressam prolactina e somatolactina. No últimos anos, diversos estudos têm sido direcionados para o desenvolvimento de metodologias que empregam formas nativas ou sintéticas de GnRH, a fim de manipular os processos reprodutivos em peixes, com relativo sucesso. Contudo novos estudos devem ser realizados para conhecer melhor a neurobiologia dessas moléculas, levando ao desenvolvimento de formas sintéticas, análogas de GnRH (GnRHa) específicas superativas, que apresentem maior atividade biológica. O desenvolvimento de doses mínimas efetivas e de mecanismos de liberação contínua mais eficientes deverá com certeza ser objeto de estudo futuro.

The objective of this work is to review some aspects related to the study ofthe gonadotropin-releasing hormone (GnRH) and its application in the manipulation of the reproductive processes in fish. This neurohormone is a decapeptide present in hypothalamus and in ditIerent regions of the brain, being considered one of the factors of biggest importance in the process of gonadotropin synthesis and release from endocrine pituitary cells. DitIerent GnRH molecular forms had been present in fish in two or three forms, which besides stimulating the pituitary gonadotropins; it can exert some action on somatotropins and cells that express prolactin and somatolactin. In the last years, several studies have been directed to the development of methodologies using native or synthetic forms of GnRH, in order to manipulate the reproductive processes in fish, with relative success. However, new studies must be carried through to get to know the neurobiology of these molecules better, leading to the development of specific and analog forms of super active GnRHa which present greater biological activity. The development of minimum etIective doses and more efficient mechanisms of continuous release will be the objectof a future study.

El objetivo de este trabajo es revisar algunos aspectos relacionados con el estudio de ia hormona liberadora de gonadotropinas (GnRH) y su aplicación en ia manipulación de los procesos reproductivos en peces. Esta neurohormona es un decapeptido presente en el hipotálamo y en diferentes regiones deI cerebro y es considerado como uno de los factores de mayor importancia en el proceso de síntesis y liberación de Ias gonadotropinas por Ias células endócrinas de Ia pituitaria. EI GnRH se presenta como variantes moleculares, pudiendo estar presente en los peces en dos o tres formas, Ias cuales además de estimular los gonadotropos de Ia pituitaria, pueden ejercer acción sobre somatotropos y células que expresan prolactina y somatolactina. En los últimos afios, diversos estudios han sido dirigidos para el desarrollo de metodologías que empleen formas nativas o sintéticas de GnRH, a fin de conducir los procesos reproductivos en peces, con relativo éxito. Sin embargo nuevos estudios deben ser realizados para conocer mejor la neurobiologia de estas moléculas, llevando al desarrollo de formas sintéticas de GnRH específicas, superactivas que presenten mayor actividad biológica. Todavia, el desarrollo de dosis mínimas efectivas y de mecanismos de liberación continua más eficientes, ciertamente será objeto de estudio futuro.

Efecto de la activacion gabaergica sobre la maduracion sexual en ratas hembras peripuberales / Effect prologed gabaergic activation on the pubertal development of female rats

Evaluamos 1) efecto del tratamiento prolongado (días 23-29 postnatales) con ácido aminooxiacético (AAOA) sobre el desarrollo puberal en ratas hembra; este tratamiento aumentó el contenido de GABA (p< 0.002), disminuyendo el de GnRH y glutamato (p < 0.05 y < 0.02) en hipotálamo. La LH (p < 0.05) y el estradiol (p < 0.005) séricos cayeron. La apertura vaginal fue a los 30.8 + 0.6 días en los controles, y a los 36.7 + 0.98 días en las tratadas (p < 0.0001). 2) A los 30 días, el tratamiento agudo con AAOA redujo la liberación ex vivo de GnRH y de glutamato la de taurina. Este efecto fue similar al observado agregando al medio agonistas GABA-A y B. Conclusiones: la activación peripuberal del sistema GABAérgico frena el eje reprodutor, produciendo un retraso en el desarrollo. Esto podría atribuirse a la existencia, en esta etapa, de interrelaciones fisiológicas entre los aminoácidos que regulan la secreción de GnRH (GABA, glutamato, taurina).

The role of nitric oxide in reproduction

Nitric oxide (NO) plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH). The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP). NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS) in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG).

Interaction between NO and oxytocin: influence on LHRH release

Nitric oxide synthase (NOS)-containing neurons have been localized in various parts of the CNS. These neurons occur in the hypothalamus, mostly in the paraventricular and supraoptic nuclei and their axons project to the neural lobe of the pituitary gland. We have found that nitric oxide (NO) controls luteinizing hormone-releasing hormone (LHRH) release from the hypothalamus acting as a signal transducer in norepinephrine (NE)-induced LHRH release. LHRH not only releases LH from the pituitary but also induces sexual behavior.On the other hand, it is known that oxytocin also stimulates mating behavior and there is some evidence that oxytocin can increase NE release. Therefore, it occurred to us that oxytocin may also stimulate LHRH releave via NE and NO. To test this hypothesis, we incubated medial basal hypothalamic (MBH) explants from adult male rats in vitro. Following a preincubation period of 30 min, MBH fragments were incubated in Krebs-Ringer bicarbonate buffer in the presence of various concentrations of oxytocin. Oxytocin relesed LHRH at concentrations ranging from 0.1 nM to 1muM with a maximal stimulatory effect (P<0.001) at 0.1 muM, but with no stimulatory effect at 10 muM. That these effects were mediated by NO was shown by the fact that incubation of the tissues with NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, blocked the stimulatory effects. Furthermore, the release of LHRH by oxytocin was also blocked by prazocin, an alpha1-adrenergic receptor antagonist, indicating that NE mediated this effect. Oxytocin at the same concentrations also increased the activity of NOS (P<0.01) as measured by the conversion of [14C]arginine to citrulline, which is produced in equimolar amounts with NO by the action of NOS. The release of LHRH induced by oxytocin was also accompanied by a significant (P<0.02) increase in the release of prostaglandin E2 (PGE2), a mediator of LHRH release that is released by NO. On the other hand, incubation of neural lobes with vaious concentrations of sodium nitroprusside (NP) (300 or 600 muM), a releaser of NO, revealed that NO acts to suppres (P<0.01) the release of oxytoxin. Therefore, our results indicate that oxytocin releases LHRH by stimulating NOS via NE, resulting in an increased release of NO, which increases PGE2 release that in turn induces LHRH release. Furthermore, the released NO can act back on oxytocinergic terminals to suppress the release of oxytocin in an ultrashort-loop negative feedback.

Amenorrea hipotalámica, concepto, clasificación y alternativas terapeúticas / Hipothalamic amenorrhea, concept, clasification and therapeutical alternatives

El desarrollo de amenorrea hipotalámica refleja generalmente una respuesta individual al stress ambiental y al propio estilo de vida. En la mayoría de los casos, no hay una anormalidad anatómica detestable del eje hipotálamo-hipófisis-ovario-endometrio. Numerosas evidencias sugieren que el defecto de base es una reducción de la actividad del generador hipotalámico de pulsos de GNRH. Los factores neuroendocrinos que regulan la función de este centro son parcialmente conocidos. El sistema opioidérgico y dopaminérgico han sido implicados como posibles factores en la reducción de la secreción pulsátil de GNRH. Debido a la naturaleza por lo general funcional del trastorno, se espera una reactivación de la actividad pulsátil de GNRH una vez superado los factores que lo desencadenaron. La persistencia de la anovulación obliga a una terapia de reemplazo hormonal fundamentalmente por el riesgo de terapia de reemplazo hormonal fundamentalmente por el riesgo de osteoporosis. En las pacientes que desean fertilidad, la inducción de ovulación con GNRH pulsátil es la alternativa terapéutica más efectiva

Effect of equine hypothalamic extract on hormone secretion by the adenohypophysis of rats

The effect of Equine Hypothalamic Extract (EHE) on pituitary weight and secretion of TSH, FSH-LH and ACTH was studied in the rat. The pituitary respponse to EHE was assessed by measuring (131) I uptake by the thyroid and by weight changes of the pituituray glands, thyroids, adrenals, ovaries and uteri. (131) I uptake of the thyroid and weights of the pituitary, thyroid, adrenal and uterus increased in the treated rats, whereas ovarian weights were similar to control groups. These findings indicate that the EHE containes hypophysiotropic peptides which can stimulate the secretion of pituitary hormones in the rat.

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropinthytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testiculat axis.

Comparison of the effect of hypothalamic neuropeptides upon luteinizing hormone secretion by cultured rat anterior pituitary cells

Bovine median eminence contains a factor difference from gonadotropin-releasing hormone (GnRH) than increases basal luteinizing hormone (LH) secretion and potentiates GnRH-stimulated LH release. We compared the effect of hypothalamic neuropeptides on basal and GnRH-stimulated LH secretion using rat pituitary cells under static incubation conditions to determine if any of them mimics the LH-releasing activity no attributable to GnRH present in bovine median eminence extracts. Both, galanin and eurotensin (10(-9)-10(-5)) stimulated basal LH secretion in a dose-response manner. Galaninincreased 3-4 fold and neurotensin doubled the basal LH secretion. The GnRH antagonist Nal-Glu 10(-6) M abolished the effect of 10(-7) M GnRH and 10(-5)M neurotensin, but did not block the LH-releasing activity of galanin. Leucin-enkephalin, beta-endorphin, substance P and neuropeptide Y (NPY) did not alter basal LH secretion. Neuropeptides produced three types of response on GnRH-stimulated LH release. First...

The influence of the blockade of alfa-melanotroprin (alfa-MSH) on the time of vaginal opening and on LH-RH release

Se obtuvo un anticuerpo específico contra alfa-MSH, conjugado el péptido con albúmina por medio del reactivo de carbodiimida. En este trabajo se establecen los efectos del bloqueo de alfa-MSH por su antisuero específico, en dos modelos fisiológicos: 1) bloqueio del pico sérico de alfa-MSH que se produce en el día 30 en ratas prepúberes y estaría relacionado con la apertura vaginal (AV). 2) el efecto del bloqueo in vitro de alfa-MSH (en eminencia media (EM) de animales en la mañana del proestro) sobre la liberación de LH-RH. La administración del antisuero a través de infusión cocntinua a ratas, desde el día 28 PN al 32 PN retrasa el tiempo de apertura vaginal. El bloqueo de alfa-MSH in vitro a nivel del sistema nervioso central, induce un incremento dosis-dependiente en la liberación de LH-RH al medio de incubación. Estos datos sugerirían que alfa-MSH podría actuar a través de dos vías en los mecanismos regulatorios de la reproducción, uno a nivel periférico y otro, central. En ratas hembras prepúberes, el pico sérico de alfa-MSH que ocurre el día 30, podria participar en la activación de la cadena de eventos, que culminan en la pubertad (nivel periférico). Alfa-MSH a nivel del sistema nervioso central en la rata hembra adulta, ejercería un efecto inhibidor directamente o como modulador de las terminales de EM, influenciando la liberacción de LH-RH (nivel central)

Serotonin stimulates gonadotrophin release by acting directly on the median eminence

Utilizando un sistema de perifusión consistente en dos camaritas en serie se evaluó el efecto de la 5-HT sobre la secreción de gonadotrofinas y PRL. Dos tipos de experimentos fueron realizados: a) se colocaron cinco eminencias medias (EM) en la primera camarita y una anterohipófisis (AH) en la segunda; b) sólo una AH fue colocada en la segunda camarita. Todos los tejidos se disecaron en fresco y fueron obtenidos de ratas hembras sacrificadas entre las 12.00 h y 13.00 h del día del proestro. El agregado de 5-HT (concentraciones finales de 6.0; 0.6 y 0.06 uM) estimuló la secreción de LH y de FSH cuando fue realizada sobre las EM. Este efecto fue anulado por la presencia en el medio perifusión de un bloqueante de receptores serotoninérgicos (ciproheptadina, 1 uM). Inyectada en la conexión entre las EM y la AH, la 5-HT no afectó la secreción de FSH y LH al medio de incubación. En ausencia de las eminencias medias (consición experimental b), la 5-HT tampoco modificó la liberación hipofisaria de gonadotrofinass. En ninguna de las situaciones experimentales estudiadas la 5-HT afectó la liberación de PRL. Nuestros estudios demuestran que la serotonina estimula la liberación de gonadotrofinass actuando sobre receptores serotoninérgicos a nivel de la eminencia media

Regulación neuroendocrina de la reproducción / Neuroendocrine regulation of reproduction

Para que se instale la capacidad reproductiva, el sistema de hipotálamo, hipófisis y gónadas debe haber alcanzado un estado de interdependencia hormonal sincrónico y preciso. El proceso parece iniciarse desde la vida fetal, y se completa en la etapa peripuberal. La secreción pulsátil de LHRH es crucial para el control neuroendocrino del fenómeno reproductivo, ya que su ausencia se puede manifestar como incapacidad para alcanzar la pubertad en ambos sexos, esterilidad y amenorrea. El conocimiento derivado del estudio del proceso fisiológico de la reproducción ha generado progresos importantes en el diagnóstico de enfermedades y nuevas armas terapéuticas de utilidad demostrada en algunos casos y de gran esperanza en otros