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Endocrinology ; 160(5): 1323-1332, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901026

RESUMO

Hyperprolactinemia causes infertility, but the specific mechanism is unknown. It is clear that elevated prolactin levels suppress pulsatile release of GnRH from the hypothalamus, with a consequent reduction in pulsatile LH secretion from the pituitary. Only a few GnRH neurons express prolactin receptors (Prlrs), however, and thus prolactin must act indirectly in the underlying neural circuitry. Here, we have tested the hypothesis that prolactin-induced inhibition of LH secretion is mediated by kisspeptin neurons, which provide major excitatory inputs to GnRH neurons. To evaluate pulsatile LH secretion, we collected serial blood samples from diestrous mice and measured LH levels by ultrasensitive ELISA. Acute prolactin administration decreased LH pulses in wild-type mice. Kisspeptin neurons in the arcuate nucleus and in the rostral periventricular area of the third ventricle (RP3V) acutely responded to prolactin, but prolactin-induced signaling in kisspeptin neurons was up to fourfold higher in the arcuate nucleus when compared with the RP3V. Consistent with this, conditional knockout of Prlr specifically in arcuate nucleus kisspeptin neurons prevented prolactin-induced suppression of LH secretion. Our data establish that during hyperprolactinemia, suppression of pulsatile LH secretion is mediated by Prlr on arcuate kisspeptin neurons.


Assuntos
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Kisspeptinas/metabolismo , Hormônio Luteinizante/metabolismo , Neurônios/efeitos dos fármacos , Prolactina/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/citologia , Núcleo Arqueado do Hipotálamo/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hiperprolactinemia/genética , Hiperprolactinemia/metabolismo , Injeções Subcutâneas , Hormônio Luteinizante/sangue , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/fisiologia , Prolactina/administração & dosagem , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo
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