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Sci Rep ; 14(1): 10190, 2024 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702366

RESUMEN

Dysfunction of central serotonergic neurons is known to cause depressive disorders in humans, who often show reproductive and/or glucose metabolism disorders. This study examined whether dorsal raphe (DR) serotonergic neurons sense high glucose availability to upregulate reproductive function via activating hypothalamic arcuate (ARC) kisspeptin neurons (= KNDy neurons), a dominant stimulator of gonadotropin-releasing hormone (GnRH)/gonadotropin pulses, using female rats and goats. RNA-seq and histological analysis revealed that stimulatory serotonin-2C receptor (5HT2CR) was mainly expressed in the KNDy neurons in female rats. The serotonergic reuptake inhibitor administration into the mediobasal hypothalamus (MBH), including the ARC, significantly blocked glucoprivic suppression of luteinizing hormone (LH) pulses and hyperglycemia induced by intravenous 2-deoxy-D-glucose (2DG) administration in female rats. A local infusion of glucose into the DR significantly increased in vivo serotonin release in the MBH and partly restored LH pulses and hyperglycemia in the 2DG-treated female rats. Furthermore, central administration of serotonin or a 5HT2CR agonist immediately evoked GnRH pulse generator activity, and central 5HT2CR antagonism blocked the serotonin-induced facilitation of GnRH pulse generator activity in ovariectomized goats. These results suggest that DR serotonergic neurons sense high glucose availability to reduce gluconeogenesis and upregulate reproductive function by activating GnRH/LH pulse generator activity in mammals.


Asunto(s)
Glucosa , Cabras , Hormona Liberadora de Gonadotropina , Hormona Luteinizante , Receptor de Serotonina 5-HT2C , Neuronas Serotoninérgicas , Animales , Hormona Luteinizante/metabolismo , Femenino , Receptor de Serotonina 5-HT2C/metabolismo , Ratas , Neuronas Serotoninérgicas/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Glucosa/metabolismo , Serotonina/metabolismo , Kisspeptinas/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Dorsal del Rafe/metabolismo , Núcleo Dorsal del Rafe/efectos de los fármacos , Ratas Sprague-Dawley
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