Characterization of kisspeptin neurons in the human rostral hypothalamus.
2020
INTRODUCTION: Kisspeptin (KP) neurons in the rostral periventricular area (RP3V) of female rodents mediate positive estrogen feedback to gonadotropin-releasing hormone neurons and thus, play fundamental role in the mid-cycle luteinizing hormone (LH) surge. The RP3V is sexually dimorphic and male rodents with lower KP cell numbers are unable to mount estrogen-induced LH surges. OBJECTIVE: To find and characterize the homologous KP neurons in the human brain, we studied formalin-fixed post mortem hypothalami. METHODS: Immunohistochemical techniques were used. RESULTS: Distribution of KP neurons in the rostral hypothalamus overlapped with different subdivision of the paraventricular nucleus. Cell numbers decreased after menopause, indicating that estrogens positively regulate KP gene expression in the rostral hypothalamus in humans, similarly to several other species. Young adult women and men had similar cell numbers, as opposed to rodents having more KP neurons in the RP3V of females. Human KP neurons differed neurochemically as well from the homologous rodent cells in that they were devoid of enkephalins, galanin and tyrosine hydroxylase. Further, they did not contain known KP neuron markers of the human infundibular nucleus, neurokinin B, Substance P and cocaine- and amphetamine-regulated transcript but received afferent input from these KP neurons. CONCLUSIONS: Identification and positive estrogenic regulation of KP neurons in the human rostral hypothalamus challenge the long-held view that positive estrogen feedback may be restricted to the mediobasal part of the hypothalamus in primates and point to the need of further anatomical, molecular and functional studies of rostral hypothalamic KP neurons.
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