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.To find and characterize the homologous KP neurons in the
human brain, we studied formalin-fixed post mortem hypothalami.Immunohistochemical
techniques were used.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.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.
