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Neuroendocrinology. 2017;105(1):77-89. doi: 10.1159/000448520. Epub 2016 Jul 25.

Estradiol Upregulates Kisspeptin Expression in the Preoptic Area of both the Male and Female Rhesus Monkey (Macaca mulatta): Implications for the Hypothalamic Control of Ovulation in Highly Evolved Primates.

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Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA.


The aim of this immunohistochemical study was to evaluate the distribution of kisspeptin neurons in the preoptic area (POA) of gonadally intact adult male and female rhesus monkeys, and to determine whether imposition of an estradiol (E2)-positive feedback signal in the castrate male increased kisspeptin in the POA. Additionally, kisspeptin in the POA of the intact female was examined during an LH surge induced prematurely by E2 administered in the early follicular phase. The number of kisspeptin neurons in the POA of males and females was similar. Immunoactive kisspeptin perikarya were not observed in the POA of castrate adult males, but such neurons in these animals were present within 12 h of imposing an increment in circulating E2 concentrations that in a screening study conducted 4-6 weeks earlier had elicited an LH surge. As expected, premature induction of an LH surge by E2 early in the follicular phase was associated with upregulation of kisspeptin in the POA. These results represent the first description of immunoreactive kisspeptin cell bodies in the POA of the macaque brain and provide further support for the view that (1) kisspeptin neurons in the POA of the female monkey are a target for the positive feedback action of E2 and (2) the hypothalamic mechanism which mediates this action of E2 in primates is not subjected to perinatal programming by testicular testosterone. Moreover, our findings indicate that maintenance of the kisspeptin content in the POA of intact male monkeys requires the action of E2, presumably generated by aromatization of testicular testosterone at the hypothalamic level.


Kisspeptin; Luteinizing hormone surge; Preoptic area; Sexual dimorphism

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