Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta)

Abstract

Reproductive function in all vertebrates is controlled by the circhoral release of the neuropeptide, GnRH, into the portal capillary system leading to the anterior pituitary. Despite its primary role in sexual maturation and the maintenance of adult reproductive function, changes in the concentrations and pattern of GnRH release have not yet been reported in any primate species during the menopausal transition and postmenopause. Such knowledge is essential for ascertaining both the mechanisms for, and consequences of, the menopausal process. Here we used a push-pull perfusion method to measure and compare the parameters of pulsatile GnRH release in adult rhesus monkeys at 8.4 +/- 1.5 yr (young adult females, early follicular phase, n = 6) and 28.8 +/- 0.3 yr (aged females, n = 4, of which two monkeys were in the menopausal transition, and two were postmenopausal). Our results demonstrate that: 1) GnRH release is pulsatile in both young and aged monkeys; 2) mean concentrations of GnRH increase during reproductive aging; and 3) GnRH pulse frequency does not differ between aged monkeys and young monkeys in the early follicular phase. We conclude that not only do GnRH neurons have the continued capacity to release GnRH in a pulsatile manner but also they can do so with enhanced GnRH levels in aged primates. To our knowledge, this is the first direct demonstration of elevated pulsatile GnRH concentrations in a primate species during reproductive senescence, a result that may have implications for menopausal symptoms.