Aging Attenuates the Pituitary Response to Gonadotropin-Releasing Hormone

Abstract

Complex changes in GnRH secretion occur with aging in women, but little is known about the effect of aging on the pituitary per se. The aim of the study was to determine whether pituitary responsiveness to GnRH is attenuated with aging. A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness in Clinical Research Center studies at an academic medical center. Subjects were healthy postmenopausal women (PMW) aged 48-57 yr (n = 10) or 70-77 yr (n= 9). A suppressive dose of the NAL-GLU GnRH antagonist (150 microg/kg sc) was administered and was followed by GnRH doses of 25, 75, 250, or 750 ng/kg iv every 4 h. The LH response to GnRH was attenuated with aging (P = 0.05) with an interaction between age and dose (P = 0.01) such that the LH amplitude was less in older PMW at the higher doses (250 ng/kg, 50 +/- 9 vs. 29 +/- 4.9 IU/liter, for young and old PMW, respectively, P = 0.02; and 750 ng/kg, 97.7 +/- 11 vs. 70.2 +/- 9.3 IU/liter, P = 0.002), but not the lower doses of GnRH. The FSH response to GnRH was also attenuated with aging in PMW (P = 0.005). In studies that isolated the pituitary from endogenous GnRH stimulation, aging attenuated the LH and FSH responses to exogenous GnRH in PMW. These studies indicate that the pituitary plays a role in the decline in gonadotropin levels with aging, further supporting the potential contribution of age-associated changes in both hypothalamic and pituitary function to reproductive senescence.