Adrenal Function in Healthy Aging

Principal Investigator: Professor Bill Lasley, PhD

Funding for the project: National Institute of Health, P01

In mid-aged women the longitudinal profile of circulating dehydroepiandrosterone sulfate (DHEAS) concentrations during the menopausal transition exhibits an inflection and rise prior to the cessation of ovarian cycles. A similar change in DHEAS is observed in the aged female laboratory macaque. Neither the source of nor mechanism for this rise in DHEAS has been established. To investigate this phenomenon nonhuman primate females were screened for ovarian function then treated with a gonadotropin releasing hormone agonist (GnRHa) to suppress circulating bioactive luteinizing hormone (LH) and a single dose challenge of hCG was then administered 14 days post GnRHa treatment in order to determine if LH/CG could accelerate circulating weak androgen production. Serum androgens, bioactive LH and urinary metabolites of ovarian sex steroids were monitored before, during and following these treatments. Circulating LH bioactivity and immunoreactive DHEAS concentrations were suppressed in all animals in 14 days post GnRHa administration. Serum LH/CG bioactivity increased following hCG challenge and serum bioactivity exhibited a transient rise and subsequent suppression. Circulating DHEAS levels were significantly increased at 3 hours post hCG administration and the increase in DHEAS in individual animals was proportional to the pre-treatment baseline. These data show that circulating DHEAS concentrations can be increased by hCG challenge in the aged female non-human animal model while no change was observed in ovarian sex steroid excretion.