Objective: We propose that the adrenal gland of an older higher primate female animal model will respond to human chorionic gonadotropin (hCG) hormone challenge by secreting additional dehydroepiandrosterone sulfate (DHEAS). Such a response in surgically and chemically castrated animals will provide proof of concept and a validated animal model for future studies to explore the rise in DHEAS during the menopausal transition of women.
Methods: Twenty-four 18- to 26-year-old female cynomolgus monkeys were screened for ovarian function and then either ovariectomized (n = 4) or treated with a gonadotropin-releasing hormone agonist (GnRHa; n = 20) to block ovarian steroid production. After a recovery period from surgical procedure or down-regulation, a single-dose challenge (1,000 IU/animal, IM) of hCG was then administered to determine if luteinizing hormone (LH)/chorionic gonadotropin could accelerate circulating DHEAS production. Serum DHEAS, bioactive LH, and urinary metabolites of ovarian sex steroids were monitored before, during, and after these treatments.
Results: Circulating LH bioactivity and immunoreactive DHEAS concentrations were suppressed in all animals 14 days postadministration of GnRHa. Urinary metabolites of estradiol and progesterone remained low after the surgical procedure or a flare reaction to GnRHa. Circulating DHEAS levels were increased after hCG administration, and the increase in individual animals was proportional to the pretreatment DHEAS at baseline. Circulating DHEAS concentrations were positively correlated to endogenous LH bioactive concentrations prior to hCG challenge and were subsequently further elevated by the hCG challenge while no concomitant change in ovarian steroid hormone excretion was observed.
Conclusions: These data demonstrate a positive adrenal androgen response to LH/chorionic gonadotropin in older female higher primates and suggest a mechanism for the rise in adrenal androgen production during the menopausal transition in women. These results also illustrate that the nonhuman primate animal model can be effectively used to investigate this phenomenon.
From the 1Center for Health and the Environment, University of California, Davis, CA; 2Department of Public Health, University of Tennessee, Knoxville, TN; and 3California National Primate Research Center, University of California, Davis, CA.
Received May 21, 2012; revised and accepted July 12, 2012.
Francisco M. Moran and Jiangang Chen contributed equally to this work.
Funding/support: This work was supported by the National Institutes of Health/National Center for Research Resources (P51-RR000169; California National Primate Research Center), National Institute of Environmental Health Sciences Superfund Research Program (P42 ES04699), National Institute of Environmental Health Sciences (P01 ES06198 and P30 ES005707), and National Institute on Aging (AG02224 and AG17164).
Financial disclosure/conflicts of interest: None reported.
Address correspondence to: Bill L. Lasley, PhD, Center for Health and the Environment, University of California, One Shields Avenue, Davis, CA 95616. E-mail: email@example.com