Adrenal Luteinizing Hormone Receptors: A Potential Mechanism for the Perimenopausal Rise of Adrenal Androgens

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 515-547-Female Reproductive Endocrinology
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-521
Bill L Lasley*1, Ch V Rao2, Min Lu2, Alan James Conley1, Dallas M Hyde1, Frank F Ventimiglia1, Nancy A Gee1, Don R Canfield1, Daniel S McConnell3, Antoni J Duleba4, Frank Z Stanczyk5 and John H Morrison6
1University of California, Davis, CA, 2Florida International University, Miami, FL, 3University of Michigan, Ann Arbor, MI, 4University of California, San Diego, La Jolla, CA, 5University of Southern California, Keck School of Medicine, Los Angeles, CA, 6Icahn School of Medicine at Mount Sinai, New York, NY
Background:  The human adrenal cortex (AC) of most mid-aged women increases production of delta-5 steroids during the menopausal transition (MT) within the time period that circulating gonadotropin levels are rising and relatively normal ovarian cycles continue.  However, the mechanism(s) for this gender- and ovarian stage-specific event is not known.  Using the nonhuman primate, we have shown that older female macaques respond to human chorionic gonadotropin (hCG) by producing increased dehydroepiandrosterone sulfate (DHEAS). These findings suggest that changes in gonadotropin levels may act to modulate both the structure and function of the higher primate adrenal cortex.

Objective:To investigate the mechanism(s) responsible for the change in AC structure and function of higher primate females.

Hypothesis:Regulation of gonadotropins following ovariectomy (OVX) by different patterns of ovarian steroid leads to specifically different changes in the structure and function of the AC.

Experimental Design: Intact control and long-term OVX female nonhuman primates (n=24) were either intact and untreated (n=6) or OVX and treated with vehicle (n=6), estrogen alone (E2, n=6) or estrogen plus progesterone (E2+P, n=6) for 7 to 12 months. Animals ranged in age from 7-25 years. The adrenal glands from all animals were then evaluated for structural and functional changes.

Results:The structure and function of the AC were modulated differently by endogenous sex steroids and hormone replacement therapy (HT) regimens. Preliminary immunohistochemical staining of fixed sections revealed the presence of luteinizing hormone receptors (LHR) in all three AC layers, with staining differences reflecting age, ovarian status and HT.

Summary:These data provide direct evidence that the structure and function of the AC of higher primate females can be modulated by changes in ovarian status via steroid hormone secretion patterns.  These results also demonstrate that HT regimens can simulate the action of the ovary on the AC during the MT and may be responsible for the changes that are observed in the secretion of adrenal steroids in most mid-aged women.

Conclusion:  These findings suggest that elevated circulating luteinizing hormone (LH) levels through activation of their receptors in AC contribute to adrenal steroid secretion during MT. The response of the AC to different patterns of ovarian steroid levels associated with different regimens of HT provides a plausible mechanism to explain the rise in adrenal steroid production during and following the MT for most women.

Nothing to Disclose: BLL, CVR, ML, AJC, DMH, FFV, NAG, DRC, DSM, AJD, FZS, JHM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Funded in part by NIH P51 RR00169 (California National Primate Research Center Base Grant) and NIA P01 AG01675 (JHM).