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Effect of Estradiol on DHEAS Production in the Human Adrenocortical Cell Line, H295R

Jonathon Oh, MD

William E. Rainey, PhD

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Bruce R. Carr, MD

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9032

Objective: To determine if estradiol regulates DHEA and DHEAS production in a human adrenocortical (H295R) cell line and to determine if this effect is receptor mediated.

Methods: NCI-H295 (H295R) cells were rinsed and placed in phenol red free Dulbecco's Modified Eagle's-F12 medium supplemented with 0.1% charcoal-stripped serum. After 24 hours, cells were rinsed and treated based on experimental design. The effects of estradiol were investigated by: 1) treatment of cells with increasing concentrations of estradiol (300-3000 nmol/L) with or without forskolin (10 µmol/L), 2) treatment of cells with the nonsteroidal synthetic estrogen diethylstilbestrol (DES) (300-3000 nmol/L) with or without forskolin (10 µmol/L), and 3) treatment of cells with an estradiol antagonist (ICI 182,780) in the presence of estradiol.

Results: stradiol alone increased the basal production DHEAS in H295R cells in a concentration-dependent manner with a maximal effect at 1000 nmol/L. Forskolin treatment increased the basal production of DHEAS ten-fold. Estradiol also increased the forskolin stimulation of DHEAS production two-fold. In contrast, DES alone or DES in addition to forskolin did not stimulate DHEAS production. Estradiol, in contrast, inhibited H295R adrenal cell production of cortisol whereas DES exhibited a similar inhibition. The estrogen receptor antagonist ICI 182,780 was unable to inhibit the stimulatory effect of estradiol. Finally, estradiol in a concentration-dependent manner suppressed 3ß-hydroxysteroid dehydrogenase (3ßHSD) activity in H295R adrenal cells.

Conclusion: These experiments support the role of estradiol in regulating DHEAS production by inhibiting 3ßHSD activity; however, the mechanism appears to require high concentrations of estradiol and appears to be independent of the estrogen receptor.

Key Words: Estradiol • DHEAS • adrenal • steroidogenesis

Journal of the Society for Gynecologic Investigation, Vol. 5, No. 3, 144-148 (1998)
DOI: 10.1177/107155769800500307


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