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Endocrinology, doi:10.1210/endo-109-4-1303
Endocrinology Vol. 109, No. 4 1303-1305
Copyright © 1981 by the Endocrine Society.
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EVIDENCE THAT GRANULOSA CELL AROMATASE INDUCTION/ACTIVATION BY FOLLICLE-STIMULATING HORMONE IS AN ANDROGEN RECEPTOR-REGULATED PROCESS IN-VITRO

STEPHEN G. HILLIER and FRANS A. DE ZWART

Department of Obstetrics & Gynecology, Leiden University Medical Centre, 2333 AA Leiden, The Netherlands

Abstract

The role of androgen in aromatase induction/activation by follicle-stimulating hormone (FSH) was studied in cultured granulosa cells from estrogen-pretreated, immature rat ovaries. Aromatase activity was measured in washed cell monolayers after a 48-h culture in medium containing hFSH and/or various sex steroids or their analogues. Culture with hFSH (100 ng/ml) plus 10-7 M testosterone (T) stimulated aromatase activity to a level similar to that of granulosa cells from preovulatory follicles in the cyclic adult on the morning of proestrus. But if T was omitted, or replaced by estrogen (DES) or progesterone (P), the response to hFSH was at least 90% lower. The abilities of T, androstenedione, five nonaromatizable 5{alpha}-reduced androgens, an aromatase reaction intermediate (19-hydroxyandrostenedione), and a pharmacological competitive aromatase inhibitor ({delta}1testololactone) to stimulate the aromatase response to hFSH were proportionate to their stimulatory effects on P production during the culture. By both criteria T was the most potent androgen while 19-hydroxyandrostenedione and {delta}1-testololactone were completely inactive. The stimulatory effect of 10-7 M T on the aromatase response to hFSH was inhibited by the nonsteroidal antiandrogen SCH 16423 (ID50 = 3.6 x 10-6 M). These results indicate that granulosa cell aromatase induction/activation by hFSH is an androgen receptor-regulated process in vitro.




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