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Biology of Reproduction, Vol 21, 1035-1042, Copyright © 1979 by Society for the Study of Reproduction

A Mechanism for the Intraovarian Inhibitory Action of Estrogen on Androgen Production

PETER C. K. LEUNG 1, and DAVID T. ARMSTRONG 1

1 Department of Physiology and Department of Obstetrics and Gynaecology, University of Western Ontario, London, Ontario, Canada N6A 5A5


Immature female rats were sacrificed at 0, 4, 8 or 16 h following a single s.c. injection of estradiol-17beta (estradiol, 1 mg). Ovaries from each animal were incubated individually: one in the presence of LH (10 µg/ml) for 4 h, the other with progesterone-4-[14C] (10-6 M) for 2 h. For the LH incubated ovaries, in vivo treatment with estradiol had no significant effect on progesterone accumulation, whereas production of both testosterone and androstenedione was inhibited by estradiol in a manner dependent on the duration of estradiol treatment in vivo. Analysis of the conversion of radioactive progesterone to its major metabolites by the contralateral ovaries revealed a time-dependent inhibition by estradiol in the formation of androstenedione, 5agr-androstanedione and androsterone, whereas the production of 5agr-pregnanedione and 3agr-OH-5agr-pregnan-20-one was significantly stimulated, also in a time-dependent manner. In another experiment, in vivo stimulation for 1 h with LH produced alterations in the pattern of metabolites of progesterone-4-[14C] identical to those found upon treatment with estradiol; both treatments resulted in a marked stimulation of 3agr-OH-5agr-pregnan-20-one, accompanied by an inhibition, of similar magnitude, of production of androsterone. These results suggest that 1) estradiol may act to inhibit ovarian androgen production by impairing the C17agr-hydroxylase/C17,20-lyase enzyme systems, thereby diverting C21-substrates through alternate metabolic pathways leading to accumulation of 5agr-pregnane compounds and 2) the inhibitory action of LH upon ovarian androgen production may be mediated by estrogen.

Note:
ACKNOWLEDGMENTS We thank the Hormone Distribution Office, NIH, Bethesda, MD, for donating the luteinizing hormone (NIH-LH-B8), Dr. D. K. Pomerantz for determination of the serum levels of LH and FSH, Dr. J. Zamecnik and Mr. G. Barbe for the preparation of the antibody and validation of the radioimmunoassay for androstenedione and Dr. T. G. Kennedy for advice with statistical analysis.

Submitted on March 21, 1979
Accepted on June 19, 1979




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Copyright © 1979 by the Society for the Study of Reproduction.