Biology of Reproduction, Vol 15, 107-114, Copyright © 1976 by Society for the Study of Reproduction

Uterotrophic Effects of Testosterone and 5-Dihydrotestosterone in Intact and Ovariectomized Immature Female Rats

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

The relative effectiveness of exogenous testosterone and 5-dihydrotestosterone (DHT) in causing uterine growth in intact vs ovariectomized immature rats has been investigated to determine the extent to which the uterotrophic responses to these androgens depends upon their aromatization in the ovaries. Ovariectomy depressed the ability of testosterone to a much greater extent than that of DHT to induce uterine growth, especially hypertrophy of the uterine luminal epithelial cells. This ability was not further decreased by adrenalectomy. Exogenous estradiol-17 administration was as effective in stimulating uterine growth and increased luminal epithelial cell height in ovariectomized rats treated with DHT as in those treated with testosterone, indicating that the decreased effectiveness of DHT to induce these changes was not the result of greater anti-estrogenic activity of DHT than of testosterone. Ovarian contents of immunoreactive estradiol-17 increased markedly, and approximately in parallel with increased ovarian contents of immunoreactive testosterone + DHT 6 and 12 h after s.c. injection of testosterone; by 24 h, ovarian contents of both steroids declined approximately to pre-injection levels. In contrast, s.c. injection of DHT was followed by significantly decreased ovarian contents of estradiol-17 at all 3 time intervals. It is concluded that increased ovarian formation of estradiol-17 occurs when ovarian contents of testosterone are elevated by administration of high dosages of exogenous testosterone to immature rats, and that this estrogen contributes significantly to the uterine growth and histologic changes which follow testosterone administration. The lack of such changes as a result of DHT administration attests to the inability of this androgen to undergo aromatization in vivo; the decreased ovarian content of estradiol-17 following DHT administration suggests that this steroid, in addition to being ineffectual as an estrogen precursor, may actually play a role in inhibition of ovarian estrogen biosynthesis.

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ACKNOWLEDGMENTS We are indebted to Joan Calaresu, Ann Robson, and Ram Srivastava for their skilled technical assistance, and to Dr. T. G. Kennedy and G. Wielgosz for advice and assistance with statistical analyses. This research was supported by grants from the Medical Research Council (Canada) and the Ford Foundation.

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