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Biology of Reproduction, Vol 24, 445-453, Copyright © 1981 by Society for the Study of Reproduction

5agr-Androstane-3agr, 17beta-Diol: Inhibitor of Sexual Maturation in the Female Rat

ILZE KRAULIS 1, SALLY J. NAISH 1, D. GRAVENOR 1, , and K. B. RUF 1

1 Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal H3A 1A1, Canada


The possible regulatory role of 5agr-androstane-3agr, 17beta-diol (3agr-diol) in the onset of puberty was investigated in sexually immature female rats. Single or repeated administration of 3agr-diol prevented the occurrence of estrogen-progesterone-triggered LH and FSH surges. Similar effects were obtained with the related 5agr-reduced androgen 5agr-androstane-17beta-ol-3-one (dihydrotestosterone) but not with the 3beta-epimer of 3beta-diol. Single acute administration of 3agr-diol also abolished the estrogen-induced increase in pituitary responses to an LHRH analogue. When administered for 3 weeks via Silastic implants, 3agr-diol but not 3agr-diol prevented spontaneous sexual maturation as judged by the absence of vaginal cyclicity, uterine growth, and formation of corpora lutea. Chronic exposure to 3agr-diol led to a drastic increase in the pituitary FSH/LH ratio and to reduced estrogen and progesterone output by the ovary. Three weeks after removal of 3agr-diol implants, five of six females conceived and produced normal litters.

It is concluded that 3agr-diol prevents the triggering of gonadotropin surges by gonadal steroids and the estrogen-induced sensitization of pituitary gonadotrophs to LHRH. Chronic exposure accordingly inhibits the development of ovarian cyclicity. In view of the high blood concentrations found in the prepubertal period and the reversibility of its action, 3agr-diol appears suited for the role of a physiological inhibitor of sexual maturation in the female rat.

Note:
ACKNOWLEDGMENTS We wish to thank Dr. M. van Houten for providing the photomicrographs, Dr. J. R. Challis for the estradiol antiserum, and Mrs. Helli Traikov for expert technical assistance. Steroid radioimmunoassays were performed by Miss Chantal Morin; gonadotropins were determined by Mrs. Linda Carter and Miss Shirley Whyte with material provided by the NIAMDD rat pituitary hormone distribution program and Dr. A. F. Parlow. The study was supported by grant MA-6235 from the Canadian Medical Research Council.

Submitted on June 2, 1980
Accepted on October 31, 1980




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[Abstract] [Full Text]


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