Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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Biology of Reproduction, Vol 21, 1025-1033, Copyright © 1979 by Society for the Study of Reproduction

Alterations of Progesterone Metabolism in Immature Rat Ovaries by Luteinizing Hormone

DAVID T. ARMSTRONG 1

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


Metabolism of progesterone in ovaries of prepubertal rats has been investigated by incubating intact ovaries from immature rats in Krebs-Ringer bicarbonate buffer containing 10-6 M progesterone-4-[14C] and isolating the radioactive metabolites formed after varying periods of incubation. Androsterone was the most abundant metabolite produced by ovaries from 28-30-day-old rats. Luteinizing hormone (LH) injected 0.5-4 h before autopsy, or added directly to incubation media, resulted in markedly decreased formation of androsterone with a concomitant proportional increase in production of 3agr-OH-5agr-pregnane-20-one (3agr-OH-5agr-P). Production of other androgens (androstenedione, testosterone, 5agr-androstane-3agr,17beta-diol), which accumulated in smaller amounts than androsterone, was also inhibited by LH. Prolactin administration for 6 days before autopsy resulted in only minor alterations of progesterone metabolism, causing small increases in accumulation of 5agr-pregnane-3,20-dione (5agr-P) and 3agr-OH-5agr-P in the absence of LH and slightly enhancing the inhibitory effects of LH on formation of androstenedione and androsterone.

Ovaries from 23-day-old rats produced significantly more androsterone and less androstenedione than did those from 29-day-old rats in the absence of exogenous hormone treatment.

When follicular growth was induced and first estrus synchronized by administration of 4 IU pregnant mare serum gonadotropin (PMSG) to 28-day-old rats at 0800 h (Day 0), androsterone production from progesterone-4-[14C] gradually increased, reaching maximum levels at 2200 h on Day 1 and remained elevated until 1400 h on Day 2 (the equivalent of proestrus). With the first detectable rise in serum LH levels on Day 2, androsterone production declined abruptly, reaching minimum levels at 2200 h on Day 2. Production of 3agr-OH-5agr-P, a relatively minor metabolite before the LH surge, increased markedly and became the major metabolite at 1800 and 2200 h, coincident with the LH surge.

These results are consistent with a regulatory role for 5agr-reduced gonadal steroids in the ovarian maturation processes during the peripubertal period and indicate an ability of LH, both exogenous and endogenous, to alter markedly the ratio of C19/C21, steroids by an inhibitory action on the 17agr-hydroxylase-C17,20-lyase step.

Note:
ACKNOWLEDGMENTS I wish to thank Ms. Margarethe Van Eck and Mr. Michael Kraemer for highly skilled technical assistance, Dr. R. F. Weick for performing the LH assays, the Hormone Distribution Program, NIH, U.S.A. and Ayerst Pharmaceutical Laboratories, Montreal, Canada, for generous donations of hormones used in these studies.

Submitted on March 2, 1979
Accepted on June 19, 1979






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