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Biology of Reproduction, Vol 14, 306-313, Copyright © 1976 by Society for the Study of Reproduction

Control of Placental 3 beta-Hydroxy-Dgr5-Steroid Dehydrogenase: Comparison of Enzyme Characteristics in Man, Cow, Goat, Rat and Rhesus Monkey

MARGARET WIENER 1

1 Center for Experimental Pathology and Toxicology, Albany Medical College of Union University, Albany, New York 12208


The inhibition of the conversion of pregnenolone to progesterone by endogenous substances previously observed in rat and human placentas in vitro was investigated in placentas of three additional mammalian species. 20agr-hydroxy-pregn-4-ene-3-one, produced in vivo by reduction of the 20-ketone group of progesterone, inhibited this conversion in placental homogenates from cow, goat and rhesus monkey. The apparent Ki’s ranged from 0.5-3.4 µM. In contrast, in vitro progesterone synthesis in corpora lutea of pregnancy from rabbit, rat, and a 12-week human pregnancy was little affected by 20agr-hydroxy-pregn-4-ene-3-one.

Cortisone also inhibited progesterone synthesis by placental homogenates from man, cow, goat and monkey. Rat placentas were not studied. Measurements on related C-21 steroids revealed considerable structural specificity, with cortisone the most effective inhibitor tested in this group of compounds. Prostaglandins A1, A2, B2, E1, E2 and F2agr had no apparent effect on the reaction.

The progressive increase in specific activity of placental 3beta-hydroxy-Dgr5-steroid dehydrogenase on dilution previously described for man and rat was also apparent in cow, goat, and rhesus monkey, supporting earlier suggestions of the existence of another endogenous inhibitor. Hypotheses are presented that both 20agr-hydroxypregn-4-ene-3-one and the second inhibitory substance are concerned with control and/or maintenance of progesterone levels during pregnancy, while cortisone is involved in reduction of these levels at the time of parturition.

Note:
ACKNOWLEDGMENTS Prostaglandins were the gift of Dr. John Pike of The Upjohn Company. Mrs. Louise B. Kwapinski of Westmere Goat Farm, Albany, New York and Mr. Ralph Miller of Cole Hill Farm, East Berne, New York, donated the goat and cow placentas used in this work. Mrs. Katherine Stowell and Mrs. Judith Levine supplied technical assistance in the performance of the experiments. This work was supported by R01-HD06579 and P01-ES226 from the U.S. Public Health Service.

Submitted on September 4, 1975
Accepted on November 10, 1975






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Copyright © 1976 by the Society for the Study of Reproduction.