Biology of Reproduction, Vol 23, 595-605, Copyright © 1980 by Society for the Study of Reproduction

Hormonal Control of Pyridine Nucleotide Activity in the Uterus: A Model for Progestational Differentiation

¹ Department of Physiology and Cell Biology, University of Kansas, Lawrence, Kansas 66045

To evaluate the roles of estrogen and progesterone in regulating NADP content in endometrium during progestation, adult rats were ovaniectomized on Day 0 of pseudopregnancy. Using a radiometric enzymatic recycling assay, daily measurements of NADP⁺ and NADPH were made in five experiments: 1) ovariectomized controls; replacement with 2) 1.0 µg estrone/day, or 3) 2.0 mg progesterone/day; 4) a combination of 1.0 µg estrone + 2.0 mg progesterone (Exp. A); and 5) 0.5 µg estrone + 1.0 mg progesterone on Day 0 followed by the regimen of Exp. A thereafter (Exp. B). Following ovariectomy, the content of NADP declined, but the concentration stabilized at a level equivalent to that measured during proestrus (18-21 pmoles/mg). Daily treatment with estrogen generated a bimodal pattern with peaks on Days 2 and 5 (30-32 pmoles/mg), whereas treatment with progesterone induced peaks on Days 3 and 6 (40-67 pmoles/mg). A significant increase in the NADP⁺/NADPH ratio, measured on Day 1 in ovariectomized rats, was blocked by estrogen until Day 3, but was not affected by progesterone. Addition of estrogen to the progesterone regimen (Exp. A) stimulated an increase in tissue mass without a concomitant increase in progesteronemaintained NADP content and without altering the progesterone-maintained pattern. However, slight alterations in the steroid hormone regimen on Day 0 (Exp. B) significantly altered the subsequent patterns of NADP content and concentration on Days 3-4 to mimic the transient peak in activity measured at this time in intact pseudopregnant rats. The data indicate that at the dosages of hormones used (limited by physiological constraints), the production of high concentrations of NADP during early progestation is a progestogen-dependent phenomenon, modulated by estrogen. A relationship of these hormone-dependent changes to key facets of progestational differentiation dependent on pyridine nucleotide metabolism is presented.

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ACKNOWLEDGMENTS This investigation was supported in part by grants from the University of Kansas General Research Fund and Biomedical Research Fund, and by NIH Grant HD 11797.