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Regulation of Aromatase mRNA and Estradiol Biosynthesis in Rat Ovarian Granulosa and Luteal Cells by Prolactin

Department of Cell Biology, Baylor College of Medicine Houston, Texas 77030
Department of Obstetrics and Gynecology, Baylor College of Medicine Houston, Texas 77030

Address requests for reprints to: J. S. Richards, Ph.D., Department of Cell Biology, One Baylor Plaza, Houston, Texas 77030.

Abstract

Regulation by PRL of aromatase (P450arom) mRNA and protein and estradiol (E) biosynthesis was examined in granulosa cells during early stages of luteinization in vitro and in vivo. PRL caused a dosedependent (10–1000 ng/ml) decrease in P450arom mRNA and E biosynthesis (>99%) in luteinized rat granulosa cells in vitro, even when the cells were cultured in the presence of insulin and hydrocortisone (hormones known to synergize with PRL to induce proteins in mammary tissue) or in the presence of forskolin (a nonhormonal stimulator of cAMP). PRL also prevented the marked increases in aromatase mRNA and E biosynthesis stimulated by FSH and forskolin in nonluteinized preovulatory granulosa cells in culture. These effects of PRL on granulosa cells in culture were specific for aromatase and were not observed for other proteins, such as cholesterol side-chain cleavage cytochrome P450 (P450scc) and ₂-macroglobulin. PRL also decreased P450arom mRNA and protein during the early stages of luteinization in vivo. PRL administered to rats beginning day 1 postovulation to mimic hormone release during pseudopregnancy reduced the progressive increase in P450arom mRNA occurring in corpora lutea on days 3–4 in ovulated rats not treated with PRL. CB 154, a dopamine agonist that inhibits pituitary release of PRL, caused P450arom mRNA and protein to decrease 50% if given to pregnant rats on days 8–10 of gestation, but increased P450arom mRNA and protein if given to pregnant rats on days 10–12 of gestation. These diverse effects of PRL in pregnancy suggest that placental factors may modify the response of luteal cells to PRL during gestation. Taken together, the results of these studies provide the first unequivocal evidence that pituitary PRL can act to inhibit aromatase mRNA and E biosynthesis in granulosa cells of rat preovulatory follicles before and during the early stages of luteinization. Our results demonstrate that the effects of PRL on aromatase in vivo are diverse and are dependent on the endocrine status of the rat. The specific cellular and molecular mechanisms involved in mediating the diverse effects of PRL on aromatase in rat ovarian tissues remain to be determined.

FOOTNOTES

This work was supported by NIH Grants HD-16229 and HD-16272 (to J.S.R.), the American Cancer Society (BC-627; to J.S.R.), and the Women's Fund (to J.S.K.).

Received for publication September 18, 1989. Revision received October 18, 1989. Accepted for publication October 23, 1989.

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