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Regulation of Progesterone Formation by Human Placental Cells in Culture^*

Departments of Obstetrics and Gynecology University of Maryland School of Medicine Baltimore, Maryland 21201;
Anatomy University of Maryland School of Medicine Baltimore, Maryland 21201;
the Department of Physiology, Eastern Virginia Medical School Norfolk, Virginia 23501

Address all correspondence and requests for reprints to: Eugene D.Albrecht, Ph.D., Department of Obstetrics and Gynecology, Universityof Maryland School of Medicine, Bressler Research Laboratories 11-015, 655 West Baltimore Street, Baltimore, Maryland 21201.

Abstract

In the present study, a culture system of human placental cells was established to examine the role of estrogen and androgen in progesterone (P₄) formation. Normal human placentae were obtained at term, and cells were dispersed in Hank's Balanced Salt Solution (5 ml/g tissue) containing 0.1% collagenase, 0.1% hyaluronidase, 0.01% deoxyribonuclease, and 1% fetal bovine serum for 2 h at 37 C. Dispersed placental cells (10⁸ cells/ml) were placed in medium 199 with modified Earle's salts (pH 7.4) containing 10% fetal bovine serum, 12.5 mM HEPES buffer, 26 mM NaHCO₃, and 40 µg/ml Gentamycin-SO4 and incubated for 72 h at 37 C and 5% CO₂ in air to allow cell attachment. Medium was then changed (time zero), and P₄ formation was studied thereafter.

Culture of placental cells for 96 h resulted in linear increases in P₄ and estradiol (E₂) formation, indicating the maintenance of cell viability and steroidogenic function. Mean ± SE P₄ formation at 48 h was 246 ± 16 pg/µg DNA. To assess the role of estrogen on P₄ formation, placental cells were incubated for a period of 48 h with various amounts (10^-7-10^-4 M) of the antiestrogen ethamoxytriphetol (MER-25), the aromatase inhibitor 4- hydroxyandrostenedione (4-OHA), and/or E₂. Both MER-25 and 4-OHA resulted in a dose-dependent decline (P < 0.01) in P₄ formation (80% decline at 10^-4 M MER-25 or 4-OHA). The marked reduction in P₄ formation caused by 4-OHA alone was reversed by concomitant addition of E₂ however, E₂ alone had no effect. To assess the role of androgens on P4 formation, cells were incubated for 48 h with increasing amounts (10^-7-10^-4 M) of androstenedione, dehydroepiandrosterone (DHA), or dihydrotestosterone. Although the formation of E₂ was enhanced by DHA, formation of P₄ was not affected by the aromatizable androgens DHA or androstenedione or the nonaromatizable dihydrotestosterone.

The decline in P₄ formation by human placental cells in culture elicited by MER-25 or 4-OHA supports the hypothesis of a regulatory role for estrogen in placental P₄ formation during human pregnancy. The lack of effect of exogenous estrogen suggests that the action of estrogen on P₄ formation may be permissive. (Endocrinology 119: 998-1003, 1986)

Footnotes

^* This work was supported by NIH Research Grant HD-13294.

Received December 21, 1985.

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