Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts

Schmidt, M. and Renner, C. and Loeffler, G. (1998) Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts. JOURNAL OF ENDOCRINOLOGY, 158 (3). pp. 401-407. ISSN 0022-0795, 1479-6805

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Abstract

In fibroblasts derived from human adipose tissue, aromatase induction is observed after exposure to 1 mu M cortisol in the presence of serum or platelet-derived growth factor (PDGF). Progesterone suppresses this induction in a dose-dependent manner, 10 mu M resulting in complete inhibition. A reduced cortisol concentration (0.1 mu M) concomitantly reduces the progesterone concentration required for effective inhibition (10-100 nM). This effect of progesterone is specific, as neither the release of cellular enzymes nor aromatase induction by dibutyryl-cAMP, which acts independently from cortisol, are affected. However, the inhibitory effect of progesterone requires its presence throughout the induction period. Kinetic studies in intact cells reveal a reduced number of aromatase active sites upon progesterone treatment, whereas progesterone at near-physiological concentration (100 nM) does not inhibit aromatase activity in isolated microsomes. Semi-quantitative reverse transcriptase PCR analysis shows reduced amounts of aromatase mRNA in progesterone-treated cells, indicating specific inhibition of the glucocorticoid-dependent pathway of aromatase induction. The inhibitory effect of progesterone is not blocked by the anti-progestin ZK114043, excluding action via progesterone receptors and indicating competition for the glucocorticoid receptor. Progesterone must be considered a potential physiological inhibitor of glucocorticoid-dependent aromatase induction in adipose tissue. It is proposed that it is a suppressor of aromatase induction in adipose tissue in premenopausal women.

Item Type: Article
Uncontrolled Keywords: TISSUE STROMAL CELLS; ESTROGEN BIOSYNTHESIS; PLASMA ANDROSTENEDIONE; HORMONE RECEPTORS; GENE-EXPRESSION; PHORBOL ESTERS; GROWTH-FACTORS; CYTOCHROME-P-450; BREAST; CONVERSION;
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 25 Apr 2023 13:25
Last Modified: 25 Apr 2023 13:25
URI: https://pred.uni-regensburg.de/id/eprint/49563

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