Progesterone inhibits glucocorticoiddependent aromatase induction in human adipose fibroblasts

In fibroblasts derived from human adipose tissue, aro-matase induction is observed after exposure to 1 µM cortisol in the presence of serum or platelet-derived growth factor (PDGF). Progesterone suppresses this induc-tion in a dose-dependent manner, 10 µM resulting in complete inhibition. A reduced cortisol concentration (0·1 µM) concomitantly reduces the progesterone concen-tration required for eVective inhibition (10–100 nM). This eVect of progesterone is specific, as neither the release of cellular enzymes nor aromatase induction by dibutyryl-cAMP, which acts independently from cortisol, are aVected. However, the inhibitory eVect 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 eVect 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 con-sidered 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