Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts

J Endocrinol. 1998 Sep;158(3):401-7. doi: 10.1677/joe.0.1580401.

Abstract

In fibroblasts derived from human adipose tissue, aromatase induction is observed after exposure to 1 microM cortisol in the presence of serum or platelet-derived growth factor (PDGF). Progesterone suppresses this induction in a dose-dependent manner, 10 microM resulting in complete inhibition. A reduced cortisol concentration (0.1 microM) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / enzymology*
  • Analysis of Variance
  • Aromatase / analysis
  • Aromatase / biosynthesis*
  • Aromatase / genetics
  • Becaplermin
  • Bucladesine / pharmacology
  • Cells, Cultured
  • Depression, Chemical
  • Enzyme Induction / drug effects
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Humans
  • Hydrocortisone / pharmacology*
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Placenta / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Polymerase Chain Reaction
  • Progesterone / pharmacology*
  • Proto-Oncogene Proteins c-sis
  • Receptors, Glucocorticoid / metabolism
  • Recombinant Proteins / pharmacology
  • Statistics, Nonparametric

Substances

  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Receptors, Glucocorticoid
  • Recombinant Proteins
  • Becaplermin
  • Progesterone
  • Bucladesine
  • Aromatase
  • Hydrocortisone