Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells

Fertil Steril. 1991 May;55(5):922-6. doi: 10.1016/s0015-0282(16)54300-3.

Abstract

The authors studied the effects of 4-hydroxyandrostene-3,17-dione (4-OHA) on progesterone (P), 17 beta-estradiol (E2), and 20 alpha-hydroxy-4-pregnen-3-one synthesis and pregnenolone accumulation in cultured human midluteal cells. A dose-dependent inhibition with and without human chorionic gonadotropin (hCG) of E2 and P production was observed. The accumulation of pregnenolone was significantly enhanced three to fourfold by 4-OHA in this culture system, as compared with control value. In addition, a sevenfold increase on pregnenolone accumulation was observed in the presence of 4-OHA plus 10 IU of hCG as compared with control values and 2.2-fold as compared with the 4-OHA treatments. These in vitro findings indicate a direct effect of 4-OHA on luteal steroidogenesis. Nevertheless, the suppressive effect of 4-OHA on P and E2 production is located at different sites of the steroidogenic pathway. In addition, the results demonstrate that hCG in the presence of 4-OHA stimulated pregnenolone accumulation, suggesting that the inhibition of P synthesis is in some steps after the formation of pregnenolone. These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 20-alpha-Dihydroprogesterone / biosynthesis
  • Adult
  • Androstenedione / analogs & derivatives*
  • Androstenedione / pharmacology
  • Aromatase Inhibitors*
  • Cells, Cultured
  • Chorionic Gonadotropin / pharmacology
  • Dose-Response Relationship, Drug
  • Estradiol / biosynthesis
  • Female
  • Humans
  • Luteal Cells / drug effects
  • Luteal Cells / metabolism*
  • Pregnenolone / administration & dosage
  • Pregnenolone / biosynthesis
  • Progesterone / biosynthesis*
  • Testosterone / administration & dosage
  • Testosterone / pharmacology

Substances

  • Aromatase Inhibitors
  • Chorionic Gonadotropin
  • 20-alpha-Dihydroprogesterone
  • Testosterone
  • Androstenedione
  • Progesterone
  • Estradiol
  • Pregnenolone
  • formestane