Regulation of angiotensin II receptors in cultured rat ovarian granulosa cells by follicle-stimulating hormone and angiotensin II

J Biol Chem. 1988 Aug 25;263(24):11954-61.

Abstract

The regulation of ovarian granulosa cell angiotensin II (Ang-II) receptor formation and progesterone secretion by follicle-stimulating hormone (FSH) and Ang-II was studied in cultured cells prepared from hypophysectomized, diethylstilbestrol-treated immature rats. Ang-II receptors (estimated by the specific cell binding of the Ang-II receptor antagonist 125I-[Sar1,Ile8]Ang-II) were present on freshly prepared granulosa cells and increased by over 2-fold (to 2150 binding sites/cell; KD = 0.5 nM) when cultured in serum-free medium for 48 h. FSH prevented the normal increase in Ang-II receptor expression. Maximal FSH-dependent decrease in Ang-II receptors and increase in progesterone secretion occurred at 100 ng/ml FSH. The inhibitory effect of FSH on granulosa cell Ang-II receptor content was partially mimicked by the cAMP analogue 8-bromo-cAMP, since 8-bromo-cAMP suppressed (by 96%) Ang-II receptor content to a greater extent than FSH (by 60%). Granulosa cell Ang-II receptor content was not modified by progesterone or 17 beta-estradiol, but was decreased by testosterone (by 35%). Ang-II also produced a decrease in granulosa cell Ang-II receptor content, but did not modify progesterone secretion or aromatase activity. The effect of Ang-II on granulosa cell Ang-II receptor content was mimicked by the Ca2+ ionophore A23187, but not by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, suggesting that an elevation of cytosolic Ca2+ may be important for the homologous down-regulation of the Ang-II receptor. These data show homologous and heterologous down-regulation of granulosa cell Ang-II receptors. If these regulatory mechanisms exist in the FSH-sensitive healthy follicle, our findings suggest that in the process of maturation, healthy and dominant follicles may become decoupled from angiotensinergic influences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Sarcosine-8-Isoleucine Angiotensin II / metabolism
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology*
  • Animals
  • Aromatase / metabolism
  • Calcimycin / pharmacology
  • Cells, Cultured
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Estradiol / pharmacology
  • Female
  • Follicle Stimulating Hormone / pharmacology*
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism*
  • Kinetics
  • Progesterone / metabolism
  • Progesterone / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Angiotensin / drug effects
  • Receptors, Angiotensin / metabolism*
  • Testosterone / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Receptors, Angiotensin
  • Angiotensin II
  • 8-Bromo Cyclic Adenosine Monophosphate
  • 8-bromocyclic GMP
  • Calcimycin
  • Testosterone
  • Progesterone
  • Estradiol
  • Follicle Stimulating Hormone
  • 1-Sarcosine-8-Isoleucine Angiotensin II
  • Aromatase
  • Cyclic GMP
  • Tetradecanoylphorbol Acetate