Regulation of angiotensin II receptors in cultured rat ovarian granulosa cells by follicle-stimulating hormone and angiotensin II.
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.
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Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio 44195-5069.
Bumpus
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Husain
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D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D000001:Calcimycin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D001141:Aromatase; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate