CI628 inhibits follicle-stimulating hormone (FSH)-induced increases in FSH receptors of the rat ovary: requirement of estradiol for FSH action.
Although estradiol (E2) alone does not increase receptors for FSH in granulosa cells, E2 priming before administration of FSH increases numbers of FSH receptors significantly compared with FSH alone. We hypothesized that if E2 is required for FSH to increase its own receptor, blocking estrogen action should prevent FSH-induced increases in FSH receptors. Five groups of hypophysectomized rats were injected sc with: saline at 0 h; the antiestrogen CI628 (1 mg) at -6 h; human FSH (hFSH, 2 micrograms) at 0 h; CI628 at -6 h, then hFSH at 0 h; and CI628 plus E2 (2 mg) at -6 h, then FSH at 0 h. Animals were decapitated at 0, 6, 12, or 24 h, and granulosa membrane receptors for FSH, LH, and nuclear receptors for E2 were measured. LH receptor levels increased only after administration of E2 before hFSH. Treatment with hFSH for 6 h increased numbers of FSH receptors 3-fold (P less than 0.01) without any increase in numbers of E2 receptors. At 12 and 24 h, hFSH increased numbers of FSH and E2 receptors 6- and 7-fold (P less than 0.01) over controls. CI628 prevented the hFSH-induced increases in FSH receptors at 6, 12, and 24 h. Administration of E2 concomitant with CI628 before hFSH significantly reversed the inhibitory effects of CI628 on hFSH-induced increases in FSH receptors. There were no changes in affinity of FSH or E2 receptors from 0 to 24 h. To determine whether E2 was acting on the adenylate cyclase system, the ability of hFSH to increase the content of cAMP in granulosa cells in each treatment group was determined. After an iv injection of hFSH, cAMP levels were similar in CI628- and saline-treated rats but had increased 6-fold (P less than 0.01) in hFSH or CI628 plus hFSH-treated animals. Thus, blocking hFSH-induced increases in FSH and E2 receptor appeared to have no effect on FSH stimulation of cAMP. In conclusion E2 appears to be required for FSH action, perhaps by acting within granulosa cells distal to the cAMP-adenylate cyclase system.
Tonetta
S A
SA
Spicer
L J
LJ
Ireland
J J
JJ
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors*; D007016:Hypophysectomy; D009594:Nitromifene / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D011759:Pyrrolidines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000378:metabolism; D011962:Receptors, FSH; D011974:Receptors, LH; D013739:Testosterone / Q000097:blood
D011759:Pyrrolidines; D011956:Receptors, Cell Surface; D011959:Receptors, Estradiol; D011962:Receptors, FSH; D011974:Receptors, LH; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D009594:Nitromifene; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP