Multiple inhibitory effects of a luteinizing hormone-releasing hormone agonist on hCG-dependent steroidogenesis and on FSH-dependent responses in ovarian cells in vivo and in vitro.
[125I] labelled [D-Leu6, des-Gly-NH10(2)] LH-RH ethylamide (LH-RHa), when injected into immature female rats, bound specifically not only to the pituitary but also to the ovaries. LH-RHa inhibited hCG-stimulated progesterone production and ovarian weight augmentation in hypophysectomized immature female rats in vivo. FSH-induced ovarian hCG receptors and ovarian weight gain in diethylstilbestrol (DES)-treated hypophysectomized immature female rats were also suppressed by LH-RHa. Progesterone production by rat luteal cells in vitro was inhibited by LH-RHa. LH-RHa did not change the affinity or population of LH/hCG receptor in porcine granulosa cells in short term incubation. However, LH-RHa inhibited induction of LH/hCG receptor stimulated by FSH and insulin in long term culture of porcine granulosa cells. LH-RHa delayed hCG-stimulated cyclic AMP accumulation in porcine granulosa cells. These findings suggest that LH-RHa inhibits hCG-stimulated cyclic AMP accumulation and subsequent progesterone production as well as FSH-stimulated LH/hCG receptor induction by acting directly on ovarian cells.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003338:Corpus Luteum / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007016:Hypophysectomy; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D016729:Leuprolide; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D013552:Swine
D006063:Chorionic Gonadotropin; D007328:Insulin; D011956:Receptors, Cell Surface; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D016729:Leuprolide