Antigonadotropic actions of GnRH agonist on ovarian cells in vivo and in vitro.
GnRH and its agonists have recently been shown to inhibit a variety of reproductive functions, in addition to its well-known gonadotropin releasing action in the pituitary. In order to determine the inhibitory mechanism and the site of action of these peptides in ovary, the direct actions of an agonistic analogue [D-Leu6, des-Gly-NH2] GnRH ethylamide on hypophysectomized immature rat ovaries in vivo and on rat luteal cells as well as porcine granulosa cells incubated in vitro were investigated. 125I-Labeled GnRH agonist, when injected to immature female rats, bound specifically not only to pituitary but also to ovaries. GnRH agonist inhibited hCG stimulation of progesterone production and ovarian weight augmentation in hypophysectomized immature female rats in vivo. FSH-stimulated induction of ovarian LH/hCG receptors and ovarian weight gain in diethylstilbestrol (DES)-treated hypophysectomized immature female rats were also suppressed by GnRH agonist. Moreover, treatment with GnRH agonist inhibited hCG-stimulated progesterone production by rat luteal cells incubated in vitro. In short time incubation of porcine granulosa cells obtained from medium follicles, the capacity and affinity of LH/hCG receptors were not affected by GnRH agonist. However, in long term culture of porcine granulosa cells obtained from small follicles, concomitant treatment with GnRH agonist markedly inhibited the induction of LH/hCG receptors stimulated by FSH and insulin. It may be possible that GnRH agonist prevents the differentiation of granulosa cells and subsequent acquisition of LH/hCG receptors, but has no effect on the LH/hCG receptors already induced. On the other hand, GnRH agonist delayed hCG-stimulated accumulation of cyclic AMP in porcine granulosa cells obtained from medium follicles. This delay of cyclic AMP accumulation may be responsible for the inhibition of progesterone production by ovarian cells. These findings suggest that GnRH agonist acts directly on ovarian cells and inhibits the action of FSH and LH/hCG, independently.
D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology; D016729:Leuprolide; D008858:Microscopy, Phase-Contrast; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011974:Receptors, LH; D013552:Swine
D007328:Insulin; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D016729:Leuprolide