GnRH agonist-induced inhibitory and stimulatory effects during ovarian follicular maturation.
The in vivo regulation of ovarian gonadotropin and prolactin receptors and adenylate cyclase activity by FSH, and the potent GnRH agonist [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), was studied in immature hypophysectomized diethylstilbestrol-implanted rats. During FSH treatment over a 48 h period, FSH receptors increased 2-fold with the maximum response during the first 12 h, whereas LH and prolactin receptors increased by 10-fold and 6-fold with the maximum response from 12 to 48 h. Administration of GnRHa at any time during the 48 h period of FSH treatment inhibited the subsequent development of gonadotropin and PRL receptors. In contrast, administration of a single dose of 10 micrograms GnRHa after 48 h of FSH treatment stimulated follicular luteinization and caused increases in basal adenylate cyclase activity, ovarian weight and PRL receptor content, and concomitant decreases in gonadotropin receptors and adenylate cyclase responses. In the immature follicles of animals not primed with FSH, GnRHa caused progressive inhibition of FSH-sensitive adenylate cyclase activity, with a decrease in FSH receptors, but increased both basal and GMP-P(NH)P-stimulated adenylate cyclase activities. These results demonstrate that GnRHa causes marked inhibition of gonadotropin receptor expression in the basal and FSH-stimulated ovary. This decrease in gonadotropin receptors is an important component of the mechanism by which GnRH agonists inhibit ovarian gonadotropin-sensitive adenylate cyclase activity. In addition, these peptides exert stimulatory effects upon ovarian weight and basal adenylate cyclase activity, and cause an increase in PRL receptors and luteinization of mature ovarian follicles.(ABSTRACT TRUNCATED AT 250 WORDS)
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D011962:Receptors, FSH; D011974:Receptors, LH; D011981:Receptors, Prolactin
D011956:Receptors, Cell Surface; D011962:Receptors, FSH; D011974:Receptors, LH; D011981:Receptors, Prolactin; D007987:Gonadotropin-Releasing Hormone; C010661:surfagon; D005640:Follicle Stimulating Hormone; D000262:Adenylyl Cyclases