Estradiol alters the effectiveness of gonadotropin-releasing hormone (GnRH) in ovine pituitary cultures: GnRH receptors versus responsiveness to GnRH.
17 beta-Estradiol (E) rapidly (5-12 h) induced ovine pituitary cultures to increase their binding of des-Gly10-[D-Ala6] GnRH ethylamide by 2.5- to 4.5-fold. The ED50 for E was near 0.1 nM. Scatchard analysis indicated that E increased binding by increasing receptors for GnRH. GnRH-stimulated release of LH increased 2-fold along with the increase in GnRH receptors, but heightened responsiveness to GnRH disappeared after 27 h of E treatment even though GnRH receptors remained elevated. These data are consistent with the concepts that 1) E increased GnRH receptors, which initially enhanced gonadotroph responsiveness to GnRH, and 2) E subsequently nullified the increased response to GnRH by blocking a mechanism of LH secretion not associated with GnRH receptor number. Further support for this hypothesis came from studies with porcine follicular inhibin. Inhibin in ovine pituitary culture concomitantly increased GnRH receptors by 5-fold and GnRH-stimulated LH secretion by 2-fold. Inhibin maintained both effects long term (48 h). When E was added along with inhibin, the increase in GnRH receptor number became greater than with either hormone alone (7-fold increase at 48 h), but the initial increase in GnRH-stimulated LH secretion was fully inhibited by E at 48 h. The increase in GnRH receptors caused by E may be important physiologically to help create the preovulatory LH surge; the delayed inhibitory action of E on GnRH-stimulated LH secretion may limit the LH surge.
Laws
S C
SC
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622.
Webster
J C
JC
Miller
W L
WL
D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007265:Inhibins / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011966:Receptors, LHRH / Q000378:metabolism*; D012756:Sheep
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C010661:surfagon; D007265:Inhibins; D007986:Luteinizing Hormone