Gonadotropin-releasing hormone stimulation of pituitary gonadotrope cells produces an increase in intracellular calcium.
Gonadotropin-releasing hormone (GnRH) stimulates pituitary gonadotrope cells to release luteinizing hormone (LH). Previous studies have indicated a role for Ca+2 in this process; however, the present study provides the first measurements of an increased intracellular Ca+2 concentration. Pituitary cell cultures enriched for gonadotropes were loaded with quin 2, a fluorescent Ca+2-sensitive molecule. Subsequent addition of GnRH to these cells produced a rapid (within 10 sec) increase in fluorescence (indicating an increase in intracellular free Ca+2). In contrast, two GnRH analogs, des1 GnRH (a very low-affinity binder to the GnRH receptor) and Ac[D-pCl-Phe1,2] DTrp3 DLys6 DAla10-GnRH (a pure GnRH antagonist) produced no such Ca+2 change, thus showing a correlation between increased intracellular Ca+2 and LH release. A functional relationship between increased Ca+2 and LH release was suggested by experiments in which LH release was inhibited from cells loaded with high levels of intracellular quin 2 (in order to chelate intracellular Ca+2). Since this inhibition was completely reversed by addition of the Ca+2 ionophore A23187, quin 2 was not toxic at the concentrations used and apparently inhibited LH release by buffering intracellular Ca+2. The results presented here are consistent with the hypothesis that GnRH-stimulated LH release is mediated by increased intracellular Ca+2 and support the notion that the rate-limiting step in GnRH-stimulated LH release is distal to Ca+2 mobilization.
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D005260:Female; D005455:Fluorescent Antibody Technique; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D000634:Aminoquinolines; D007987:Gonadotropin-Releasing Hormone; D000001:Calcimycin; C045215:LHRH (2-10); C041811:LHRH, N-Ac-Trp(1)-(4-Cl-Phe)(2)-Trp(3)-Arg(6)-Ala(10)-; D007986:Luteinizing Hormone; C035739:Quin2; D002118:Calcium