In vitro LH release and cAMP accumulation induced by synthetic GnRH derivatives.
The LH-releasing activity of GnRH and nine synthetic GnRH derivatives was tested in pituitary monolayer cell culture prepared from female rats. D-amino acid-substituted analogs were found to be 12 to 18-fold as active as GnRH, while D-amino acid GnRH-[1-9]-ethylamide analogs showed 15 to 38-fold activity as compared to GnRH. Dehydroproline-GnRH was equipotent with the parent compound. Asp(A)6-GnRH-EA was less active than GnRH and it was a partial agonist only. All peptides stimulated intracellular cAMP content of the cultured cells at 1 hr and 4 hr of incubation. A nearly uniform 1.8 to 2-fold increase above basal cAMP could be observed with all peptides tested at their maximally active concentrations. However, no correlation could be established between the relative LH-releasing activities and cAMP-elevating potencies of the peptides. The findings suggest that cAMP may not be involved in overall LH-release by GnRH but leave the possibility open that cAMP could be involved in certain steps of mobilizing compartmentalized LH pools of pituitary gonadotrophs.
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D000242:Cyclic AMP