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.