S. Saito et al., EFFECT OF GNRH ANTAGONISTS ON PHORBOL ESTER-INDUCED LH-RELEASE FROM RAT PITUITARY GONADOTROPHS, Endocrine journal, 41(4), 1994, pp. 415-419
We previously reported that a blockade of GnRH receptor activation inh
ibited the already-initiated C-kinase pathway(s). We tried to investig
ate whether this finding is a general phenomenon or not. In this study
, we employed three GnRH antagonists, [D-Phe(2), Pro(3), D-Phe(6)]-GnR
H, [Ac-D-Nal-Ala(2), D-pCl-Phe(2), D-Ser(Rha)(6)]-GnRH, and [Ac-D-p-Cl
-Phe(1,2), D-Trp(3), D-Lys(6), D-Ala(10)]-GnRH (referred to as #1-, #2
-, #3-GnRH antag., respectively). Each antagonist was examined for its
potency against GnRH by analyzing its inhibitory effect on LH release
from pituitary gonadotrophs as well as on the increase in the cytosol
ic Ca2+ concentration. As a result, the #1-GnRH antag. was found to be
weaker than the other two compounds. Consistent with a previous study
, the #3-GnRH antag. inhibited the action of TPA on LH release. Howeve
r, independently of their potency as GnRH-antagonists, the two other a
ntagonists had no inhibitory effect on TPA-induced LH release. While i
t is generally accepted that the C kinase pathway plays a major role i
n the GnRH-induced LH release, not all GnRH antagonists can inhibit LH
release by blocking the already-activated C kinase system.