AJP - Endocrinology and Metabolism, Vol 246, Issue 1 44-E51, Copyright © 1984 by American Physiological Society
LH release is facilitated by agents that alter cyclic AMP-generating system
M. J. Cronin, W. S. Evans, E. L. Hewlett and M. O. Thorner
The issue of whether the adenosine 3',5'-monophosphate (cAMP)-generating
system contributes to luteinizing hormone (LH) release was addressed by
using several complementary probes in vitro. Pertussis toxin is considered
to modify covalently an inhibitory adenylate cyclase regulatory protein.
Treatment of gonadotrophs with this toxin increased both basal LH release
and the efficacy of gonadotropin-releasing hormone (GnRH)-stimulated LH
release with no apparent effect on GnRH potency. Cholera toxin, which
probably activates adenylate cyclase by covalently altering another
regulatory protein, forskolin, which directly stimulates the catalytic
subunit of adenylate cyclase, and the cAMP analogue 8-Br-cAMP amplified
both basal LH release (in a dose-dependent manner) and GnRH-stimulated LH
release after a lag of 1 (cholera toxin and 8-Br-cAmP) and 4 (forskolin) h.
It is noteworthy that these belated effects occurred in spite of the fact
that cellular cAMP accumulation was markedly increased within 30 min after
cholera toxin and at 1 min after forskolin addition. There was no change in
total radioimmunoassayable LH (cellular + released) in either the basal or
GnRH-treated cells after cholera toxin and forskolin for up to 24 h.
Finally, the forskolin-amplified LH release was reversible and calcium
dependent because D-600, EDTA, and calcium-free medium inhibited this
effect. These results, generated with three complementary probes that
affect integral proteins of the adenylate cyclase complex, suggest a
function for cAMP in modulating LH release.
