O. Lesouhaitier et al., EFFECT OF THE TRIAKONTATETRANEUROPEPTIDE (TTN) ON CORTICOSTEROID SECRETION BY THE FROG ADRENAL-GLAND, Journal of molecular endocrinology, 20(1), 1998, pp. 45-53
Diazepam-binding inhibitor (DBI) was initially isolated from the rat b
rain as a result of its ability to compete with benzodiazepines for th
eir receptors. Immunohistochemical studies have recently shown the pre
sence of peripheral-type benzodiazepine receptor (PBR)- and DBI-like i
mmunoreactivity in the frog adrenal gland. The aim of the present stud
y was to investigate the effect of two biologically active DBI-derived
peptides, the triakonta-tetraneuropeptide [TTN; DBI(17-50)] and the o
ctadecaneuropeptide [ODN; DBI(33-50)], on corticosteroid secretion by
frog adrenocortical cells. Exposure of frog adrenal explants to graded
concentrations of TTN (3.16 x 10(-8) to 3.16 x 10(-6) M) induced a do
se-related increase in corticosterone and aldosterone secretion. In co
ntrast, ODN did not modify corticosteroid output. When repeated pulses
of TTN (10(-6) M) were administered at 2-h intervals, the response of
the adrenal explants to the second dose of TTN was markedly reduced,
suggesting the existence of a desensitization phenomenon. Exposure of
dispersed adrenal cells to TTN also induced a marked stimulation of co
rticosteroid secretion, indicating that TTN acts directly on adrenocor
tical cells. The central-type benzodiazepine receptor (CBR) agonist, c
lonazepam, did not stimulate corticosteroid secretion and the CBR anta
gonist, flumazenil, did not block the stimulatory action of TTN. Simil
arly, the PBR agonist, Ro5-4864, did not mimic the stimulatory effect
of TTN and the PBR antagonist, flunitrazepam, did not affect the stimu
latory action of TTN. The present study provides the first evidence fo
r a stimulatory effect of TTN on intact adrenocortical cells. The rece
ptor mediating the corticotropic action of TTN is not related to centr
al- or peripheral-type benzodiazepine receptors. Our data suggest that
TTN, released by chromaffin cells, may act as a paracrine factor regu
lating the activity of adrenocortical cells.