A potent LH-RH antagonist (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH
(Antag) was used to study the differential regulation of FSH and LH se
cretion by endogenous LH-RH in ovariectomized (OVX) and regularly cycl
ing rats. The endogenous LH-RH was suppressed by single injections of
Antag in OVX animals and by long-term treatment with Antag in normal a
nd OVX rats. Serum and pituitary LH and FSH, as well as serum estradio
l (E2) and progesterone (P) was determined by RIA during and/or after
the treatment. The direct effect of the antagonistic analog on the ova
rian P release was tested in vitro using the isolated luteal cell syst
em. Single injections of the Antag in OVX animals caused prompt and ma
rked suppression of the serum LH (-80%), while no decrease of the seru
m FSH. Long-term treatment with the same analog decreased the serum LH
by 50% but did not modify the serum FSH. In normal rats, serum LH dro
pped to undetectable levels, while serum FSH did not change significan
tly. Long-term treatment with the antagonist also resulted in divergen
t alterations in the pituitary gonadotropin concentrations. In OVX ani
mals, the pituitary LH content moderately elevated (+21%), however, th
e FSH did not change. In normal rats, ovarian cycles were interrupted,
and no ovulation appeared during the treatment. The pituitary LH conc
entration increased by 46%, while the FSH decreased by 43%. Marked dep
ression was found in the serum P (-60%) but no significant change in t
he serum E2 levels. Incubation of isolated luteal cells with the Antag
did not influence the HCG-induced P secretion in vitro, demonstrating
that the in vivo inhibitory effect of the antagonistic LH-RH analog o
n the P secretion asserts not directly on the ovarian LH-RH receptors,
but through inhibition of the endogenous LH-RH. Our studies give evid
ence that the long-term treatment with LH-RH antagonist suppress the L
H and P but not the FSH and E2 secretion, and provide new data suggest
ing the presence of a FSH-releasing factor in the CNS.