GONADOTROPIN RECEPTORS OF THE PRIMATE CORPUS LUTEUM

The proposed research is designed to test further the hypothesis that
modulation of the gonadotropin receptor-adenylyl cyclase system is an
important mechanism regulating corpus luteum function in primates during
the menstrual cycle and early pregnancy. Based on progress in this
laboratory, specific aims are presented: (a) to determine whether
bona-fide receptors for luteinizing hormone (LH) and chorionic gonadotropin
(CG) are masked in luteal membranes and to identify conditions which
mask/unmask receptors, (b) to correlate the number of available, occupied,
and masked LH-CG receptors with the functional state of the corpus luteum
during the menstrual cycle, (c) to investigate in vitro the direct effects
of potential luteolytic agents on the gonadotropin receptor-adenylyl
cyclase system, (d) to compare the effect of in vivo exposure to hCG
(designed to mimic early pregnancy levels) on gonadotropin
receptor-adenylyl cyclase activity in young vs. mature corpora lutea, and
(e) to develop an in vivo model examining the ability of intraovarian
estrogen and prostaglandin to modulate gonadotropin receptor-adenylyl
cyclase activity and the function of the primate corpus luteum. The adult,
female rhesus monkey continues as the animal choice for our studies on the
primate corpus luteum, with comparative studies employing luteal tissue
from the pseudopregnant rat and the pig. Available and masked receptors
will be characterized via specific 125I-labeled hLH/hCG binding to macaque
luteal preparations before and after exposure to unmasking agents (e.g.,
ethanol). Adenylyl cyclase activity will be assessed from the conversion
of [Alpha32P] ATP to [Alpha32P] cyclic AMP by luteal preparations. These
studies will provide new information on the cellular mechanims regulating
the corpus luteum during the menstrual cycle and early pregnancy, with
application to the control of human fertility and infertility. In
particular, the investigation will determine whether heterologous and
homologous regulation of the gonadotropin receptor-adenylyl cyclase system,
by potent luteolytic agents and gonadotropins, respectively, plays an
important role in the regulation of the function/lifespan of the primate
corpus luteum.