TITLE:
Failure of hCG/LH receptors to stimulate the transmembrane effector adenylyl cyclase in human endometrium
AUTHORS:
L. Bernardini, I. Moretti-Rojas, M. Brush, F. J. Rojas, J. P. Balmaceda
KEYWORDS:
hCG/LH Receptors; Human Endometrium; Membrane Signal Transduction; Adenylyl Cyclase
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.10,
October
18,
2013
ABSTRACT: The functional significance of the endometrial hCG/ LH
receptors has been related to a rapid release of prostaglandins. However, as
compared to gonads and myometrium, in-endometrium mechanisms of transmembrane
signalling of the hCG/LH receptors are probably not conventional and remain
unclear. Here we investigated, in vivo, the potential of hCG to interact
with, and stimulate the membrane effector enzyme, adenylyl cyclase (AC), in
human endometrium. Hormonal and nonhormonal activation of AC was tested in
membrane fractions prepared from endometrial biopsies obtained from patients
undergoing evaluation cycles for
hormone replacement therapy (HRT) and controlled ovarian hyperstimulation
(COH). AC activity was determined by the direct conversion of the
substrate ATP into cAMP under unstimulated conditions and in the presence of
the non-hormonal activators guanyl nucleotide and forskolin. Also AC activity
was tested in the presence of hCG under conditions allowing maximal enzyme
stimulation. Isoproterenol and prostaglandin E2 (PGE2) were included for
comparison. Immunoblot analyses demonstrated the presence of hCG/LH receptors
and Gsα protein and other members of
the G protein family in the membrane fractions. Endometrial membranes also
exhibited high levels of AC activity compared to luteal membranes used as
control. Stimulation by GMP-P(NH)P alone was 196 ± 63 (n = 8) (pmol/mg/ min ± SD). Neither hCG nor isoproterenol showed stimulation
of endometrial AC (210 ± 65, and 197 ± 53, respectively; n = 66 assays). But PGE2 stimulated
the enzyme system significantly (264 ± 63, p tions from human endometrium
express all the AC system components, namely, hCG/LH receptors, Gsα protein and AC; however, hCG does not
stimulate the endometrial AC system. Our data
indicate that, in great contrast to gonadal
receptors, endometrial hCG/ LH receptors are not coupled to the transmembrane
AC effector. The well known release of eicosanoids in response to hCG suggests
that these receptors are functional in human endometrium but throughout a
signalling system different from AC. This enzyme is certainly coupled to and
directly activated by eicosanoids and other embryonic signals.