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.
Highlights
Following our original studies on hCG/LH receptors, GTP-binding stimulatory (Gs) proteins and adenyl cyclase enzyme characterization in human endometrium [1,2], a number of clinical and molecular biology studies have increasingly been published on this topic
It is well known that the actions of hCG and LH are initiated by a specific binding to the membrane-bound hCG/LH receptors, followed by coupling of the receptors to GTP-binding stimulatory (Gsα) protein and activation of the adenylyl cyclase (AC), the transmembrane effector enzyme responsible for the intracellular synthesis of cyclic AMP [14]
Immunoblot analysis demonstrated the presence of hCG/ LH receptors and the GTP-binding stimulatory (Gs) protein in the endometrial membranes obtained from both hormone replacement cycles and stimulated cycles
Summary
Following our original studies on hCG/LH receptors, G proteins and adenyl cyclase enzyme characterization in human endometrium [1,2], a number of clinical and molecular biology studies have increasingly been published on this topic. In the uterus the presence of hCG/LH receptors has been shown in all parts including myometrium, large, small blood vessels and endometrium During pregnancy they are active and favour vasodilatation and uterine tone relaxation by coupling to probably different signal transduction pathways associated with prostaglandins and cAMP production, respectively [15,16]. Available information basically relies on in vitro studies of human endometrial cells or in vivo studies on the baboon uterus [17,18,19,20] This notwithstanding, all the investigators agree that whenever the endometrium is exposed to hCG a consistent and constant activation of the COX2 enzyme is derived along with an increased eicosanoids biosynthesis [17,21,22,23]. These data allow a reasonable interpretation of the premature stromal maturation of endometrium apparently associated with reduced implantation rates during cycles of controlled ovarian stimulation when an exogenous injection of hCG is administered
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
