Expression of LH receptor in nonpregnant mouse endometrium: LH induction of 3β-HSD and de novo synthesis of progesterone

Abstract

In mouse uterus, at the late diestrus stage LH binding sites have previously been described. The aim of our study was to confirm the existence of LH receptor (Lhr (Lhcgr)) mRNA and its protein in mouse endometrium. Endometrium at all stages of the estrous cycle contained Lhr mRNA, essentially identical to that found in mouse ovary. Endometrium also contained a 72 kDa immunoreactive receptor protein that bound to mouse anti-LHR antibody in western blot. Both receptor mRNA and protein were maximally expressed in the endometrium at metestrus and LH caused a significant increase in their expression levels. Endometrium also contained 3b-hydroxy steroid dehydrogenase (3b-hsd) mRNA and 3b-HSD protein. LH addition elevated their expression and activity as evident from increased conversion of labeled pregnenolone to progesterone (P 4 ) and de novo P 4 synthesis. LH-induced endometrial P 4 synthesis is mediated through expression of steroidogenic acute regulatory (Star) gene. Results demonstrated that LH-induced P 4 synthesis in endometrium is possibly mediated through the cAMP pathway. Involvement of a MAPK pathway was also evident. Gonadotropin-stimulated endometrial P 4 synthesis was markedly attenuated by an antagonist of MEK1/2, PD98059. LH-stimulated MEK1/2-dependent phosphorylation of ERK1/2 in a concentration-and time-dependant manner in cultured endometrial tissues. Moreover, involvement of cAMP in LH-stimulated activation of ERK1/2 was also evident. It is therefore possible that the major signaling pathways regulating endometrial steroidogenesis in mouse, including the adenylate cyclase and MAP kinase pathways, converge at a point distal to activation of protein kinase A and ERK1/2.

Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation

“…Exogenous addition of androgens to human decidualized stromal cells appeared to protect the cells from oxidative stress (38), suggesting that local increases in bioavailable androgens within the tissue that are not detected by measuring circulating concentrations of steroids also play a role in protecting the tissue at the onset of menses in women. Although the enzymes necessary for intrauterine biosynthesis of androgens are also present in the mouse uterus (39, 40), mice do not synthesize adrenal androgens that form the key precursor pool in women. Thus, in the current study, we used an exogenous dose of DHT to explore whether an AR agonist that cannot be metabolized to estrogens could have an impact on endometrial tissue breakdown in a well‐defined model.…”

Superovulation with human chorionic gonadotropin (hCG) trigger and gonadotropin releasing hormone agonist (GnRHa) trigger differentially alter essential angiogenic factors in the endometrium in a mouse ART model†

“…However, there is little data on the effects of the GnRH agonist on endometrial receptivity and placentation. GnRH and LH receptors have been reported in human and rodent endometrium [18]. Several clinical studies have suggested decreased pregnancy rates related to inadequate luteal support following GnRH agonist trigger [19].…”

Influence of VEGFR and LHCGR on endometrial adenocarcinoma

“…In addition, ER and LHCGR were demonstrated to contribute to testicular germ cell cancer development and to the formation of remote metastasis of these tumors (37). The observed association between LHCGR and PR may be explained by the induction of progesterone synthesis by LHCGR (38). A previous study added RU486, a progesterone antagonist, to luteinized human mural granulosa cells, and demonstrated inhibition of proliferation, progesterone secretion and LHCGR as a result (39).…”