Induction of G protein-coupled estrogen receptor (GPER) and nuclear steroid hormone receptors by gonadotropins in human granulosa cells.

Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and estrogen receptor ß (ERß) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation. The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH. Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH and LH increased ERß, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERß and PR in luteinized granulosa cells.

Expression of CRH, CRH-related peptide and CRH receptor in the ovary and potential CRH signalling pathways.

Capacity to cope with stress is crucial for survival and also reproduction. The stress response differs in the various parts of an organism. Central corticotropin-releasing hormone (CRH) has been identified to be the main stress regulator. In the reproductive system, stress has a deleterious effect on reproduction and CRH is associated with dysfunction of the reproductive endocrine axis. Members of the CRH family have been detected in different reproductive organs of males and females. Ovarian CRH is probably involved in steroid biosynthesis and inflammatory like processes, ovulation and luteolysis. These effects are mediated via the CRH receptors CRH-R1 and CRH-R2. CRH-Rs are G protein-coupled receptors that drive different signalling pathways in the cell. In human, ligands for these receptors are CRH, urocortin 1, stresscopin-related peptide and stresscopin. This review gives an overview on the expression of the CRH family members in the ovary of mammals. Furthermore, potential CRH-induced signalling mechanisms in the ovary will be introduced.