Endocrine Abstracts

The classical model of GPCR activation entails the binding of a single ligand to a single receptor molecule, followed by transmembrane signal transduction to the appropriate G protein(s). The possibility of GPCRs functioning as dimers or oligomers still remains controversial, and is largely based on in vitro studies on transfected cells. The glycoprotein hormone receptors, including that of LH (LHCGR), differ from most GPCRs by their large extracellular ligand-binding...

G protein-coupled receptors (GPCRs) are one of the largest families of the mammalian genome, mediating the effects of approximately 40% of prescribed drugs. Until recently, accepted dogma stated that GPCRs exist as monomers, however, it is becoming evident that GPCRs can form higher order dimer/oligomer complexes which provide important mechanisms for the diversification of receptor function. The LHCGR is a class A family GPCR, primarily coupling to the Gαs pat...

Spermatozoa are dependent on the proximal epididymis environment to complete their maturation. However, no single specific factor crucial for this process has been identified. Rnase9 and Rnase10 are expressed specifically in the murine proximal epididymis. Located on chromosome 14C1 only 28 kb apart, they do not show high homology with each other. An orthologue of both genes exist in the rat and human, and ‘Train A’ (porcine orthologue) is the most abun...

A common polymorphism of the ERβ gene (AluI) located in 3′-UTR of exon 8 has been shown to be associated with clinical features of altered estrogen action in tissues where this gene is expressed. It has recently been shown that GnRH neurons express ERβ, indicating that this receptor may participate in the feedback regulation of gonadotrophin secretion. We therefore studied the association of gonadotrophin levels and the AluI polymorp...

Hypersecretion of hCG in transgenic mice produces profound alterations in the ovary, thus triggering failures in ovulation and affecting fertility. The objective of this study was to analyze the response of immature female mice overexpressing moderated (hCGβ+; 0.1 IU/ml) and elevated (hCGαβ+; 7 IU/ml) levels of hCG to an ovulation induction protocol (PMSG 7.5 IU i.p.; after 48 h, hCG 7.5 IU i.p). Wild-type (WT) females subjected to the same protocol were used as...

Strong gain-of-function mutations have not been identified in humans in the FSH receptor (FSHR), while such mutations are common among many other G-protein-coupled receptors. In order to predict consequences of such mutations on humans, D580 (D6.44) mutant forms of mouse (m) FSHR were expressed under the human anti-Müllerian hormone promoter in transgenic mice. Transgenic expression of mFshrD580H in granulosa cells led to abnormal ovarian structur...

FSH receptor (FSHR) expression has been shown in gonadal tumours, as well as in endothelial tumour vessel cells of various cancers. FSHR, due to its transmembrane localization could be a good candidate for receptor-mediated targeted cancer therapy. In recent years, a number of membrane disrupting lytic peptides have been used for receptor-based cancer therapy. In the present study, we characterised the specificity and cytotoxicity of a lytic peptide Phor21 conjugated to three ...

Progesterone (P4) treatment has been shown to have a clear modulating effect on murine Leydig tumor cell (mLTC-1) function, including downregulation of luteinizing hormone receptor. We hypothesized that P4 would stimulate, whereas an antiprogestine mifepristone (MF) block tumor progression in vivo in a transgenic (TG) murine Leydig cell tumor model (inhibin-α promoter-driven SV40 T-antigen (inhα/Tag)) and act similarly on cell proliferation in vitro...

Antiprogestine mifepristone (MF) has been shown to inhibit ovarian epithelial cancer (OEC) cell growth in vitro and in vivo. Recent clinical trials with MF for human OEC were unsuccessful, for unknown reasons. Progesterone (P4) is believed to have preventive measures towards breast, endometrial or hOEC cancers. Hereby we analyzed the effects of P4 and MF on ovarian granulosa cell tumorigenesis (GCT) in vitro and in vivo...

The LH receptor (LHR) is a 7-transmembrane domain G-protein coupled receptor (GPCR) mainly expressed in the gonads with a major role in the development and maintenance of gonadal steroidogenesis and gametogenesis. Its ligand LH, secreted by the pituitary gland, binds to the extracellular domain of LHR triggering a conformational change in the transmembrane domain and leading to activation of intracellular signalling cascades.As a member of the GPCR famil...