Endocrine Abstracts

Prostaglandin E2 acts via 4 GPCRs, EP1-4. EP2 regulates inflammation and has important roles in cardiovascular function, reproduction, and malignancy. GPCR signalling and trafficking are highly integrated as signals from the endomembrane can exhibit distinct profiles from the plasma membrane. Whether EP2 activity is spatially regulated and if this is modified by ligand bias is currently unknown. In HEK 293 cells, three selective EP2 ligands, butaprost, AH13205, and PGN9856i, e...

The gonadotrophin receptors, luteinising hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR) are G-protein coupled receptors, vital in regulating reproductive functions. Whilst FSHR and LHR are known to form homomers, and have been recently shown to heterodimerise/oligomerise, the functional and physiological significance of LHR/FSHR heteromerisation remains elusive. This study aimed to explore the functional significance of LHR/FSHR crosstalk, exploring me...

G protein-coupled receptors (GPCRs) are the largest family of mammalian receptors, modulating most aspects of endocrine homeostasis. GPCRs can associate to form dimers and higher order oligomers, acting to diversify receptor functionality. Most studies have explored the functional significance of GPCR dimerization in vitro and we have recently demonstrated the functional relevance of GPCR dimerization in vivo. Using the LH receptor (LHR), we have shown that t...

LH receptor (LHR) is a G protein-coupled receptor (GPCR) that plays key roles in reproduction and pregnancy. Endocytic trafficking and sorting of GPCRs to diverse cellular fates represent a key mechanism in defining cellular responses by controlling both the temporal and spatial parameters of cellular signalling. How different processes within the endocytic system are coordinated, however, needs to be mechanistically dissected in more detail. We have recently demonstrated that...

It is well established that the interaction between an implanting embryo and the endometrium is essential for successful implantation and there is a variety of locally secreted factors within the uterine environment which underlies this maternal–fetal cross-talk. Human chorionic gonadotrophin (hCG) is a glycoprotein hormone secreted by the embryo and is essential during early stages of pregnancy to maintain progesterone production from the corpus luteum. Its receptor (LH/...

The gonadotrophin receptors, LH receptor (LHR) and FSH receptor (FSHR) are G-protein coupled receptors, vital in regulating reproductive functions. During the follicular phase of the ovarian cycle, FSHR and LHR are separately localised to discrete cellular compartments, granulosa and theca cells respectively, where they control steroidogenesis and follicle maturation. However, as the follicle develops, LHR expression is induced in granulosa cells, resulting in temporary co-exp...

The gonadotrophin receptors, LH receptor (LHR) and FSHR are G-protein coupled receptors, vital in mediating reproductive functions. During the follicular phase of the ovarian cycle, FSHR and LHR are separately localised to discrete cellular compartments, granulosa and theca cells respectively, where they control steroidogenesis and follicle maturation. However, as the follicle develops, LHR expression is induced in granulosa cells, resulting in co-expression of FSHR and LHR in...

The Hydroxycarboxylic Acid Receptor 1 (HCAR1) is a Gαi/o-coupled GPCR known to be activated by both L- and D-lactate; metabolites produced by gut microbiota and anaerobic metabolism. Elevated D-lactate levels are indicative of dysbiosis and inflammatory bowel disease. As lactate can be transported into cells, it has the potential to activate HCAR1 at the plasma membrane and within intracellular locations resulting in diversified responses. Whether HCAR1 signalling is spat...

Polycystic ovary syndrome (PCOS) is a multifactorial, complex endocrine disorder affecting a significant proportion of the global population. Hyperandrogenism is a key feature of PCOS patients. Aberrant secretion and/or action of gonadotropins have been implicated in PCOS, but, to date, we have only limited knowledge of how these factors may interact in the aetiology of PCOS. We hypothesised that excess androgens may cause aberrant gonadotropin activity and therefore sought to...

Defects in any of the four functional domains of the androgen receptor (AR) (resulting from loss-of-function or gain-of-function mutations), may affect androgen action. Specific AR splice variants have been reported in women with PCOS (Wang et al, PNAS 2015 112 4743). In this study we sought to identify AR splice variants in granulosa-lutein (GL) cells of women with and without PCOS and to assess their functional significance. GL cells were ...