Searchable abstracts of presentations at key conferences in endocrinology

ea0077p102 | Reproductive Endocrinology | SFEBES2021

Differentially glycosylated FSHR ligands as potential modulators of FSHR quaternary complexes and FSHR-dependent signalling

Agwuegbo Uche , Colley Emily , Bousfield George , Albert Anthony , Jonas Kim

The G protein-coupled receptor, follicle-stimulating hormone receptor (FSHR), is essential for reproduction. A key drug target of IVF, understanding the mechanisms modulating FSHR functions remains of high importance. The endogenous ligand of the FSHR, FSH, is a heterodimeric glycoprotein hormone with two predominant glycoforms identified. Partially glycosylated FSH21 has faster binding kinetics to the FSHR and more potent at activating cAMP-dependent signal pathways, in compa...

ea0086op3.4 | Reproductive and Neuroendocrinology | SFEBES2022

Identification and characterisation of novel follicle-stimulating hormone receptor antagonists

Duyen Tran Hanh , Agwuegbo Uche , Albert Anthony , Jonas Kim

Follicle-stimulating hormone receptor (FSHR) is a Class A G protein-coupled receptor (GCPR) that is essential in reproduction. Interactions with its heterodimeric glycoprotein hormone, FSH, activates the cAMP/PKA signalling pathway, which induces steroidogenic activity and granulosa cell proliferation to support ovarian follicle growth and survival. Moreover, a number of ageing-related extragonadal roles of FSH/FSHR have been proposed, with menopausal elevation in FSH linked t...

ea0086p119 | Reproductive Endocrinology | SFEBES2022

FSH glycosylation variants differentially modulate FSHR trafficking

Agwuegbo Uche , Richardson Rachel , Albert Anthony , Hanyaloglu Aylin , Jonas Kim

The Class A G protein-coupled receptor (GPCR), follicle-stimulating hormone receptor (FSHR), and its associated heterodimeric glycoprotein hormone (FSH) are essential for reproduction. As such, they’re key targets of assisted conception. Post-translational modification of FSH gives rise to two predominant glycosylation variants, which are modulated with ageing: partially glycosylated FSH (FSH21/18), predominates in women’s reproductive prime (20’s), displays fas...

ea0086p121 | Reproductive Endocrinology | SFEBES2022

Tool development for the in vivo analysis of the physiological role of FSHR oligomerisation

Johnson Gillian , Hopkins Thomas , Agwuegbo Uche , Bousfield George , Jonas Kim

G protein-coupled receptors are the largest family of mammalian receptors, with key roles in controlling most physiological processes. Ovarian function is no exception, with a key ovarian GPCR, follicle stimulation hormone receptor (FSHR), and its endogenous ligand, FSH, critical for pre-antral-antral follicle growth and survival. An increasingly important way that GPCRs have been shown to regulate ligand specificity and signal amplitude is via association and formation of dim...

ea0065p348 | Reproductive Endocrinology and Biology | SFEBES2019

Impact of a FSHR positive allosteric modulator on FSH glycosylation variant-dependent FSHR homomerisation and signal pathway activation

Agwuegbo Uche , Albert Anthony , Bousfield George , Jonas Kim

The heterodimeric pituitary glycoprotein hormone, follicle-stimulating hormone (FSH) and its target G protein-coupled receptor (FSHR) are essential for reproduction. As an important drug target for IVF, the need for more effective treatment drives interest in understanding what modulates FSH/FSHR functions. In vivo, two predominant FSH glycosylation variants have been identified; partially glycosylated FSH (FSH21) has faster binding kinetics to the FSHR and is more potent at a...

ea0094oc4.6 | Reproductive Endocrinology | SFEBES2023

Tool development: Characterization of novel follicle-stimulating hormone receptor (FSHR) Inhibitors

Xu Ruijuan , Sureshkumar Sumetha , Agwuegbo Uche , Tran Hanh , Hopkins Thomas , Bousfield George , Jonas Kim

Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein hormone, crucial for regulating female reproduction. Its actions are mediated through FSHR, a Class A G protein-coupled receptor (GPCR), which primarily couples to Gs/cAMP/PKA pathway to modulate ovarian follicle growth, granulosa cell proliferation, and estrogen production. In addition to dogmatic functions of FSH in reproduction, there is increasing evidence that FSH can act on extragonadal tissues. Specifica...