Searchable abstracts of presentations at key conferences in endocrinology

ea0086p118 | Reproductive Endocrinology | SFEBES2022

Determining the impact of FSH glycosylation variants on the pre-antral follicle transcriptome in the ageing ovary

Johnson Gillian , Bousfield George , Jonas Kim

Ovarian ageing is a naturally occurring physiological process, marked by dynamic changes in ovarian function and hormone secretion. A key of ovarian regulator is follicle stimulating hormone (FSH). FSH is secreted as two glycosylation variants: partially glycosylated FSH (FSH21) and fully glycosylated FSH (FSH24). Analysis has shown that the ratio of FSH21:FSH24 changes with age, with FSH21 predominant during reproductive prime, and FSH24 predominant around menopause. How FSH ...

ea0065p357 | Reproductive Endocrinology and Biology | SFEBES2019

Deciphering the effects of testosterone on FSH glycosylation variant-dependent ERK/MAPK activation

Kellaway Jedidiah , Bousfield George , Jonas Kim

The heterodimeric glycoprotein hormone, follicle stimulating hormone (FSH) and its receptor (FSHR) are vital for reproductive function, driving ovarian function via follicular recruitment, selection and development. FSH exists as two predominant glycoforms in females; partially glycosylated (FSH21) and fully glycosylated (FSH24), based on differing glycosylation patterns of the β subunit. The FSH glycoforms have different bioactivities, with FSH21 displaying a higher bind...

ea0015p264 | Pituitary | SFEBES2008

Mechanism of C-type natriuretic peptide (CNP) stimulated phosphorylation of ERK-MAPK in pituitary GH3 somatotrophs

Jonas Kim , Thompson Iain , Fowkes Rob

CNP, the third peptide of the mammalian natriuretic peptide family, exerts its biological effects through activation of the guanylyl cyclase B (GC-B) receptor and resulting cGMP accumulation. Our previous studies reported that CNP stimulates phosphorylation of MAPK family proteins in GH3 somatotrophs. This present study aimed to further characterise the mechanism of CNP-stimulated ERK phosphorylation and resulting biological consequences in GH3 cells. Western blot analyses sho...

ea0077oc1.6 | Reproductive and Neuroendocrinology | SFEBES2021

Differential follicle stimulating hormone glycosylation modulates pre-antral follicle growth and survival rates

Johnson Gillian , Onabanjo Caitlan , Bousfield George , Hardy Kate , Jonas Kim

Ovarian ageing is a naturally occurring physiological process, marked by dynamic changes in ovarian function and hormone secretion. A key endocrine regulator of ovarian function is the heterodimeric glycoprotein hormone, follicle stimulating hormone (FSH). FSH is secreted as two glycosylation variants: partially glycosylated FSH (FSH21) and fully glycosylated FSH (FSH24). These variants have different in-vitro activities, with FSH21 more bioactive than FSH24. Interest...

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...

ea0050oc5.3 | Reproduction and Neuroendocrinology | SFEBES2017

Decoding the functional significance of follicle stimulating hormone glycosylation variants

Colley Emily , Wakefield Baylee , Bousfield George , Jonas Kim

FSH and its G protein-coupled receptor (FSHR) are essential for the coordination of reproductive functions. As such, they are a primary target of most assisted reproductive technologies, thus understanding the physiology regulating their function is paramount. Two naturally occurring glycoforms of FSH have been identified-hyperglycosylated FSH (FSH24) and hypoglycosylated FSH (FSH21), based on their ASN glycosylation pattern. The secretion of FSH21 and FSH24 has been shown to ...

ea0050oc5.3 | Reproduction and Neuroendocrinology | SFEBES2017

Decoding the functional significance of follicle stimulating hormone glycosylation variants

Colley Emily , Wakefield Baylee , Bousfield George , Jonas Kim

FSH and its G protein-coupled receptor (FSHR) are essential for the coordination of reproductive functions. As such, they are a primary target of most assisted reproductive technologies, thus understanding the physiology regulating their function is paramount. Two naturally occurring glycoforms of FSH have been identified-hyperglycosylated FSH (FSH24) and hypoglycosylated FSH (FSH21), based on their ASN glycosylation pattern. The secretion of FSH21 and FSH24 has been shown to ...

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...