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...

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 ...

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...

ea0065oc6.2 | Reproductive Endocrinology and Biology | SFEBES2019

Differential follicle stimulating hormone glycosylation modulates follicle growth and survival rates

Johnson Gillian , Bousfield George , Hardy Kate , Jonas Kim

Ovarian aging is a naturally occurring physiological process, marked by dynamic changes in ovarian function and hormone secretion. Ovarian ageing is associated with several co-morbidities, including; osteoporosis, diabetes, cardiovascular disease and impaired cognitive function, therefore, understanding the physiological processes regulating this is imperative for identifying novel treatment modalities. A key endocrine regulatory of ovarian function is the heterodimer glycopro...

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...

ea0094op3.3 | Reproductive Endocrinology | SFEBES2023

Characterisation of a novel N terminally FLAG-tagged FSHR knock in mouse model to understand the physiological roles of FSHR oligomerisation

Hopkins Thomas , Johnson Gillian , Sureshkumar Sumetha , Bousfield George , Jonas Kim

The G protein-coupled receptor (GPCR), follicle stimulating hormone receptor (FSHR) plays a critical role in ovarian function and reproduction, with multiple functions in follicle growth, maturation, survival, and steroid hormone production. Yet how FSH/FSHR mediates these pleiotrophic physiological roles remains unknown. Numerous studies indicate GPCRs can regulate and diversify their actions through receptor-receptor association and the formation of dimers/oligomers. Moreove...