Searchable abstracts of presentations at key conferences in endocrinology

ea0012oc20 | Pituitary, ovary and steroids | SFE2006

Novel activation of MAPK family proteins in pituitary GH3 somatotrophs and alphaT3-1 gonadotrophs by C-type natriuretic peptide (CNP)

Jonas KC , Thompson IA , Chand AN , Fowkes RC

In target tissues, CNP acts via the cell surface guanylyl cyclase B (GC-B) receptor to stimulate cGMP accumulation. Transgenic mice studies deleting either CNP or the GC-B receptor suggest a role for CNP in regulating bone formation and pituitary growth hormone secretion. Our previous studies have implicated a role for CNP in inhibiting calcium transients in alphaT3-1 pituitary gonadotroph cells; however the biological consequence of cGMP accumulation remains unclear. Therefor...

ea0012oc2 | Young Endocrinologist prize session | SFE2006

Combinatorial signalling and gene transcription in neuroendocrine cells: does PACAP potentiate hormone-dependent gene transcription?

Monger JK , Patel MV , Jonas KC , Fowkes RC

The neuropeptide PACAP regulates numerous endocrine functions such as growth, metabolism and reproduction. In pituitary gonadotrophs, PACAP acts as a potent stimulator of gonadotrophin gene transcription and secretion, and potentiates the stimulatory effects of GnRH. We have examined the combinatorial effects of PACAP with GnRH or other activators of GnRH-signalling pathways in mouse αT3-1 gonadotroph and rat PC12 phaeochromocytoma cells. αT3-1 cells transiently tran...

ea0012p95 | Reproduction | SFE2006

Characterisation of 11β-hydroxysteroid dehydrogenase (11βHSD) expression and activity in the pre- and post-pubertal porcine (sus scrofa) testis and male reproductive tract

Sharp V , Fowkes RC , Thurston LM , Michael AE

Cortisol is metabolised by 11β-hydroxysteroid dehydrogenase enzymes (11βHSD1 and 11βHSD2). In immature rat Leydig cells, 11βHSD1 acts as an oxo-reductase whereas, after puberty, the dehydrogenase activity of 11βHSD1 predominates. In adult rats, 11βHSD1 is also highly expressed in caput epididymis, vas deferens and vesicular glands. Recently, 11βHSD1 mRNA and activities have been reported in post-pubertal pig testis. The objective of this stud...

ea0011oc3 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

Activation of cAMP (cAMP) binding protein (CREB) by gonadotrophin-releasing hormone (GnRH) requires calcium influx and PKC activity in gonadotroph cell lines

Jonas KC , Thompson IA , Burrin JM , Fowkes RC

The ubiquitous transcription factor, CREB, is responsible for mediating gene transcription in many endocrine tissues. Recent studies reveal that the activation of several signalling pathways can lead to the phosphorylation of CREB at Ser133, including PKC, MAPKs, CaMKs, and PI3K. In the pituitary gonadotroph, there are consensus cAMP response elements (CREs) in several of the gonadotrophin subunit promoters as well as in the GnRH receptor promoter. We have previously shown tha...

ea0008oc20 | Young Endocrinologist Session | SFE2004

Sp1/Sp3, GnRH and PACAP involvement in C-type natriuretic peptide (CNP/Nppc) expression and action in gonadotrophs

Fowkes RC , Burrin JM , McArdle CA , Steinhelper ME

C-type natriuretic peptide (CNP) is encoded by the Nppcgene and is abundant in the hypothalamus and anterior pituitary gonadotrophs. Nppc deletion leads to skeletal deformity, dwarfism, early death and female infertility. To investigate regulation of Nppcexpression and action in the hypothalamic-pituitary-gonadal axis, we investigated transcriptional regulation of the Nppc promoter in alphaT3-1 gonadotroph cells by transient transfection of reporter...

ea0012oc24 | Pituitary, ovary and steroids | SFE2006

Influence of C-type natriuretic peptide (CNP) on cell proliferation in αT3-1 gonadotrophs and GH3 somatotrophs

Thompson IR , Jonas KC , Wolf S , Lawson C , Wheeler-Jones CP , Fowkes RC

C-type natriuretic peptide (CNP) acts via its specific membrane-bound guanylyl cyclase receptor, GC-B, to stimulate cGMP production. Stimulation of cGMP impinges upon PKG and PKA signalling, leading to cell proliferation and cell cycle events. In endothelial cells, CNP is thought to perform a predominantly anti-mitogenic role, but the role of CNP on cell proliferation, cell cycle and DNA synthesis in pituitary cell lines has yet to be established. Using the mouse gonadotroph-d...

ea0008oc11 | Neuroendocrinology and Reproduction | SFE2004

Brain-derived neurotrophic factor (BDNF) is a novel steroidogenic factor-1 (SF-1) target gene in the ventromedial hypothalamus (VMH): implications for obesity onset

Fowkes RC , Tran PV , Akana SF , Carey CR , Dallman MF , Ingraham HA

BDNF, a neurotrophin involved in brain development and plasticity, is implicated in the melanocortin regulation of obesity onset. Mice deficient in the orphan nuclear receptor SF-1 have a poorly developed VMH and consequent absence of BDNF in this region. Our studies reveal a role for SF-1 in BDNF expression, and its' implications for hypothalamic obesity. Real-time RT-PCR indicated expression of BDNF exons I, III and IV were dramatically reduced in the VMH of SF-1 heterozygou...