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Current research interests
My research focuses on the hormonal regulation of gene expression, particularly identification of the intracellular signalling pathways activating transcription factors and their role in peptide-regulated hormone gene transcription. This work has predominantly been performed in pituitary cells and has contributed to knowledge of pituitary physiology and pathology. Recent studies have investigated the role of the nuclear receptor SF-1 in the transcriptional regulation of the human glycoprotein hormone αSU by PACAP and GnRH in gonadotrophs. Our results demonstrated the dependence of basal, PACAP and GnRH-stimulated αSU gene transcription on the SF-1 binding site in αT3-1 gonadotrophs and enhanced serine phosphorylation of SF-1, probably via a MAP kinase dependent pathway. We are also investigating the cellular and molecular mechanisms underlying the actions of BMP-2 to induce gonadotroph-specific gene expression during pituitary development. We have shown differential receptor sub-type expression and differential activation of signalling pathways and identified a number of pituitary ontogenic genes that are transcriptionally regulated by BMP-2. Our studies of SF-1 have been extended to its potential role in other tissues such as skin and the expertise of the group in MAP kinase signalling and transcription factors has led to two collaborative studies, one with Professor Hough’s group at Stellenbosch University, SA to investigate the mechanism of action of protein tyrosine phosphatases in the pathogenesis of glucocorticoid-induced osteoporosis and another with Professor Philpott (Queen Mary, University of London) to examine the role of DAX-1 expression in keratinocyte differentiation and steroidogenesis.
Key publications
- Aganna E, Burrin JM, Hitman GA, Turner MD. Involvment of calpain and synaptotagmin Ca2+ sensors in hormone secretion from excitable endocrine cells. J Endocrinol (2006); 190(3): R1-7.
- Hanson PL, Aylwin SJB, Monson JP, Burrin JM. FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas. Eur J Endocrinol (2005); 152: 363-370
- Fowkes RC, Sidhu KK, Sosabowski JK, King P, Burrin JM. Absence of PACAP-stimulated transcription of the human glycoprotein a-subunit (aGSU) gene in LbT2 gonadotrophs reveals disrupted cyclic 3’5’-adenosine monophosphate (cAMP)-mediated gene transcription. J Mol Endo (2003); 31:263-278
- Fowkes RC, Desclozeaux M, Patel M, Aylwin SJB, King P, Ingraham HA, Burrin JM. Steroidogenic factor-1 (SF-1) and the gonadotrope specific element (GSE) enhance basal and pituitary adenylate cyclase-activating polypeptide (PACAP)-stimulated transcription of the human glycoprotein hormone a-subunit gene (aGSU) in gonadotropes. Molecular Endocrinology (2003); 17:2177-2188
- Hunter JAC, Skelly RH, Aylwin SJB, Geddes JF, Evanson J, Besser GM, Monson JP, Burrin JM. The relationship between pituitary transforming gene expression and in vitro hormone and vascular endothelial growth factor secretion from human pituitary adenomas. Eur J Endocrinol (2003); 148: 203-211.
- Siddiqi A, Parsons MP, Lewis JL, Monson JP, Williams GR, Burrin JM. Thyroid hormone receptor expression and function in human bone marrow stromal cells. J. Clin. Endocrinol. Metab. (2002); 87: 906-914
- Fowkes RC, King P, Burrin JM. Regulation of human glycoprotein hormone asubunit gene expression in LbT2 gonadotropes by protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2). Biology of Reproduction (2002); 67: 725-734
- Aylwin SJB, Welch JP, Davey CL, Geddes JF, Wood DF, Besser GM, Grossman AB, Monson JP, Burrin JM. The relationship between SF-1 and DAX-1 expression and in vitro gonadotropin secretion in human pituitary adenomas. J. Clin. Endocrinol. Metab. (2001); 86: 2476-2483
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