FOWKES LAB: Endocrine Signaling Group
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Natriuretic Peptides

The mammalian natriuretic peptides, ANP, BNP and CNP have well established effects on cardiovascular and bone biology. However, despite being expressed at high concentrations in the anterior pituitary, we have little understanding of what CNP does in regulating neuroendocrine function.

Our lab has several related projects investigating the neuroendocrine role of CNP; the first is to determine the developmental and functional role of CNP in pituitary gonadotrophs and somatotrophs. The second project uses the highly versatile Zebrafish (Danio rerio) to establish how CNP genes may affect neuroendocrine development. And, most recently, we have started to examine the roles of CNP in regulating the blood-brain-barrier and astrocyte function in particular. Click here for a link to our publications.

Natriuretic peptides & pituitary development and function
We have focussed on the anterior pituitary as a natriuretic peptide target tissue, for several years. Our initial BBSRC project grant, and subsequent Wellcome Trust and new BBSRC project grants, have expanded our molecular and pharmacological understanding of what CNP does in the anterior pituitary. In collaboration with Dr Imelda McGonnell, we have developed several Zebrafish models to try to understand the role of CNP in pituitary development, and in the function of the mature pituitary gland. Our clinical collaborators, Dr Olaf Ansorge (John Radcliffe Hospital, Oxford), Prof. John Wass (OCDEM, Churchill Hospital, Oxford), along with reproductive biologist specialist, Prof Alan McNeilly (University of Edinburgh), have assisted our studies into pituitary natriuretic peptides by providing us with valuable clinical samples of human pituitary adenomas as well as normal foetal pituitary tissue.

Natriuretic peptides & GnRH signaling 
In related studies, we continue to examine the link between natriuretic peptides and gonadotrophin releasing hormone (GnRH) signalling. In collaboration with Prof. Craig McArdle (University of Bristol) and Prof. Mark Roberson (Cornell University), we've established that pulsatile GnRH causes different effects on the expression of the natriuretic peptide system in pituitary gonadotroph cells.

Natriuretic peptides & endothelial cell function
Our most recent development has been new projects that investigate the role of CNP in endothelial cells supporting the circulation, but also in the maintenance of the blood-brain-barrier. With our collaborator, Dr Charlotte Lawson, we are examining whether CNP can perform endothelial-protective effects, similar to those already identified in cardiac tissue and suggested to occur in renal tissue.


Comparative Endocrinology of companion animals
We have a growing interest in examining endocrine disorders and neoplasias in companion animals. Endocrine disorders are common in pets, with adrenal, thyroid and pituitary dysfunction being caused by a range of mechanisms. As human lifestyles have changes over the past 50 years, so have those of companion animals, and whilst it's important to research the causes and potential therapies in order to treat these dogs and cats as patients, a wider possibility exists - that these animals can serve as so-called 'sentinel species' to alert us to environmental disruption that impinges upon homeostasis and metabolism. 

​​We are very fortunate to have excellent collaborators to study endocrine neoplasias and metabolic disorders in small animals. We are investigating pituitary tumour incidence in cats and dogs, particularly the link between acromegaly and diabetes in the feline population, seen at the UK's only hypophysectomy clinic for cats, treating referral cases from across the country. We have successfully cultured feline pituitary adenomas following surgery, and have a bespoke molecular assay to examine natriuretic peptides, pituitary markers and tumours genes, in collaboration with consultant endocrinologist, Prof. Marta Korbonits, from Barts & The Royal London.  
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Glucocorticoids and Comparative Endocrinology

We have several projects that examine the HPA axis in humans, production and companion animals.  Most recently, we're embarking on studies in conjunction with Dr Rowena Packer and Prof. Holger Volk, to examine stress responses in epileptic dogs.

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