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Title: BMP3b expression and role in zonation and tumourigenesis in the adrenal cortex
Author: Sze, Wing-Chiu (Candy)
ISNI:       0000 0004 9355 524X
Awarding Body: Queen Mary University of London
Current Institution: Queen Mary, University of London
Date of Award: 2020
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The adrenal gland is a vital organ consisting of an outer cortex surrounding an inner medulla. The adrenal cortex has three zones: zona glomerulosa (zG), zona fasciculata (zF) and zona reticularis (zR) which synthesise the steroids aldosterone, cortisol and dehydroepiandrosterone, respectively. The adrenal gland responds to constant physiological changes to maintain homeostasis by rapidly producing hormones, such as cortisol during stress or aldosterone in hypotension. The factors that determine differentiation and zonation of the adrenal cortex are not fully understood, although there is consensus that adrenal stem/progenitor cells residing in the subcapsular region of the gland can differentiate to renew and remodel the gland according to steroidogenic requirements. Bone morphogenetic protein 3b (Bmp3b) was previously found in a rat microarray study to be exclusively expressed in the outer part of the adrenal cortex that contain capsular/zG cells. We have confirmed the findings of the microarray study and demonstrate that BMP3b acts locally to upregulate CYP11B2 (specific to zG) and in a gradient dependent manner to downregulate the expression of steroidogenic enzymes specific to zF and zR in H295R cell lines. This action of BMP3b is possibly through inhibition of BMP2 expression and activity. BMP2 was found to be most highly expressed in the inner cortex and was shown to upregulate the expression of zR specific enzymes. Animal experiments confirmed the presence of Bmp3b in the capsular region but indicated that Bmp3b knockout mouse did not have abnormal adrenal morphology. BMP3b expression was increased in some human adrenocortical carcinoma samples but this was not consistent across the cohort. Those tumours with increased expression of BMP3b correlated with a less aggressive histology. BMP3b could therefore potentially be used as a prognostic factor and help guide patient treatment and prognosis. This study demonstrates that BMP3b could play.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available