Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 38 P415 | DOI: 10.1530/endoabs.38.P415

SFEBES2015 Poster Presentations Steroids (49 abstracts)

Lineage conversion of human cells to an adrenocortical phenotype: a new technology to study the adrenal gland

Gerard Ruiz Babot 1 , Irene Hadjidemetriou 1 , Sharon Jane Ajodha 1 , David Taylor 2 , Norman Taylor 2 & Leonardo Guasti 1

1William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, London, UK; 2Department of Clinical Biochemistry, King’s College Hospital, London, UK.

The adrenal cortex is the primary site of steroid synthesis, producing glucocorticoids under the control of the hypothalamic–pituitary axis and mineralocorticoids under the control of the renin–angiotensin system.

Adrenal insufficiency, which can be life threatening, is cause by a number of adrenal disorders, and lifelong management of these patients with exogenous steroids can be challenging. No drug suitably mimics the diurnal pattern of cortisol noted in healthy individuals, and objective variables to measure replacement quality are lacking. Our long-term goal is to develop novel personalized and curative treatments that use stem cells to treat the many progressive and debilitating conditions affecting the adrenal cortex. The potential to produce and expand disease- and patient-specific cells may also revolutionize our understanding of the underlying pathophysiology of adrenal disorders, paving the way for the identification of novel therapeutic targets.

Steroidogenic factor 1 (SF1) is a transcription factor essential for both adrenal and gonadal development. SF1 not only binds to responsive elements in the promoter region of steroidogenic genes to positively regulate their transcription, but can be considered a true effector of cell fate as it starts a genetic program driving embryonic mesenchymal cells towards a steroidogenic phenotype/lineage; its absolute requirement for steroidogenesis has been recently demonstrated in vivo. Also, the capacity to impose an SF1-dependent steroidogenic-like gene expression program in a variety of murine cells (embryonic fibroblasts, adipose stromal fraction, bone marrow stroma, ES cells, and IPSCs) has been verified by several groups.

By forcing the expression of SF1, but not of other transcription factors involved in adrenal development, we demonstrate the ability of human fibroblasts, blood-derived late outgrowth endothelial progenitor cells (L-EPCs), and urine-derived stem cells (USCs) to lineage convert to steroidogenic-like cells, as assessed by changes in cell morphology, gene expression, activation of adrenal-specific signaling pathways, and hormonal output.

Volume 38

Society for Endocrinology BES 2015

Edinburgh, UK
02 Nov 2015 - 04 Nov 2015

Society for Endocrinology 

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