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Endocrine Abstracts (2017) 49 S25.3 | DOI: 10.1530/endoabs.49.S25.3

ECE2017 Symposia HPA axis regulation during a woman's life: impact on metabolic outcomes (3 abstracts)

11β-hydroxysteroid dehydrogenase activity, androgen excess, and metabolic outcomes in woman

Jeremy Tomlinson


UK.


Steroid hormones have potent metabolic effects. Glucocorticoid excess is characterized by central adiposity, insulin resistance, type 2 diabetes and increased cardiovascular risk. Whilst endogenous glucocorticoid excess is rare, local tissue-specific availability of glucocorticoid is controlled by a series of enzymes that are, at a pre-receptor level, able to regulate cortisol’s ability to bind and activate the glucocorticoid receptor. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone to active cortisol, and therefore amplifies local glucocorticoid action. It is highly expressed in key metabolic target tissues including liver, fat and muscle and is dysregulated in metabolic disease including polycystic ovarian syndrome. It has been a target for therapeutic intervention and selective 11β-HSD1 inhibitors provide modest metabolic improvements in patients with type 2 diabetes. In parallel, the A-ring reductases, (5α- and 5β-reductase), inactivate glucocorticoids, but importantly, the isoforms of 5α-reductase convert testosterone to the more potent androgen, dihydrotestosterone. 5α-reductase activity is increased in patients with PCOS and may contribute significantly to the androgen excess observed in these patients and fuel their adverse metabolic phenotype. In addition, adipose tissue is able to generate androgens through the activity of 17β-hydroxysteroid dehydrogenase type 5 (AKR1C3), and activity and expression are increased in patients with obesity and PCOS. In vitro data suggest that AKR1C3 may drive lipid accumulation locally within adipocytes through enhanced androgen generation. In conclusion, pre-receptor steroid hormone metabolism has a powerful role to play in the regulation of metabolic phenotype in patients with PCOS and offers significant potential as a target for therapeutic intervention.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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