Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 28 P316

SFEBES2012 Poster Presentations Steroids (33 abstracts)

Impact of prenatal androgens on glucocorticoid metabolism in an ovine model of PCOS.

Saraid McIlvride 1 , Alicia Ellison 1 , Kirsten Hogg 2 , Alan McNeilly 2 , Colin Duncan 2 & Anthony Michael 1

1Division of Biomedical Sciences, St.George's University of London, London, United Kingdom; 2MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.

Within target cells, cortisol-cortisone inter-conversion is catalysed by both a NADP(H)-dependent, bidirectional type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme and by a NAD+-dependent, unidirectional type 2 11βHSD (11βHSD2) isoenzyme. Since several published studies have reported altered glucocorticoid metabolism in polycystic ovary syndrome (PCOS), the current study assessed whether prenatal exposure of lambs to testosterone propionate (TP) in an established ovine model of PCOS could programme altered postnatal cortisol oxidation. Fetuses were exposed to vehicle or TP administered either by direct injection (20 mg; days 62 and 72 of gestation) or via maternal injection (100 mg twice weekly; days 62 to 102 of gestation). Placental tissue (n=30), collected at D90 gestation, and adrenal glands (n=10) and visceral adipose tissue (n=42) harvested at postnatal weeks 10 to 12 were homogenized in phosphate-buffered saline. 11βHSD activities were subsequently quantified over 0.5, 1 or 24 hours, respectively, using a radiometric conversion assay with 100 nM [3H]-cortisol plus 4 mM NADP+ or NAD+. In male (but not female) lambs, fetal (but not maternal) injection of TP in mid gestation doubled the NAD+-dependent oxidation of cortisol in visceral adipose tissue (P<0.05) without affecting NADP+-dependent dehydrogenase activities. Irrespective of the route of injection, gender of the lamb or enzyme co-substrate, there was no significant effect of prenatal TP on cortisol oxidation in adrenal or placental tissue. Hence, we conclude that prenatal exposure to TP (administered to male lambs via fetal injection) selectively programmes increased enzymatic inactivation of cortisol by 11βHSD2 in visceral adipose tissue without affecting adrenal or placental 11βHSD2 activities. It remains to be established whether this response to prenatal androgen exposure might contribute to the altered glucocorticoid metabolism observed in some patients with PCOS.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: This work was supported by the Medical Research Council (grant number G0500717), the Scottish Funding Council (through a Scottish Senior Clinical Fellowship), a University of Edinburgh College of Medicine and Veterinary Medicine studentship and the Society for Endocrinology (summer studentship).

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