WCRB2014 POSTER PRESENTATIONS (1) (335 abstracts)
Fetal overexposure to androgens, not estrogens, leaves a permanent legacy in terms of adrenal function in offspring
Seshadri Ramaswamy 1 , Cathal Grace 1 , Forbes Howie 1 , Fiona Connolly 2 , Julia Konovalova 1 , Alan S McNeilly 2 , W Colin Duncan 2 & Mick Rae 1
1Edinburgh Napier University, Edinburgh, UK; 2University of Edinburgh, Edinburgh, UK.
Introduction: Overexposure to androgens during fetal life creates offspring with a polycystic ovary syndrome (PCOS)-like phenotype. Whether this phenotype is attributable to androgens during fetal life, or estrogens via maternal/placental metabolism, remains uncertain. The potential for in utero steroidal disruption of adrenal development and function is also unclear. We have examined the adrenal during development and adulthood in response to in utero androgenic and estrogenic over-exposure.
Methods: Ovine female fetuses were injected with 20 mg of testosterone propionate (TP) or diethylstilbesterol (DES) at days 62 and 82 of gestation, then sacrificed at day 90. A subset were carried to term and conventionally reared until 1 year old. Steroidogenic gene expression (qRT-PCR) was assessed in fetal and postnatal adrenals and cortisol and testosterone secretion in response to a Synacthen challenge was determined by ELISA and RIA respectively.
Results and discussion: During fetal life DES increased CYP11B1 mRNA; P<0.05. During adulthood, prenatal TP was associated with elevated mRNA concentrations of STAR, CYP11B1, CYP21A, HSD3B1, and HSD17B1 (P<0.05), whereas fetal DES treatment was associated with decreased ACTH-receptor, CYP11A1 and HSD17B1 mRNA expression (P<0.05). Cortisol secretion in response to Synacthen stimulation was unaffected by either prenatal treatment, and DES had no effect on testosterone secretion. However, adrenal testosterone secretion was elevated 30 min post stimulation in animals prenatally exposed to TP (untreated: 0.46±0.18 vs prenatal TP: 1.538±0.18 ng/ml; P<0.0001). Female fetal androgen over-exposure is associated with increased adrenal androgen secretion in offspring, supporting fetally programmed adrenal hyperandrogenism in PCOS.
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ISSN 2052-1472 (online)
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