The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)

Franks, Stephen; Rae, Mick T; Grace, Cathal; Hogg, Kirsten; Wilson, Lisa Marie; McHaffie, Sophie L; Ramaswamy, Seshadri; MacCallum, Janis; Connolly, Fiona; McNeilly, Alan S; Duncan, Colin

Abstract

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P

Citation

Franks, S., Rae, M. T., Grace, C., Hogg, K., Wilson, L. M., McHaffie, S. L., …Duncan, C. (2013). The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS). PLOS ONE, 8(2), https://doi.org/10.1371/journal.pone.0056263

• Journal Article Type: Article
• Acceptance Date: Jan 7, 2013
• Online Publication Date: Feb 15, 2013
• Publication Date: Feb 15, 2013
• Deposit Date: Mar 27, 2014
• Publicly Available Date: Mar 27, 2014
• Print ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 2
• Article Number: e56263
• DOI: https://doi.org/10.1371/journal.pone.0056263
• Keywords: polycystic ovary syndrome (PCOS); insulin signalling; pancreatic morphology; quantitative (Q) RT-PCR; western blotting; androgen over-exposure
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/6686
• Publisher URL: http://dx.doi.org/10.1371/journal.pone.0056263