The pancreas is altered by in utero androgen exposure: implications for clinical conditions such as polycystic ovary syndrome (PCOS)

• Published in: PloS one 2013-02, Vol.8 (2), p.e56263
• Main Authors: Rae, Mick, Grace, Cathal, Hogg, Kirsten, Wilson, Lisa Marie, McHaffie, Sophie L, Ramaswamy, Seshadri, MacCallum, Janis, Connolly, Fiona, McNeilly, Alan S, Duncan, Colin
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Androgen receptors; Androgens; Androgens - administration & dosage; Androgens - pharmacology; Animals; Apoptosis; Biology; Diabetes; Diethylstilbestrol; Drugs; Endocrinology; Estradiol - metabolism; Estrogens; Estrogens - pharmacology; Exposure; Female; Females; Fetus - drug effects; Fetus - embryology; Fetus - metabolism; Fetus - pathology; Fetuses; Gene expression; Gene Expression Regulation, Developmental - drug effects; Genes; Gestation; Glucose; Glucose tolerance; Homeostasis; Hyperinsulinemia; Injection; Insulin; Insulin - metabolism; Insulin resistance; Insulin secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Intrauterine exposure; Male; Maternal Exposure - adverse effects; Medical research; Medicine; Metabolism; Offspring; Pancreas; Pancreas - drug effects; Pancreas - embryology; Pancreas - metabolism; Pancreas - pathology; Physiology; Polycystic ovary syndrome; Polycystic Ovary Syndrome - embryology; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - pathology; Polymerase chain reaction; Pregnancy; Pregnant women; Progeny; Propionic acid; Receptor mechanisms; Receptors; Reproductive health; Rodents; Secretion; Sex hormones; Sheep; Signal Transduction - drug effects; Signaling; Social sciences; Studies; Testosterone; Testosterone propionate; Testosterone Propionate - administration & dosage; Testosterone Propionate - pharmacology; Western blotting; Womens health; Xenoestrogens
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056263

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