Transient prenatal androgen exposure produces metabolic syndrome in adult female rats

Abstract

Androgen exposure during intrauterine life in nonhuman primates and in sheep results in a phenocopy of the reproductive and metabolic features of polycystic ovary syndrome (PCOS). Such exposure also results in reproductive features of PCOS in rodents. We investigated whether transient prenatal androgen treatment produced metabolic abnormalities in adult female rats and the mechanisms of these changes. Pregnant dams received free testosterone or vehicle injections during late gestation, and their female offspring were fed regular or high-fat diet (HFD). At 60 days of age, prenatally androgenized (PA) rats exhibited significantly increased body weight; parametrial and subcutaneous fat; serum insulin, cholesterol and triglyceride levels; and hepatic triglyceride content (all P < 0.0125). There were no significant differences in insulin sensitivity by intraperitoneal insulin tolerance test or insulin signaling in liver or skeletal muscle. HFD had similar effects to PA on body weight and composition as well as on circulating triglyceride levels. HFD further increased hepatic triglyceride content to a similar extent in both PA and control rats. In PA rats, HFD did not further increase circulating insulin, triglyceride, or cholesterol levels. In control rats, HFD increased insulin levels, but to a lesser extent than PA alone ( approximately 2.5- vs. approximately 12-fold, respectively). We conclude that transient prenatal androgen exposure produces features of the metabolic syndrome in adult female rats. Dyslipidemia and hepatic steatosis appear to be mediated by PA-induced increases in adiposity, whereas hyperinsulinemia appears to be a direct result of PA.

Prenatal androgen excess programs metabolic derangements in pubertal female rats

“…A study of female sheep prenatally treated with testosterone found increased mRNA expressions of the IRS1 and GSK3 genes in skeletal muscles and the IRS2, PI3K, and AKT genes in adipose tissue (Nada et al 2010). In a rodent study, no difference was found in the expression levels of the IR, IRS1, IRS2, and AKT proteins in the skeletal muscles or liver, after prenatal testosterone exposure (Demissie et al 2008). These conflicting observations may result from differences between the action of DHT and testosterone, interspecies differences, and the expression of phosphorylated protein distinct from mRNA in insulin signaling pathway.…”

Correlation between Digit Length Ratios and Risk Factors Associated with Metabolic Syndrome

“…PCOS is the number one cause of infertility in premenopausal women, and frequently women with PCOS have metabolic diseases such as hypertension and insulin resistance [1]. Interestingly, treatment of various animals prenatally with testosterone produces the metabolic as well as reproductive disorders associated with PCOS [2][3][4][5][6][7][8][9]. The metabolic defects associated with prenatal androgen exposure are not limited to females, but are also seen in males [2,10,11].…”

Hyperprolactinemia induced by hCG leads to metabolic disturbances in female mice

“…The influence of androgens on lipid metabolism was also demonstrated in female rats under prenatal androgen treatment, which developed dyslipidemia and hepatic steatosis in adulthood. These changes would be the consequence of increased adipose tissue and insulin resistance induced by prenatal androgenization (Demissie et al 2008). A similar metabolic alteration has been described in adult rats following early postnatal administration of testosterone (Alexanderson et al 2007).…”