Neonatal hypothalamic androgenization in the female rat induces changes in peripheral insulin sensitivity and adiposity function at adulthood.

UNLABELLED: It is recognized that there exists a link between hyperandrogenicity and insulin resistance.

OBJECTIVE: By using the neonatally androgenized female rat we explored whether this treatment modifies peripheral insulin sensitivity and visceral fat function at adulthood.

EXPERIMENTAL DESIGNS: On day 5 of age, female Sprague-Dawley pups were injected, sub cutaneous, with either 50 ml of sterile corn oil alone (CT) or containing 1.25 mg of testosterone propionate (TP) and further used for experimentation on day 100 of age. CT and TP rats were killed by decapitation in non-fasting condition and blood samples were kept frozen for measurement of different metabolites. Immediately after sacrifice, freshly dissected visceral fat pads were used for isolation of adipocytes, these cells were then incubated with medium alone or containing different concentrations of insulin in order to determine leptin secreted into the medium. Additionally, in vivo metabolic responses to intravenous high glucose load were performed in, 24 hour-fasting, CT and TP rats.

RESULTS: We found that neonatal androgenization induced adult animals displaying higher visceral adiposity mass, body weight and leptinemia than CT rats. No group differences were found in basal circulating levels of several hormones and metabolic parameters. The results of the high glucose load 90-min test indicated that TP and CT rats developed similar glycemia but this accounted because of an early significantly higher peak values of circulating insulin in TP than in CT rats, regardless of similar enhancement in circulating glucocorticoid concentrations in both groups. While high glucose load significantly increased, over the baseline, circulating leptin concentrations as early as 30 min post-glucose in CT rats, in TP animals, it significantly enhanced leptinemia only by the end of the test. Finally, results of in vitro incubations of isolated visceral adipocytes indicated that cells from androgenized rats spontaneously released more leptin than control cells, although they were less responsive than CT cells to insulin-induced leptin output.

CONCLUSION: Our study strongly supports the hypothesis that development of insulin resistance seems to be dependent on early hyperandrogenicity.