IMPRINTING OF FEMALE OFFSPRING WITH TESTOSTERONE RESULTS IN INSULIN-RESISTANCE AND CHANGES IN BODY-FAT DISTRIBUTION AT ADULT AGE IN RATS

In women, a relative hyperandrogenicity is statistically associated wi th insulin resistance and centralization of body fat, which are predic tors for the development of non-insulin-dependent diabetes mellitus, T he aim of this study was to evaluate the effect of androgenization of newborn female rats on insulin sensitivity at adult age, To mimic the neonatal androgen peak normally observed in male rats, female pups wer e administered one high dose of testosterone (T) subcutaneously within 3 h after birth, They were then given back to their mothers and follo wed to adult age, At the end of the week 9, tail samples were taken, s howing no differences in fasting plasma concentrations of glucose, lac tate, insulin, or free fatty acids between T-treated rats and controls , Plasma concentrations of T and progesterone were significantly lower in the T-treated rats, whereas no differences were found in the level s of corticosterone, estradiol, insulin-like growth factor I, or ACTH. After 10 wk, insulin sensitivity was studied with hyperglycemic and e uglycemic hyperinsulinemic (5 mU insulin/kg/min) clamp techniques, The T-treated rats showed insulin resistance with both techniques, which was overcome with time and increasing insulin concentrations during th e clamp measurements, The T-treated rats were also heavier and had inc reased relative weights of skeletal muscles and the spleen, Parametria l, retroperitoneal, and inguinal adipose tissues decreased in weight w hile mesenteric adipose tissue tended to increase, resulting in an sim ilar to 30-50% larger mesenteric than other adipose tissues, It is con cluded that neonatal T imprinting of female rats is followed by insuli n resistance, changes in adipose tissue distribution, and an enlarged lean mass, without elevation of circulating T, Similar changes are see n in adult female rats or women receiving T.