Maternal insulin manipulations in rats organize body weight and noradrenergic innervation of the hypothalamus in gonadally intact male offspring.

In previous work it has been shown that adult male, but not female, offspring of rats that have been injected with protamine zinc insulin (6 IU/kg) on days 15-20 of gestation, develop significant obesity beginning about 50 days of age. This obesity is accompanied by elevated medial hypothalamic extracellular norepinephrine levels. To examine whether the expression of obesity in male offspring is mediated by perinatal testosterone levels, male offspring of insulin-treated or control dams were either castrated or received sham surgery on postnatal day 1. Castrated male offspring of insulin-treated dams did not become obese like their gonadally intact male littermates. This suggests that perinatal testosterone levels may interact with developmental processes mediating the obesity in male offspring of insulin-treated dams. A second question addressed was whether the elevated hypothalamic extracellular norepinephrine levels observed in our earlier work are evident as morphological changes in norepinephrine-containing systems in the medial hypothalamus and locus coeruleus. We found a significant enhancement of dopamine-beta-hydroxylase immunoreactivity in fibers innervating the paraventricular nucleus of the hypothalamus in 121-day-old, gonadally intact male offspring of insulin-injected dams. This suggests that the impact of maternal insulin injections on offspring obesity may be mediated through its organizing action on feeding-related fibers in the paraventricular nucleus.