Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring.

In previous work it has been shown that adult male, but not female, offspring of rats that have either been injected with Protamine Zinc Insulin on days 15-20 gestation, or undernourished during the first 2 weeks of gestation, develop significant obesity commencing at about 50 days of age. The present experiment examines the question of whether rats with these two forms of obesity display neurochemical abnormalities in areas of the brain known to influence food intake and body weight. Twenty-one gauge stainless steel guide shafts were surgically implanted using standard stereotaxic procedures. One week later 26 ga microdialysis probes were lowered into the medial hypothalamus. Dialysates collected from male offspring in the two experimental conditions contain significantly higher norepinephrine (NE) levels than did controls. It would appear that in addition to sharing a similar time course of onset and a sex dependent expression of obesity, both of these models are also characterized by elevated medial hypothalamic NE. Since this obesity appears only in males, and at a time when testosterone levels are rapidly rising in males, and since testosterone has been shown to elevate food intake and body weights in rats, we also investigated whether gonadal weights or circulating testosterone levels were differentially elevated by our manipulations.