DIETARY AND HYPOTHALAMIC CHANGES IN DELTA-4-ANDROSTENEDIONE-TREATED ZUCKER RATS

Dehydroepiandrosterone (DHEA) has been shown to alter hypothalamic mon oamines and reduce energy intake (EI) in Zucker rats (ZRs). We hypothe sized that a metabolite of DHEA, Delta 4-Androstenedione (Delta 4), ma y mediate these effects. Male lean and obese ZRs (LZR, OZR) were fed c ontrol chow (CC) for 7 days, during which basal EI was recorded, vario us concentrations of Delta 4 for 7 days, during which 0.6 and 0.3% Del ta 4 reduced EI significantly, and CC for 7 days, which resulted in a return of EI to basal levels. After Delta 4 administration, neurotrans mitter contents of various hypothalamic areas were determined. Seroton in (5-HT) has been shown to be correlated with feeding inhibition, and we have shown DHEA to increase lateral hypothalamic 5-HT synthesis; h owever, after 1 day and 7 days of Delta 4, the OZR exhibited an increa sed metabolism, not synthesis, of 5-HT in the lateral and paraventricu lar hypothalamus, respectively. Delta 4 was compared to DHEA in a macr onutrient self-selection study with female OZRs. One group was injecte d intraperitoneally (IP) with sesame oil (control), another with DHEA (100 mg/kg), and another with Delta 4 (100 mg/kg). Previous studies ha ve shown that DHEA decreases both EI and % calories from fat. In this study, Delta 4 decreased % calories from fat, but did not decrease tot al EI. Contrary to DHEA's effect of reducing serum insulin through 28 days of treatment, Delta 4 in chow reduced insulin only acutely (1 day ). We conclude, based on these differences, that DHEA has unique effec ts not mediated by its metabolite, Delta 4-Androstenedione. (C) 1997 E lsevier Science Inc.