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Effects of a brain-enhanced chemical delivery system for estradiol on body weight and serum hormones in middle-aged male rats.

We have developed a redox-chemical delivery system for brain-enhanced drug delivery of estradiol based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Estradiol, when combined with the carrier, readily crosses the blood-brain barrier and upon oxidation of the carrier is "locked" in the brain. The aim of this study was to evaluate the effects of the estradiol-chemical delivery system (E2-CDS) on body weight change and associated alterations in the secretion of anterior pituitary hormones in middle-aged, male rats. The data revealed that rats receiving E2-CDS exhibited a significant weight loss by 2 days which continued to day 14, the last observation day. A significant weight difference was observed between E2-CDS and DMSO-treated animals. Serum estradiol levels of rats treated with E2-CDS were elevated 100-fold by day 1 and decreased thereafter and serum prolactin concentrations were doubled by 24 hours and continued to increase to the completion of the experiment. Testosterone levels were markedly suppressed by 24 hours while serum levels of LH, TSH, T3, T4 and GH were not significantly altered. These data indicate that the E2-CDS causes a long-term reduction in body weight and testosterone secretion and that these changes are not mediated by alterations in the secretion of anterior pituitary hormones.