Diabetes-related changes in brain beta adrenoreceptors in rats as assessed by quantitative autoradiography: Relationship to hypothalamic norepinephrine metabolism and pituitary-gonadal hormone secretion

Streptozotocin (STZ)-induced diabetes produced significant and selective alterations in brain beta adrenoreceptor subtypes, norepinephrine (NE) metabolism and pituitary-testicular hormone in male rats. The densities of beta-1 but not beta-2 adrenoreceptors were increased in hypothalamus (anterior and lateral nuclei), thalamus (ventral posterior nucleus) and amygdala (basolateral nucleus) of the STZ diabetic rats. In contrast, a decrease in the rate of metabolism of NE (estimated by the concentration of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol) was observed in these STZ-treated animals. Serum concentrations of luteinizing hormone and testosterone were lower in the STZ diabetic rats. Pretreatment of rats with nicotinamide prevented the induction of hyperglycemia, upregulation of brain beta-1 adrenoreceptors, decreases in NE metabolism and reduction in serum levels of luteinizing hormone and testosterone seen in STZ-treated rats. These data suggest that derangements in the hypothalamic-pituitary-testicular axis seen in uncontrolled diabetes may be secondary to decreases in NE metabolism and compensatory upregulation of beta-1 adrenoreceptors in brain.