ADRENAL-STEROID REGULATION OF NEUROTROPHIC FACTOR EXPRESSION IN THE RAT HIPPOCAMPUS

Adrenal steroids and neurotrophic factors are important modulators of neuronal plasticity, function, and survival in the rat hippocampus. Ad renal steroids act through two receptor subtypes, the glucocorticoid r eceptor (GR) and the mineralocorticoid receptor, and activation of eac h receptor subtype has distinct biochemical and physiological conseque nces. Adrenal steroids may exert their effects on neuronal structure a nd function through the regulation of expression of neurotrophic and g rowth-associated factors. We have examined adrenal steroid regulation of the neurotrophins brain-derived neurotrophic factor, neurotrophin-3 , and basic fibroblast growth factor, as well as the growth associated protein GAP-43, through activation of GR or mineralocorticoid recepto r with selective agonists. Our findings indicated that in CA2 pyramida l cells, adrenalectomy resulted in decreases in the levels of basic fi broblast growth factor and neurotrophin-3 messenger RNA, which were pr evented by activation of mineralocorticoid but not glucocorticoid rece ptors. Adrenalectomy-induced increases in GAP-43 and brain-derived neu rotrophic factor messenger RNA levels could be blocked by activation o f glucocorticoid receptors in CA1, but not in CA3, pyramidal cells. Th us the extent to which adrenal steroids regulate hippocampal neurotrop hic and growth-associated factors, appears to be dependent both on the adrenal steroid receptor subtype activated and on the hippocampal sub region examined.