Adrenal Steroid Regulation of Neurotrophic Factor Expression in the Rat Hippocampus

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Abstract
Adrenal steroids and neurotrophic factors are important modula- tors of neuronal plasticity, function, and survival in the rat hippocam- pus. Adrenal steroids act through two receptor subtypes, the glu- cocorticoid receptor (GR) and the mineralocorticoid receptor, and activation of each receptor subtype has distinct biochemical and phys- iological consequences. Adrenal steroids may exert their effects on neuronal structure and function through the regulation of expression of neurotrophic and growth-associated factors. We have examined adrenal steroid regulation of the neurotrophins brain-derived neu- rotrophic factor, neurotrophin-3, and basic fibroblast growth factor, as well as the growth associated protein GAP-43, through activation of GR or mineralocorticoid receptor with selective agonists. Our findings indicated that in CA2 pyramidal cells, adrenalectomy resulted in decreases in the levels of basic fibroblast growth factor and neuro- trophin-3 messenger RNA, which were prevented by activation of mineralocorticoid but not glucocorticoid receptors. Adrenalectomy- induced increases in GAP-43 and brain-derived neurotrophic factor messenger RNA levels could be blocked by activation of glucocorticoid receptors in CA1, but not in CA3, pyramidal cells. Thus the extent to which adrenal steroids regulate hippocampal neurotrophic and growth-associated factors, appears to be dependent both on the ad- renal steroid receptor subtype activated and on the hippocampal subregion examined. (Endocrinology 139: 3112-3118, 1998)

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