REGULATION OF GENE-EXPRESSION BY CORTICOID HORMONES IN THE BRAIN AND SPINAL-CORD

Glucocorticoids (GC) and mineralocorticoids (MC) have profound regulat ory effects upon the central nervous system (CNS). Hormonal regulation affects several molecules essential to CNS function. First, evidences are presented that mRNA expression of the alpha 3 and beta 1-subunits of the Na,K-ATPase are increased by GC and physiological doses of MC in a region-dependent manner. Instead, high IMC doses reduce the BI is oform and enzyme activity in amygdaloid and hypothalamic nuclei, an ef fect which may be related to MC control of salt appetite. The alpha 3- subunit mRNA of the Na,K-ATPase is also stimulated by GC in motoneuron s of the injured spinal cord, suggesting a role for the enzyme in GC n europrotection. Second, we provide evidences for hormonal effects on t he expression of mRNA for the neuropeptide arginine vasopressin (AVP). Our data show that GC inhibition of AVP mRNA levels in the paraventri cular nucleus is sex-hormone dependent. This sexual dimorphism may exp lain sex differences in the hypothalamic-pituitary-adrenal axis functi on between female and male rats. Third, steroid effects on the astrocy te marker glial fibrillary acidic protein (GFAP) points to a complex r egulatory mechanism. In an animal model of neurodegeneration (the Wobb ler mouse) showing pronounced astrogliosis of the spinal cord, in vivo GC treatment down-regulated GFAP immunoreactivity, whereas the membra ne-active steroid antioxidant U-74389F up-regulated this protein. It i s Likely that variations in GFAP protein expression affect spinal cord neurodegeneration in Wobbler mice. Fourth, an interaction between neu rotrophins and GC is shown in the injured rat spinal cord. In this mod el, intensive GC treatment increases immunoreactive low affinity nerve growth factor (NGF) receptor in motoneuron processes. Because GC also increases immunoreactive NGF, this mechanism would support trophism a nd regeneration in damaged tissues. In conclusion, evidences show that some molecules regulated by adrenal steroids in neurons and glial cel ls are not only involved in physiological control, but additionally, m ay play important roles in neuropathology. (C) 1998 Elsevier Science L td. All rights reserved.