Steroid hormone receptors and steroid action in rat glial cells of the central and peripheral nervous system

Abstract

The nervous system is a target for sex steroid hormones which have profound actions on the growth, maturation, differentiation and functioning of brain cells. We found that some steroids, termed "neurosteroids", are synthesized within the brain by glial cells. The term "neurosteroids" designates their site of synthesis--the nervous system, either de novo from cholesterol or from steroid hormone precursors. The biological effects of steroid hormones are mediated by specific high-affinity intracellular receptors, which, after hormone binding, function as activated transcription factors. The presence of such receptors was shown in primary cultures of oligodendrocytes and astrocytes, derived from forebrains (CNS), and in Schwann cells, derived from sciatic nerves (PNS), of newborn rats. In glial cells of the CNS, progesterone-, glucocorticoid-, estrogen and androgen-receptors (PR, GR, ER, AR) were demonstrated and of these receptors, only PR was estrogen-inducible. In glial cells of the PNS, the presence of PR and ER was shown, but the PR in Schwann cell cultures was not inducible by estrogen treatment. Different effects of steroids on glial cell growth and differentiation during primary culture were observed. In particular, a striking increase of myelin-specific proteins such as myelin basic protein (MBP) and cyclic nucleotide phosphodiesterase (CNPase) was observed when oligodendrocytes, the myelinating glial cells of the CNS, were cultured in the presence of progesterone, as determined by indirect immunofluorescence staining and immunoblotting. Insulin also increases MBP and CNP-ase in oligodendrocytes and the combined treatment (insulin + progesterone) promotes a strong synergistic stimulation (14-fold increase) of myelin protein expression. Estradiol also increases MBP- and CNPase expression in oligodendrocytes, although to a lesser extent than progesterone. In the search for optimal stimulation of myelin-protein expression, several progesterone analogues were tested and the results are discussed.