Neuronal signals are required for estrogen-mediated induction of progesterone receptor in cultured rat Schwann cells

Abstract

Rat glial cells from the central nervous system (CNS) and the peripheral nervous system (PNS) express steroid hormone receptors. Whereas progestin receptors (PR) in cultured glial cells of the CNS are estrogen-inducible, similar increase of PR in cultured Schwann cells, the glial cells of the PNS, prepared from newborn rat sciatic nerves, could not be demonstrated. In the present work we have used fetal dorsal root ganglion cultures to study the effect of estrogen and its antagonist ICI 164,384 on the expression of PR in rat Schwann cells. The PR levels were measured by hormone binding in whole cell assays or in cell cytosol, 18 h after excision of the ganglion from the cultures. Treatment of DRG-Schwann cell cultures with estradiol (E2) increased PR levels from about 60 to 160 fmol per mg cytosol protein, in untreated and estrogen-treated cells, respectively. This increase was dose-dependent; maximal induction was obtained at 50 nM E2-concentration. Treatment of the cultures with the antagonist ICI 164,384 completely inhibited the estrogen-induction of PR, whereas ICI alone did not influence receptor levels in Schwann cells. The estrogen-induction of PR was dependent on the presence of dorsal root ganglion during the period of estrogen treatment. Excision of the neuronal mass from the cultures caused a rapid decrease and disappearance of estrogen-inducible progestin receptors, whereas the concentration of non-inducible PR-binding sites remained unchanged. Estradiol had no influence on DRG-Schwann cell proliferation, only replated secondary Schwann cells showed a slightly higher level of proliferation in presence of 100 nM E2 and 5 μM forskolin. Receptors for estrogen (ER) were also demonstrated in DRG-Schwann cells by ligand binding experiments. Specific ER-binding was 36±8 fmol bound estradiol per mg cytosol protein. Finally, both PR and ER were visualized in Schwann cells by indirect immunofluorescence staining using specific anti-receptor antibodies. These findings suggest that the expression of estrogen-inducible progestin receptors in cultured glial cells of the PNS is mediated via intracellular estrogen receptors and that it requires the presence of neuronal signal(s).