RECIPROCAL REGULATION OF ESTROGEN AND NGF RECEPTORS BY THEIR LIGANDS IN PC12 CELLS

Recent work has shown that estrogen receptor mRNA and protein co-local ize with neurotrophin receptor systems in the developing basal forebra in. In the present study we examined the potential for reciprocal regu lation of estrogen and neurotrophin receptor systems by their ligands in a prototypical neurotrophin target, the PC12 cell. Using in situ hy bridization histochemistry, RT-PCR and a modified nuclear exchange ass ay, we found both estrogen receptor mRNA and estrogen binding in PC12 cells. Moreover, while estrogen binding was relatively low in naive PC 12 cells, long-term exposure to NGF enhanced estrogen binding in these cells by sixfold. Furthermore, concurrent exposure to estrogen and NG F differentially regulated the expression of the two NGF receptor mRNA s. The expression of trkA mRNA was up-regulated, while p75(NGFR) mRNA was down-regulated transiently. The present data indicate that NGF may increase neuronal sensitivity to estrogen, and that estrogen, by diff erentially regulating p75(NGFR) and trkA mRNA, may alter the ratio of the two NGF receptors, and, consequently, neurotrophin responsivity. I n view of the widespread co-localization of estrogen and neurotrophin receptor systems in the developing CNS, the reciprocal regulation of t hese receptor systems by NGF and estrogen may have important implicati ons for processes governing neural maturation and the maintainance of neural function. (C) 1993 John Wiley & Sons, Inc.