The estrogen/neurotrophin connection during neural development: is co-localization of estrogen receptors with the neurotrophins and their receptors biologically relevant?

Estrogen enhances neurite growth within the developing rodent forebrain. Estrogen receptor mRNA is co-expressed with the mRNA for the neurotrophins and their receptors. Estrogen may act independently by altering growth-related genes directly, but may interact additionally with growth factors (neurotrophins) and their receptors (trks). Estrogen may also act permissively to facilitate neurotrophin actions by genomic cross-talk with neurotrophin regulatory pathways whose nuclear end points may be the same estrogen-responsive genes. Differential and reciprocal regulation of estrogen and nerve growth factor (NGF) receptor gene expression by their ligands suggests that estrogen and the neurotrophins may influence each other's actions by regulating receptor/ligand availability or by reciprocal regulation at the level of gene transcription or signal transduction. Steroid/neurotrophin interactions may stimulate the synthesis of proteins required for neuronal differentiation, survival and maintenance of function.