Distribution of follistatin messenger ribonucleic acid in the rat brain: Implications for a role in the regulation of central reproductive functions

Follistatin (FS), which binds to the inhibin/activin beta A- or beta B-subunit is localized with and modulates the biological actions of activin in many systems. However, in contrast to the wide distribution of the activin beta-subunit proteins and messenger RNAs (mRNA) in the brain, demonstration of FS mRNA signal has been limited to the olfactory tubercle and layer II of the frontal cortex. We have hypothesized a more extensive distribution of central FS gene expression and localization in regions coinciding with inhibin/activin beta-subunits and possible activin-mediated effects. In the present study, we examined the central distribution of FS mRNA expression in the normal adult male rat;With in situ hybridization analysis, using a P-33-labeled RNA probe specific for rat FS, gene expression is shown to be widely distributed throughout the brain. Abundant FS mRNA. expression is localized in several areas of the olfactory bulb as well as the frontal cortex, a few thalamic nuclei, and in septal regions. Moderate FS mRNA signal is observed in the caudate putamen and various hypothalamic areas including the paraventricular, ventromedial, dorsomedial, and arcuate nuclei. Several brain stem regions are also found to express FS mRNA, including the medial vestibular and solitary tract nuclei. Notably, FS mRNA expression in the medial septal/diagonal band region is localized in patterns that are highly correlative with those of GnRH gene expression and hence may serve to regulate possible activin-mediated effects in these areas. FS mRNA is also expressed in areas associated with the activin-oxytocin pathway (solitary tract nucleus and paraventricular nucleus) and is therefore in a position to modulate the role of activin in the solitary tract nucleus-paraventricular nucleus pathway (afferent system mediating the milk-ejection reflex). The results suggest that FS is centrally localized in sites compatible with a role in the regulation of central reproductive functions.