Transforming growth factor beta 1 transduced mouse prostate reconstitutions: I. Induction of neuronal phenotypes

We previously showed that retroviral transduction of transforming growth factor beta 1 (TGF-beta 1) induces focally hyperplastic lesions resembling benign prostatic hyperplasia (BPH) and an increase in the number of ganglion-like cells in the mouse prostate reconstitution (MPR) model in vivo. In the present study we further characterize the neuronal phenotypes induced by TGF-beta 1 retroviral transduction in MPRs.

Computer-assisted morphometric analysis was used to evaluate neuronal density. Neuronal cell markers, including neurofilament, neuron-specific enolase, tyrosine hydroxylase, choline acetyltransferase, L-met enkaphaline, and serotonin, were detected by immunostaining.

A fourfold increase in neuronal density was observed in TGF-beta 1 retrovirus-transduced MPRs. The relative frequencies of neuronal subtypes remained similar, with catecholaminergic and cholinergic neurons presenting as the most abundant. We found no evidence of infection of neurons; therefore, increased neuronal density was likely due to paracrine activities.

Our results suggest that enforced TGF-beta 1 expression leads to growth and/or survival of both catecholaminergic and cholinergic neuronal cells in mouse prostate reconstitutions.