Interaction of testosterone with inhibin alpha and betaA subunits to regulate prostate gland growth

Testosterone regulation of prostate gland growth has been shown to involve reciprocal interaction with inhibin and activin. This study was therefore conducted to correlate the effect of testosterone on prostate gland proliferation and differentiation with the level of expression of inhibin alpha and betaA subunits. Immature dogs were treated with testosterone for 0, 3, 7, and 14 days and prostate gland growth was assessed by morphological and immunohistological localization of differentiation and proliferation markers. The results showed that testosterone treatment resulted in an initial significant increase in PCNA proliferation index by days 3 and 7, followed by a significant decrease by day 14 post-treatment. Interestingly, the decrease of cell proliferation was associated with structural and biochemical changes characteristic of glandular and stromal differentiation of the prostate gland. These changes include progressive glandular ductal canalization and inter-ductal stroma differentiation which were apparent from a gradual shift from vimentin expression to vimentin and alpha-actin expression. Testosterone also had a differential effect on inhibin alpha and beta subunits. Although testosterone treatment resulted in significant and constant inhibition of alpha subunit mRNA expression, it resulted in a significant increase of betaA mRNA expression by day 3, followed by a decrease by days 7 and 14. These results indicated that testosterone acts first to drive proliferation of undifferentiated prostatic cells and then to maintain a low proliferation turnover of differentiated cells. Because it has been shown that activin is an antagonistic regulator of androgens, the attenuated stimulatory effect of testosterone on cell proliferation by day 14 might be mediated, at least in part, by interplay between testosterone and activin.