TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) IN PENILE AND PROSTATEGROWTH IN THE RAT DURING SEXUAL-MATURATION

The goal of this study was to determine whether transforming growth fa ctor-beta 1 (TGF-beta 1) may contribute to the arrest of penile growth and the down-regulation of androgen receptors (AR) that occur during sexual maturation in the rat penis. For this purpose, body, penis, and prostate weights were obtained from male rats of increasing ages, and penis and prostate TGF-beta 1 concentrations were determined by a san dwich enzyme-linked immunosorbent assay. The cytosol fraction was obta ined from the shafts and glandes of immature (19-day-old) and adult (9 0-day-old) rat penises, and ARs were measured by a western blot assay. The effect of exogenous TGF-beta 1 on penile growth was examined in v ivo in two groups of immature rats (21 and 27 days old) implanted with miniosmotic pumps delivering either human TGF-beta 1 or vehicle only directly into the corpora cavernosa for 6 days. The penises, prostates , and testes were weighed, and the AR content was estimated by western blot. The growth rate of the penis declined after 8 weeks of age, whe reas the ventral prostate growth rate increased until 14 weeks of age and then slowed down. The content of penile AR protein decreased seven -fold in the adult rats compared to the immature animals. Penile TGF-b eta 1 concentration increased nearly three-fold from the 19-day-old ra ts to a peak at 60 days of age and then decreased over the next 4 mont hs to the initial levels. In contrast, TGF-beta 1 concentration in the prostate was not significantly affected by age and remained below the lowest penile values in all age groups. Transforming growth factor-be ta 1 given locally to the penis reduced penile shaft weight by 38 and 22% in two groups of immature rats, while the weights of the penile gl ans, testis, and ventral prostate remained unaffected. Androgen recept or content was higher in the glans than in the shaft and was not chang ed by TGF-beta 1 treatment. These results suggest that the increase of TGF-beta 1 levels in the penis may reinforce growth arrest caused by the down-regulation of penile ARs, whereas the maintenance of a high c ontent of ARs and a low TGF-beta 1 concentration may allow prostate gr owth to continue.