Prostatic luminal cell differentiation and prostatic steroid-binding protein (PBP) gene expression are differentially affected by neonatal castration

BACKGROUND. Although normal prostatic development is androgen-dependent, th e prostate continues to grow in the neonate despite castration. However, th e manner in which neonatal growth of the prostate occurs, in the absence of the testis, remains largely unknown. The purpose of this study was to exam ine the differentiation of prostatic epithelial cells after neonatal castra tion. METHODS. Immunohistochemistry was utilized to detect the expression of diff erentiation products: basal-cell cytokeratin (CK 5), luminal-cell cytokerat in (CK 18), and prostatic steroid-binding protein (PBP), a ventral prostate -specific marker indicative of secretory function in luminal cells. The rev erse transcription-polymerase chain reaction was used to detect transcripti on products of the three polypeptide subunits of PBP, designated C1, C2, an d C3. Rats were castrated on day 5 after birth, and ventral prostates were collected on day 14. Dihydrotestosterone was injected (100 mu g/animal ever y 2 days) in castrated animals to determine if PBP expression could be init iated by androgen. RESULTS. Although no major effects of castration were detected on the diffe rentiation of stromal or basal cells (which differentiate prior to day 5), castration had a pronounced effect on luminal-cell differentiation. Castrat ion inhibited PBP protein expression, but did not affect the expression of luminal-cell cytokeratin (CK 18) protein. Furthermore, castration reduced C 1, C2, and C3 transcription. Androgen replacement to castrated animals allo wed for the initiation of PBP expression, although its onset was delayed. CONCLUSIONS. These observations indicate that the testis is not necessary f or prostatic luminal-cell differentiation, but is necessary for full expres sion of luminal-cell secretory phenotype. Furthermore, our study suggests t hat factors of testicular origin, in addition to androgen, are needed for p roper timing of PBP expression. This investigation establishes that the cyt ological and the physiological differentiation of the rat prostate are diff erentially regulated. Prostate 43:195-204, 2000. (C) 2000 Wiley-Liss, Inc.