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, the prostate continues to grow in the neonate despite castration. However, the 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 examine the differentiation of prostatic epithelial cells after neonatal castration.


METHODS
Immunohistochemistry was utilized to detect the expression of differentiation products: basal-cell cytokeratin (CK 5), luminal-cell cytokeratin (CK 18), and prostatic steroid-binding protein (PBP), a ventral prostate-specific marker indicative of secretory function in luminal cells. The reverse transcription-polymerase chain reaction was used to detect transcription products of the three polypeptide subunits of PBP, designated C1, C2, and C3. Rats were castrated on day 5 after birth, and ventral prostates were collected on day 14. Dihydrotestosterone was injected (100 microg/animal every 2 days) in castrated animals to determine if PBP expression could be initiated by androgen.


RESULTS
Although no major effects of castration were detected on the differentiation of stromal or basal cells (which differentiate prior to day 5), castration had a pronounced effect on luminal-cell differentiation. Castration inhibited PBP protein expression, but did not affect the expression of luminal-cell cytokeratin (CK 18) protein. Furthermore, castration reduced C1, C2, and C3 transcription. Androgen replacement to castrated animals allowed for the initiation of PBP expression, although its onset was delayed.


CONCLUSIONS
These observations indicate that the testis is not necessary for prostatic luminal-cell differentiation, but is necessary for full expression of luminal-cell secretory phenotype. Furthermore, our study suggests that factors of testicular origin, in addition to androgen, are needed for proper timing of PBP expression. This investigation establishes that the cytological and the physiological differentiation of the rat prostate are differentially regulated.
Janulis
L
L
Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA. l-janulis@nwu.edu
Nemeth
J A
JA
Yang
T
T
Lang
S
S
Lee
C
C
D000727:Androgen-Binding Protein / Q000096:biosynthesis / Q000235:genetics*; D000728:Androgens / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D003172:Complement C1 / Q000096:biosynthesis / Q000235:genetics; D003175:Complement C2 / Q000096:biosynthesis / Q000235:genetics; D003176:Complement C3 / Q000096:biosynthesis / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D007633:Keratins / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D049488:Phosphatidylethanolamine Binding Protein; D011467:Prostate / Q000166:cytology*; D060789:Prostatein; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060765:Secretoglobins; D014598:Uteroglobin; D060788:Mammaglobin B
D000727:Androgen-Binding Protein; D000728:Androgens; D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D013196:Dihydrotestosterone; D007633:Keratins; D049488:Phosphatidylethanolamine Binding Protein; D060789:Prostatein; D012333:RNA, Messenger; D060765:Secretoglobins; D014598:Uteroglobin; C511482:PEBP1 protein, human; C511484:Scgb1d2 protein, rat; C511483:Scgb1d4 protein, rat; C556468:Scgb2a1 protein, rat; D060788:Mammaglobin B