Growth hormone directly affects the function of the different lobes of the rat prostate.
In this study, we investigated the involvement of GH in rat prostate function. First, we demonstrated that specific transcripts corresponding to the GH receptor (4.5 kilobases) and to the GH-binding protein (1.2 kilobases) were expressed in the normal rat prostate, but also in all prostatic carcinoma cell lines tested (LNCaP, PC-3, MAT-Lu, MAT-LyLu, and Pif-1). Moreover, these transcripts were much more abundant in the human and rat carcinoma cells than in the normal tissue. One-year-old dwarf rats were supplemented for 7 days with saline (group DR1) or highly purified rat GH (group DR2). Northern blotting and quantitation of prostatic messenger RNAs (mRNAs) revealed that GH increases the steady state levels of transcripts coding for androgen receptor (2.4-fold), type I and II 5 alpha-reductases (2.6- and 2.2-fold), and several androgen-dependent proteins [prostatein C3 subunit (3.6-fold), probasin (11.0-fold), and R. W. B. (Royal Winnipeg Ballet) (12.5-fold)]. This suggests that GH might either potentiate the action of androgens on the prostate or act directly on this gland by a mechanism that does not depend on testicular androgens. To address this question, we supplemented hypophysectomized and castrated adult rats for 7 days with saline (group HC1), rat GH (group HC2), testosterone propionate (group HC3), or GH plus testosterone (group HC4), starting 3 days after castration. In this animal model, the abundance of C3 mRNA increased in all hormone-treated rats; the stimulation factors were 3.5 (group HC2), 25.5 (group HC3), and 9.5 (group HC4) compared to group HC1. Analysis of prostatein synthesis by Western blotting confirmed these results at the protein level. The same trend was observed for probasin and RWB mRNA levels. Probasin mRNA increased 4.5-fold in group HC2 and 12-fold in group HC3, but did not increase in group HC4 (both hormones combined); enhancement of RWB mRNA was, respectively, 5.0-, 28.0-, and 15.0-fold in groups HC2, HC3, and HC4. GH did not affect the abundance of androgen receptor mRNA. As described previously, the level of this mRNA dropped significantly in group HC3. GH alone did not significantly alter the level of either 5 alpha-reductase mRNA, whereas testosterone, alone or with GH, produced a 2-fold increase in type II 5 alpha-reductase mRNA (groups HC3 and HC4). Type I isoenzyme mRNA reached 1.6 times the control level (group HC1) in groups HC3 and HC4.(ABSTRACT TRUNCATED AT 400 WORDS)
Reiter
E
E
Human Biochemistry, Laboratory of Endocrinology, University of Leige, Belgium.
Kecha
O
O
Hennuy
B
B
Lardinois
S
S
Klug
M
M
Bruyninx
M
M
Closset
J
J
Hennen
G
G
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D004392:Dwarfism; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000728:Androgens; D011986:Receptors, Somatotropin; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone