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 f unction. First, we demonstrated that specific transcripts correspondin g 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 al l prostatic carcinoma cell lines tested (LNCaP, PC-3, MAT-Lu, MAT-LyLu , and Pif-1). Moreover, these transcripts were much more abundant in t he human and rat carcinoma cells than in the normal tissue. One-year-o ld 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 st eady state levels of transcripts coding for androgen receptor (2.4-fol d), type I and II 5 alpha-reductases (2.6- and 2.2-fold), and several androgen-dependent proteins [prostatein C3 subunit (3.6-fold), probasi n (11.0-fold), and R.W.B. (Royal Winnipeg Ballet) (12.5-fold)]. This s uggests that GH might either potentiate the action of androgens on the prostate or act directly on this gland by a mechanism that does not d epend on testicular androgens. To address this question, we supplement ed hypophysectomized and castrated adult rats for 7 days with saline ( group HC1), rat GH (group HC2), testosterone propionate (group HC3), o r GH plus testosterone (group HC4), starting 3 days after castration. In this animal model, the abundance of C3 mRNA increased in all hormon e-treated rats; the stimulation factors were 3.5 (group HC2), 25.5 (gr oup HC3), and 9.5 (group HC4) compared to group HC1. Analysis of prost atein synthesis by Western blotting confirmed these results at the pro tein level. The same trend was observed for probasin and RWB mRNA leve ls. 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); enha ncement of RWB mRNA was, respectively, 5.0-, 28.0-, and 15.0-fold in g roups HC2, HC3, and HC4. GH did not affect the abundance of androgen r eceptor mRNA. As described previously, the level of this mRNA dropped significantly in group HC3. GH alone did not significantly alter the l evel of either 5 alpha-reductase mRNA, whereas testesterone, 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 cont rol level (group HC1) in groups HC3 and HC4. In addition, we demonstra ted, using a nuclear run-on assay, that GH significantly enhances the transcription rate of the C3 and probasin genes. Moreover, both insuli n-like growth factor I and testesterone stimulate transcription of the C3 gene in the rat prostate. We conclude that GH is involved in regul ating prostate function. It could either act directly on the prostate (via its specific receptor) or indirectly, via systemic insulin-like g rowth factor I produced in the liver under GH control. The effects of GH concern all lobes of the organ and are at least in part androgen in dependent. The observed increases in the levels of various prostate-sp ecific marker mRNAs are due at least partly to transcriptional activat ion.