Regulation of gene expression in rat prostate by androgen and beta-adrenergic receptor pathways.
Denervation of rat ventral prostate has been accomplished by excising prostatic tissue fragments and implanting them under the renal capsules of intact syngeneic rats. This resulted in a substantial reduction of expression of a major organ-specific secretory protein, prostatic binding protein (PBP). The depressed level of PBP and its subunits and mRNAs could be restored, however, to as much as 80% of control levels by the administration of a pharmacological dose of exogenous androgen, testosterone propionate (TP), and/or a beta-adrenergic agonist, isoproterenol (ISO). Furthermore, compared to ascorbate-treated controls, TP and ISO increased the synthesis of total cellular protein and PBP by the prostatic renal implants. TP and/or ISO also remodelled the luminal epithelial structure and elevated secretory functions. ISO alone had no effect, however, in castrated animals, indicating that androgen plays a dominant role in the restoration of tissue PBP content. Concomitant to increased PBP content and remodelling of prostatic histomorphology, androgen was also found to raise the depressed levels of beta 2-adrenergic and androgen receptors in the prostatic isografts maintained in intact hosts. In contrast, although an established rat prostatic epithelial cell line (NbE-1) contains high affinity androgen receptor, androgen failed to restore beta-adrenergic receptor as well as PBP content in this cultured cell line. These results, taken together, suggest that a tight coupling between androgen receptor and beta 2-adrenergic receptor pathways may be a prerequisite for PBP expression and functional differentiation in the rat ventral prostate gland.
Guthrie
P D
PD
Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Freeman
M R
MR
Liao
S T
ST
Chung
L W
LW
D000727:Androgen-Binding Protein / Q000096:biosynthesis / Q000235:genetics*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney; D008297:Male; D011467:Prostate / Q000033:anatomy & histology / Q000378:metabolism* / Q000637:transplantation; D060789:Prostatein; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism; D060765:Secretoglobins; D013739:Testosterone / Q000494:pharmacology; D014598:Uteroglobin; D060788:Mammaglobin B
D000727:Androgen-Binding Protein; D000728:Androgens; D007545:Isoproterenol; D060789:Prostatein; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011944:Receptors, Androgen; D060765:Secretoglobins; D013739:Testosterone; D014598:Uteroglobin; C511484:Scgb1d2 protein, rat; C511483:Scgb1d4 protein, rat; C556468:Scgb2a1 protein, rat; D060788:Mammaglobin B