The effect of castration on endothelins, their receptors and endothelin converting enzyme in rat prostate.
We previously have shown that experimental diabetes in rats causes prostatic involution, reduces serum testosterone levels, and causes an upregulation in prostatic endothelin (ET) receptors. Furthermore, insulin treatment normalizes these changes (Saito et al., Mol Cell Biochem 210:1-12, 2000). Since experimental diabetes-induced reduction in serum testosterone may be a factor in the alteration of the ET receptors and of prostatic growth, we investigated the effect of castration, another means of involuting the prostate and decreasing serum testosterone levels, on the expression of ET receptors in ventral and dorsolateral regions of the rat prostate.Three-month-old Sprague-Dawley rats were surgically castrated or sham operated, and then killed on the 7th post-operative day. Biochemical and pharmacological properties, and localization of ET receptors in the rat prostate, were determined by performing a series of binding experiments with [(125)I]ET-1 and by light microscopy autoradiography, respectively. The expression levels of ET-1, ET-3, ET receptor subtypes and endothelin converting enzyme-1 (ECE-1) mRNAs were assessed by relative multiplex reverse transcription polymerase chain reaction (RT-PCR). The total density of ET receptors increases 3.7-fold in the ventral and 2.1-fold in the dorsolateral regions of the castrated rat prostate compared to sham operated animals. Castration causes a 2.4-fold increase in the density of alpha(1)-adrenoceptors (alpha(1)-ARs) in the ventral region of the prostate, but no change in the density of alpha(1)-ARs in the dorsolateral region of the rat prostate. The predominant ET receptor subtype in the rat prostate is the ETA subtype, which is mainly located in the prostatic stroma. In addition, RT-PCR data show an upregulation in the expression of ETB receptor subtype, ET-1 and ECE-1 mRNA in both regions, and a downregulation in the expression of ETA receptor subtype mRNA in the dorsolateral region of the castrated rat prostate. There is no change in the expression of ET-3 mRNA in either region. Castration does not cause significant changes in the pharmacological properties of prostatic ET receptors, i.e., the predominance of ETA receptors in either region of the prostate, or the expression of ETA receptor subtype mRNA in the ventral region of the castrated rat prostate. These results suggest the existence of a region/lobe-specific regulatory role for testosterone in the expression of the ET receptor system in the rat prostate.
Section of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
Wataru
W
Takahashi
Parviz
P
Afiatpour
Harris E
HE
Jr  Foster
Kazuyoshi
K
Ikeda
Yoshihiro
Y
Wada
Robert M
RM
Weiss
Jamshid
J
Latifpour
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001345:Autoradiography; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D019334:Endothelin-3 / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D015870:Gene Expression; D008297:Male; D008666:Metalloendopeptidases; D008853:Microscopy / Q000379:methods; D009919:Orchiectomy; D009929:Organ Size; D011467:Prostate / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D019332:Endothelin-1; D019334:Endothelin-3; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes