Expression of endothelin receptor subtypes and their messenger RNAs in diabetic rat prostate: effect of insulin treatment.
Streptozotocin (STZ)-induced diabetes causes an upregulation in the expression of endothelin (ET) receptors in the rat prostate (Eur J Pharmacol 310:197, 1996). We examined the effects of insulin treatment, started 8 weeks after the induction of diabetes, on the expression and distribution of ET receptors and their respective mRNAs in the rat prostate. The densities, pharmacological properties and distribution of ET receptors in the rat prostate were examined using radioligand receptor binding and autoradiographic studies, and gene expression of ET receptors was evaluated utilizing the reverse transcription-polymerase chain reaction (RT-PCR). STZ-injected rats had smaller prostates and reduced serum testosterone levels than control and insulin treated diabetic animals. ET receptor density was shown to be significantly higher in the prostate from diabetic rats than those from either control or insulin treated diabetic animals. The pharmacological profile of prostatic ET receptors was similar in all groups (approximately 80% ET(A); 20% ET(B) subtype). ET receptors were predominantly localized to the prostatic stroma. Induction of diabetes increased the expression of mRNA levels of ET(A) and ET receptors, and insulin treatment reversed this upregulation to control levels. These results indicate that (1) ET receptor subtypes are expressed in the rat prostate as transcription and translation products; (2) insulin can normalize the diabetes-induced upregulation in the expression of ET receptors and their respective mRNAs; and (3) diabetes-induced regression of the prostate may involve an alteration in ET receptors.
Saito
M
M
Section of Urology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Wada
Y
Y
Ikeda
K
K
Wang
Z
Z
Foster
H E
HE
Smith
S D
SD
Weiss
R M
RM
Latifpour
J
J
D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D009929:Organ Size; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D015854:Up-Regulation
D001786:Blood Glucose; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007328:Insulin; D007457:Iodine Radioisotopes; D020033:Protein Isoforms; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013739:Testosterone