Expression of aromatase, androgen and estrogen receptors in peripheral target tissues in diabetes.
Our previous studies have shown that diabetes in the male streptozotocin (STZ)-induced diabetic rat is characterized by a decrease in circulating testosterone and concomitant increase in estradiol levels. Interestingly, this increase in estradiol levels persists even after castration, suggesting extra-testicular origins of estradiol in diabetes. The aim of the present study was to examine whether other target organs of diabetes may be sources of estradiol. The study was performed in male Sprague-Dawley non-diabetic (ND), STZ-induced diabetic (D) and STZ-induced diabetic castrated (Dcas) rats (n=8-9/group). 14 weeks of diabetes was associated with decreased testicular (ND, 26.3+/-4.19; D, 18.4+/-1.54; P<0.05), but increased renal (ND, 1.83+/-0.92; D, 7.85+/-1.38; P<0.05) and ocular (D, 23.4+/-3.66; D, 87.1+/-28.1; P<0.05) aromatase activity. This increase in renal (Dcas, 6.30+/-1.25) and ocular (Dcas, 62.7+/-11.9) aromatase activity persisted after castration. The diabetic kidney also had increased levels of tissue estrogen (ND, 0.31+/-0.01; D, 0.51+/-0.11; Dcas, 0.45+/-0.08) as well as estrogen receptor alpha protein expression (ND, 0.63+/-0.09; D, 1.62+/-0.28; Dcas, 1.38+/-0.20). These data suggest that in male STZ-induced diabetic rats, tissues other than the testis may become sources of estradiol. In particular, the diabetic kidney appears to produce estradiol following castration, a state that is associated with a high degree or renal injury. Overall, our data provides evidence for the extra-testicular source of estradiol that in males, through an intracrine mechanism, may contribute to the development and/or progression of end-organ damage associated with diabetes.
Prabhu
Anjali
A
Department of Medicine, Georgetown University Medical Center, 4000 Reservoir Road NW, Washington, DC 20057, United States.
Xu
Qin
Q
Manigrasso
Michaele B
MB
Biswas
Moumita
M
Flynn
Elizabeth
E
Iliescu
Radu
R
Lephart
Edwin D
ED
Maric
Christine
C
D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003920:Diabetes Mellitus / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000097:blood; D008297:Male; D009928:Organ Specificity; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*
D001786:Blood Glucose; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D001141:Aromatase