Sex hormones and gender-related differences: their influence on chronic renal allograft rejection.
BACKGROUND
Renal hemodynamics and immune responses differ between males and females. Thus, sex hormones and genetically determined gender differences may determine the process of chronic rejection to some extent.


METHODS
Female (F) or male (M) F344 kidneys were orthotopically transplanted into ovariectomized female Lewis recipients and were treated for 16 weeks with either estradiol, testosterone, or vehicle.


RESULTS
Testosterone treatment resulted in increased urinary protein excretion independently of the donor gender, as well as extended glomerular sclerosis, interstitial fibrosis, and severe vascular lesions. Additionally, mononuclear cell infiltration was most pronounced in these animals, in parallel to an increased expression of intercellular adhesion molecule-1 (ICAM-1), fibronectin, laminin, and transforming growth factor-beta (TGF-beta) in the grafts. Estradiol treatment resulted in an improved graft function, reduced glomerular sclerosis, and a diminished cellular infiltration, in parallel to a reduced ICAM-1, fibronectin, laminin, and TGF-beta expression. In animals treated with vehicle, the gender of the donor influenced the outcome. Grafts of male origin had good graft function and histology, whereas grafts from female donors developed severe proteinuria and glomerular, interstitial, and vascular damage.


CONCLUSIONS
These results suggest that a protective effect of estradiol on the progression of chronic rejection exists that is independent of donor gender. Additionally, a male kidney may benefit from the absence of testosterone, whereas the function of a female kidney deteriorates in the absence of estradiol.
Müller
V
V
Department of Nephrology, University Hospital, Essen, Germany.
Szabó
A
A
Viklicky
O
O
Gaul
I
I
Pörtl
S
S
Philipp
T
T
Heemann
U W
UW
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D002908:Chronic Disease; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006084:Graft Rejection / Q000188:drug therapy*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D016030:Kidney Transplantation; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D016212:Transforming Growth Factor beta; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I