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1 Center for the Study of Sex Differences, Georgetown University, Washington, DC, USA; Department of Physiology and Biophysics, Georgetown University, Washington, DC, USA
2 #DISTBIMO, University of Genova, Genova, Italy
3 Center for the Study of Sex Differences, Georgetown University, Washington, DC, USA; Department of Medicine, Georgetown University, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: jih{at}georgetown.edu.
Renal injury is greater in male compared to female rats after renal wrap (RW) hypertension. We investigated the role of gonadal steroids in the sex differences
in RW disease severity in male (M) and female (F), castrated (Cast) and ovariectomized (OVX) rats and after dihydrotestosterone (DHT) and 17
-estradiol (E2) treatment. Male castration attenuated the severity of RW-induced glomerulosclerosis (GS) [GS index (GSI): RW-M, 2.1±0.2; RW-Cast, 1.3±0.2; RW-Cast+DHT, 2.4±0.4], mean glomerular volume (MGV) (µm3 x 106: RW-M, 1.9±0.1; RW-Cast, 1.45±0.15; RWCast+
DHT, 1.91±0.15), tubular damage and proteinuria (mg/day: RW-M, 130±8; RWCast, 105±5; RW-Cast+DHT, 142±9) while DHT treatment abrogated these effects. Ovariectomy increased the GSI (RW-F 0.69±0.05; RW-OVX, 1.2±0.1; RW-OVX+E2, 0.65±0.05), tubular damage and MGV (µm3 x 106: RW-F, 1.0±0.06; RW-OVX, 1.5±0.05;
RW-OVX+E2, 0.96±0.06) while E2 treatment prevented these effects. Furthermore, DHT treatment of RW-OVX animals exacerbated the GSI (1.9±0.19), MGV (1.7±0.2 x
106 µm3) and proteinuria (171±21 mg/day) even further. Our data show that the lack of E2 and presence of androgens contribute to progressive renal disease induced by RW hypertension, suggesting that gonadal steroid status is an independent factor in the greater susceptibility men exhibit towards hypertension associated renal disease compared to women.
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