BACKGROUND: Male gender is a risk factor for progression of @entity8 ( @entity8 ), clinically and in the Han:SPRD @entity35 model. Orchiectomy limits progression, but mechanisms of the detrimental effect of @entity342 , and/or beneficial effects of @entity172 , are not known. This protocol tested the hypothesis that male gender (intact @entity342 status) promotes progression, while female gender (intact @entity172 status) is protective; and that these disease-modifying effects are due to changes in expression of known fibrotic mediators. METHODS: Studies were performed in male and female noncystic control (+/+) and cystic (+/-) @entity35 subjected to orchiectomy, ovariectomy, or sham operation. At 12 weeks of age, renal function was measured. Blood and kidneys were taken for measurement of plasma and renal @entity3449 , endothelin ( @entity1827 ), endothelial @entity842 synthase (eNOS), and @entity6667 ( @entity6667 ), using biochemical, protein expression, and immunohistochemical methods. RESULTS: Cystic male @entity35 exhibited significantly reduced glomerular filtration (GFR) and effective renal plasma flow (ERPF) rates, with suppression of plasma and renal @entity3449 , up-regulation of renal @entity1827 and eNOS, and down-regulation of renal @entity6667 expression. Orchiectomy attenuated the fall in GFR and ERPF, while numerically limiting changes in eNOS and @entity6667 . Female @entity35 exhibited less cystic growth, with normal @entity3449 status, lesser elevation of renal @entity1827 , and proportionately lesser changes in @entity6667 and eNOS. Ovariectomy led to higher blood pressure and reduced GFR and ERPF, with a trend toward upregulation of @entity1827 , and significant down-regulation of @entity6667 and eNOS. CONCLUSION: Female gender is protective, but ovariectomy attenuates the protective effect of female gender, in association with changes in renal expression of @entity1827 , @entity6667 , and eNOS. The accelerated disease in male @entity35 can be attenuated by orchiectomy and consequent changes in expression of disease mediators.

Gender hormones and the progression of experimental XXXX .

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen'] @entity8 :: ('MESH:D007674', 'Disease') :: ['autosomal-dominant polycystic kidney disease', 'ADPKD'] @entity3449 :: ('24715(Tax:10116)', 'Gene') :: ['renin'] @entity1827 :: ('24323(Tax:10116)', 'Gene') :: ['ET-1'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity6667 :: ('83785(Tax:10116)', 'Gene') :: ['vascular endothelial growth factor', 'VEGF']
@entity8 :: (MESH:D007674,Disease) :: ['polycystic kidney disease']
