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Dissociation of renal TGF- and hypertrophy in female rats with diabetes mellitus

Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska 68198-2169

Submitted 2 February 2004 ; accepted in final form 21 July 2004

Prepubertal onset of diabetes mellitus (DM) in male rats delays diabetic renal hypertrophy and suppresses renal transforming growth factor- (TGF-) compared with onset in adults. Because there are sex differences in normal and pathological renal growth, we performed similar experiments in female rats and examined the effects of prior ovariectomy. As in male rats, adult onset of DM increased renal weight 35%, total renal TGF- 35%, and mRNA for TGF- inducible gene H3 (IG-H3) 200%. TGF- levels did not increase with DM in prepubertal animals, but renal weight increased 40%, similar to the enlargement seen in adults. In nondiabetic rats, ovariectomy suppressed renal TGF- levels by 25–50% in both age groups, but IG-H3 was stable in younger animals and increased by 200% in older animals after ovariectomy. Ovariectomy increased kidney weight 10% in both age groups. DM further increased kidney weight by an additional 40% after ovariectomy with an 150% increase in IG-H3, even though TGF- levels were not significantly increased. Prepubertal (99% lower), diabetic (50% lower), and ovariectomized rats (90% lower) all tended toward lower estradiol levels than intact adults, although not all differences were statistically significant. Both prepubertal onset and ovariectomy suppress TGF- in the kidneys of female rats with DM compared with adult-onset animals, but these states have no effect on renal enlargement. Production of the extracellular matrix component IG-H3 is dissociated from TGF- under these conditions. These observations may help explain some of the sex differences demonstrated in progressive kidney diseases, including DM.

ovarectomy; estrogen; transforming growth factor--inducible gene H3

This article has been cited by other articles:

				J. Sun, K. Devish, W. J. Langer, P. K. Carmines, and P. H. Lane Testosterone treatment promotes tubular damage in experimental diabetes in prepubertal rats Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1681 - F1690. [Abstract] [Full Text] [PDF]