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

Prepubertal onset of diabetes mellitus (DM) in male rats delays diabetic renal hypertrophy and suppresses renal transforming growth factor-beta (TGF-beta) 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 approximately 35%, total renal TGF-beta approximately 35%, and mRNA for TGF-beta inducible gene H3 (betaIG-H3) approximately 200%. TGF-beta levels did not increase with DM in prepubertal animals, but renal weight increased approximately 40%, similar to the enlargement seen in adults. In nondiabetic rats, ovariectomy suppressed renal TGF-beta levels by 25-50% in both age groups, but betaIG-H3 was stable in younger animals and increased by approximately 200% in older animals after ovariectomy. Ovariectomy increased kidney weight approximately 10% in both age groups. DM further increased kidney weight by an additional 40% after ovariectomy with an approximately 150% increase in betaIG-H3, even though TGF-beta levels were not significantly increased. Prepubertal (approximately 99% lower), diabetic (approximately 50% lower), and ovariectomized rats (approximately 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-beta 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 betaIG-H3 is dissociated from TGF-beta under these conditions. These observations may help explain some of the sex differences demonstrated in progressive kidney diseases, including DM.