TISSUE-SPECIFIC REGULATION OF THE GROWTH-HORMONE RECEPTOR GENE IN STREPTOZOCIN-INDUCED DIABETES IN THE RAT

Abnormalities of GH secretion and clearance are well-documented in poo rly controlled insulin-dependent diabetes mellitus (IDDM), but the con tribution of the receptor (GHR) and the GH-binding protein (GHBP) to t hese abnormalities has not been defined. We studied the expression of the GHR/GHBP gene in the livers, hearts and kidneys in streptozocin-in duced diabetes (STZ-D) in the rat. GHR and GHBP mRNA levels were measu red by Northern blot and ribonuclease protection assays. Whereas level s of GHR and GHBP mRNA were significantly decreased in Liver and heart of STZ-D rats when compared with the control group (P<0.01), GHR mRNA was significantly increased in the kidneys of STZ-D rats (P=0.03). Si x days of insulin treatment did not significantly alter the levels of GHR/GHBP mRNA in the liver or heart of STZ-D rats, but significantly d ecreased GHBP mRNA (P=0.04) in the kidney. Circulating IGF-I was reduc ed, as was IGF-I mRNA in the liver and heart of STZ-D rats; only circu lating IGF-I was restored by insulin treatment. Neither STZ-D nor insu lin treatment affected IGF-I or IGF-I receptor mRNA concentrations in the kidney. We conclude that (1) STZ-D modulates the expression of the GHR/GHBP gene and (2) that these changes in GHR/GHBP mRNA concentrati ons are tissue-specific; STZ-D decreases GHR/GHBP mRNA in liver and he art tissue but increases GHR mRNA concentrations in the kidney. Our re sults indicate a role for decreased numbers of hepatic GHRs in the pat hogenesis of resistance to GH's actions in terms of IGF-I generation a nd promotion of linear growth in IDDM. We postulate that increased GHR expression in the kidney may be involved in the renal complications o f IDDM.