Effects of Exogenous IGF-I on Endogenous IGF-I Production, Function and Hyperplasia/Hypertrophy of Kidney during Compensatory Renal Growth in Hypophysectomized Rats

Han, Sang Won; Cho, Chul Kyu; Choi, Seung Kang

Abstract

PURPOSE: Compensatory renal hypertrophy(CRH) after loss of considerable renal volume is essential process for recovery and maintenance of renal function, but on the other hand CRH induces glomerulosclerosis, eventually renal failure. Recently, the considerable studies reveal that insulin-like growth factor-I(IGF-I) is an important molecule relating to renal hypertrophy. This study investigates the possibility of IGF-I as a therapeutic agent, it should be proved whether external IGF-I affects renal function and glomerulosclerosis or does not affect in devoid state of growth hormone(GH) effect.
MATERIALS AND METHODS
100?150g Sprague-Dawley male rats were hypophysectomized by transpharyngeal approach and hypophysectomy were confirmed by daily monitoring of body weight for 3weeks. The left kidney were removed in the rats of UNX group(uninephrectomy) and UNX+IGF-I group(IGF-I treated after uninephrectomy), and sham operation were done in the other rats of control group and IGF-I group(IGF-I treated). Recombinant IGF-I were administered via Alzet osmotic minipump for 5 days in rats of IGF-I group and UNX+IGF-I group. At the 5th day after uninephrectomy, the glomerular filtration rate(GFR) and the effective renal plasma flow(ERPF) were investigated by measuring recovery of 99mTc-DTPA and 125I-hippurate, and then the rats were sacrificed and the kidneys were removed. The wet kidney weights were measured in removed kidneys, renal IGF-I concentrations were measured by RIA, and cellular proliferation were evaluated by flow-cytometry.
RESULTS
1. The wet kidney weight per body weight significantly increased after uninephrectomy, and had not been affected by IGF-I treatment regardless of uninephrectomy. 2. Renal IGF-I tended to increase after uninephrecromy, and significantly increased with IGF-I treatment in both IGF-I and UNX+IGF-I. The level of renal IGF-I of UNX+IGF-I group was significantly higher than that of IGF-I group. 3. Total GFR tended to decreased after uninephrectomy and were significantly increased by IGF-I treatment regardless of uninephrectomy. 4. The GFR per g wet kidney weight significantly increased after uninephrectomy, and were significantly increased by IGF-I treatment regardless of uninephrectomy. 5. Total ERPF were not significantly changed after uninephrectomy and significantly increased by IGF-I treatment in sham operation group but did not changed by IGF-I treatment in uninephrectomy group. 6. The ERPF per g wet weight significantly increased after uninephrectomy, and significantly increased by IGF-I treatment in sham operation group but did not changed by IGF-I treatment in uninephrectomy group. 7. The mean % of S1 phase cells were 33.6% in UNX+IGF-I group, 23.5% in IGF-I group, 19.96% in UNX group, and 10.4% in control group. The mean % of G2+M phase cells were 2.5% in UNX+IGF-I group, 1.95% in IGF-I group, 1.73% in UNX group, and 1.2% in control group.
CONCLUSIONS
GH non-dependent IGF-I participate in CRH, and only IGF-I without GH increases renal function. IGF-I treatment during CRH might increase GFR by changing glomerular efferent arteriol of filtration fraction.