Early hyperplastic renal growth after uninephrectomy in adult female rats

Abstract

The early, accelerated remnant kidney growth following uninephrectomy (UNX) occurs through alternate mechanisms in juvenile and adult male rats, which may govern the type of renal growth that occurs after UNX. Early compensatory renal growth (CRG) in the adult male rat is GH dependent, but independent of changes in the renal insulin-like growth factor I (IGF-I) system. In contrast, CRG is GH independent in the juvenile male rat, but is associated with significant increases in the renal IGF-I system, and hyperplastic kidney growth. The few studies that examined early CRG in female animals suggest that remnant kidney growth is less than that observed in males, and there is a hyperplastic component, indicating potential gender differences. Whether these differences result from alternate growth mechanisms is unknown. The purpose ofthe present study was to determine the rate, type, and potential mechanism of early remnant kidney growth in adult female rats after UNX. GH levels were determined in conscious, sham-operated, and UNX adult female Wistar rats 24 h postsurgery. Unlike previous findings in adult male UNX rats, pulsatile GH levels were not elevated in UNX female rats. When GH release was suppressed using an antagonist to GH-releasing factor, remnant kidney growth was not different from that in saline/UNX remnant kidneys (25.7+/-4.8% vs. 27.7+/-2.1%, respectively, at 48 h post-UNX). This GH-independent CRG was associated with significant hyperplastic growth in both adult andjuvenile female remnant kidneys, as determined by bromodeoxyuridine incorporation and increases in total DNA. Also associated with the mitogenic growth in the adult female were significant 2- to 4-fold increases in remnant kidney IGF-I receptor gene expression, which occurred in the presence and absence of pulsatile GH secretion. Lastly, the growth rate of adult female remnant kidneys was not different from that observed in male remnant kidneys at these early time points (0.21+/-0.02 vs. 0.20+/-0.02 g at 24 h, and 0.26+/-0.02 vs. 0.30+/-0.03 g at 48 h in female and male remnant kidneys, respectively; P = NS). Thus, in female rats, the initial phase of CRG is GH independent, but is associated with significant increases in remnant kidney IGF-I receptor gene expression and hyperplastic renal growth. This, in addition to previous findings, indicates that there are sex differences in early CRG after UNX. Moreover, the findings confirm that the mechanism governing the initial phase of CRG appears to be a critical determinant for significant hyperplastic remnant kidney growth.