Catch-up growth follows an abnormal pattern in experimental renal insufficiency and growth hormone treatment normalizes it

Abstract

The primary goal of this study was to determine if the ability to undergo catch-up growth following a transient injury is preserved in an experimental model of moderate chronic renal failure (CRF) and the effect of growth hormone (GH) administration on such phenomenon. Young rats were subtotally nephrectomized (days 0 and 4) (Nx). From days 11 to 13, food intake was restricted in subgroups of Nx and control (C) rats (NxR and CR). After refeeding, subgroups of NxR and CR rats received GH from days 14 to 20 (NxRGH and CRGH). Rats were killed on days 14 (C, CR, Nx, NxR), 17 and 21 (C, CR, CRGH, Nx, NxR, NxRGH), and 36 (C, CR, Nx, NxR). Longitudinal growth rate was measured by osseous front advance in the proximal tibiae. With refeeding, growth rate of CR, NxR, and NXrGH rats became significantly greater than that of C, indicating catch-up growth. This occurred later and with lower growth rate in NxR than in CR rats, whereas the characteristics of catch-up growth in CR and NxRGH animals were similar. Changes in growth rate were associated with modifications in the morphology and proliferative activity of growth cartilage. We conclude that catch-up growth occurs in renal insufficiency but follows a different pattern from that observed with normal renal function. GH treatment normalizes the pattern of catch-up growth in CRF. Changes in growth velocity are associated to modifications in the structure and dynamics of growth cartilage.

Rapamycin retards growth and causes marked alterations in the growth plate of young rats

“…At sacrifice, blood samples were collected and stored at −20C°until measurement of rapamycin concentrations. Tibiae were removed and the proximal ends fixed and processed for methyl methacrylate embedding, as previously described [13]. Right tibiae were fixed in 40% ethanol for analysis of calcein labeling and BrdU immunohistochemistry.…”

“…Heights of growth cartilage and its hypertrophic zone were identified following morphologic criteria and measured at regular intervals using an image analysis system described elsewhere [13]. Height of the three most distal hypertrophic chondrocytes was measured in alternate columns using the same system.…”

“…Immunodetection of BrdU-labeled cells was carried out as previously described [13]. Briefly, after deplastination and rehydration, frontal 5-μm-thick sections were rinsed in 0.1 M Tris-hydrochloric buffer and treated with trypsin (1 mg/ml, 0.1% CaCl 2 ; 60 min, 37°C).…”

Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment

“…Liver samples and the proximal end of right tibias were immediately frozen in liquid nitrogen for mRNA expression studies. Left tibial proximal ends were embedded in methyl-metacrilate as previously described (2,19). Samples from one-half the animals were fixed in 40% ethanol and used for analysis of calcein and BrdU labeling.…”

“…Snout-to-tail-tip length of rats was measured at death. The longitudinal bone growth rate (m/day) during the 3 days before death was calculated by means of calcein labeling as previously described (2,19).…”