Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor-I using an antiserum to rat growth hormone

1989 ◽  
Vol 122 (1) ◽  
pp. 79-86 ◽  
Author(s):  
D. J. Flint ◽  
M. J. Gardner

ABSTRACT Treatment of rats for 24 h on day 2, 10 or 20 of age with a specific antiserum to rGH (anti-(rGH)), GH, bromocriptine (CB-154) or prolactin failed to influence body weight gain or serum concentrations of insulin-like growth factor-I (IGF-I). On day 28 of age, however, anti-(rGH) completely inhibited body weight gain and markedly reduced circulating IGF-I concentrations, effects which were completely prevented by exogenous ovine GH (oGH). When administered to control rats on day 28 oGH caused supranormal weight gain and serum IGF-I concentrations. These results suggested that GH does not play a significant role in growth or regulation of serum IGF-I until after day 20 of age. By contrast, when anti-(rGH) was given for 4 consecutive days beginning on day 2 of life, body weight gain was reduced within 48 h and remained so until at least 28 days of age. Tail length was also significantly reduced. The effect was due to inhibition of GH effects since serum GH concentrations were low and exogenous GH prevented the effect. Inhibition of growth during the first 14 days of life occurred in the absence of any effect on serum IGF-I although by 21 days of age serum IGF-I was considerably lower than in control rats. The prolonged reduction in growth after treatment has stopped appeared to be due to a cytotoxic effect on the pituitary gland since pituitary weight and GH but not prolactin content were significantly decreased. The data are consistent with the hypothesis that in the neonate GH may be processed in serum so that a proportion of it is not recognized by an antiserum to pituitary GH. It would appear that inhibition of GH secretion reduces growth rate by at least 30–40% up to 14 days of age, 50% by 21 days of age and completely by 28 days. Effects of GH on growth could not be fully explained by regulation of serum IGF-I concentrations. Journal of Endocrinology (1989) 122, 79–86

1990 ◽  
Vol 124 (3) ◽  
pp. 381-386 ◽  
Author(s):  
M. J. Gardner ◽  
D. J. Flint

ABSTRACT Treatment of neonatal rats on days 2–5 with antibodies against rat GH (rGH) markedly reduced body weight gain and serum concentrations of insulin-like growth factor-I for 6–8 weeks in both females and males, after which weight gain normalized without evidence of catch-up growth. There were no significant effects on serum prolactin, tri-iodothyronine or corticosterone. Testis and ovarian weights were reduced, although only in proportion to body size. In females, but not males, the treated rats, though lighter, had increased fat deposition in the parametrial depot. Pituitary weight was considerably reduced over 100 days later, as was the pituitary content of GH, but not prolactin. The response to GH-releasing factor of both male and female rats was also greatly reduced at this time. Taken together with the fact that these rGH antibodies can bind directly to somatotrophs, we propose that the long-term effects of the antibodies are induced by specific somatotroph destruction. Journal of Endocrinology (1990) 124, 381–386


1991 ◽  
Vol 128 (1) ◽  
pp. 97-105 ◽  
Author(s):  
F. M. Tomas ◽  
S. E. Knowles ◽  
P. C. Owens ◽  
L. C. Read ◽  
C. S. Chandler ◽  
...  

ABSTRACT The ability of insulin-like growth factor-I (IGF-I) to protect against losses of body protein during periods of dietary nitrogen restriction has been evaluated in young rats. Recombinant human IGF-I was administered by osmotic pumps at dose rates of 0, 1·2 or 2·9 mg/kg per day over a 7-day period beginning with the transfer of animals from an 18% to a 4% protein diet. A fourth group received the potent truncated IGF-I analogue, des(1–3)IGF-I, at a dose of 1·2 mg/kg per day over a comparable 7-day period. Plasma IGF-I levels were reduced by 60% following nitrogen restriction, a reduction that was partly prevented by IGF-I administration, especially at the higher dose, but not measurably by des(1–3)IGF-I. The major IGF-binding protein circulating in blood, IGFBP-3, demonstrated a similar pattern of change. A significant (P<0·05) protection of body weight was achieved in the low dose IGF-I and des(1–3)IGF-I groups, but only after differences in food intake had been eliminated by analysis of covariance. Nitrogen balances were not significantly different unless analysis of covariance was used to adjust for the nitrogen intakes, whereupon all treatment groups showed improved balance, especially the animals treated with the low IGF-I dose and des(1–3)IGF-I (both P<0·01). The rate of muscle protein breakdown calculated from the urinary excretion of 3-methylhistidine was not significantly altered by the treatments, but fell progressively throughout the 7 days. The fractional rate of muscle protein synthesis measured on the final day was increased by 31, 26 and 21% respectively by the low and high doses of IGF-I and by des(1–3)IGF-I. Organ weights (g/kg body weight) showed no effects of IGF-I treatment except for 16% increases in the weight of kidneys in the high dose IGF-I and the des(1–3)IGF-I groups. Carcass analyses demonstrated higher water and lower fat contents (all P< 0·01) in the same groups. These results suggest that exogenous IGF-I and especially des(1–3)IGF-I can partly protect body protein reserves during nitrogen restriction. Journal of Endocrinology (1991) 128, 97–105


1990 ◽  
Vol 124 (1) ◽  
pp. 151-158 ◽  
Author(s):  
R. A. Siddiqui ◽  
H. T. Blair ◽  
S. N. McCutcheon ◽  
D. D. S. Mackenzie ◽  
P. D. Gluckman ◽  
...  

ABSTRACT A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P<0·05) but not by sex. Significant (P< 0·001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P< 0·001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant. Nose–anus length was significantly (P<0·01) affected by sex and line from 42 to 105 days of age, but anus–tail length was not affected by sex or line at any age. Effects of sex and line on empty (digesta-free) body weight and wet weights of carcass and skin plus viscera fractions followed a pattern similar to those of liveweights. The effects of sex and line on protein, water and fat content also paralleled their effects on body size. Differences between males and females, and between the lines, in amount of protein, water and fat could be entirely accounted for by the corresponding differences in body weight. It is concluded from these results that divergent selection on the basis of plasma IGF-I at 42 days of age resulted in lines of animals differing in plasma IGF-I from 21 days of age until maturity. These divergent concentrations of IGF-I are associated with differences between the lines in body growth, particularly during the period of accelerated growth at puberty, but not with changes in body composition. Journal of Endocrinology (1990) 124, 151–158


1991 ◽  
Vol 128 (2) ◽  
pp. 181-186 ◽  
Author(s):  
J. J. Bass ◽  
J. M. Oldham ◽  
S. C. Hodgkinson ◽  
P. J. Fowke ◽  
H. Sauerwein ◽  
...  

ABSTRACT The effect on young lambs of 0·25 mg recombinant bovine GH (bGH)/kg per day on plasma concentrations of insulin-like growth factor-I (IGF-I), glucose, specific hepatic GH binding and body composition changes was examined at two levels of nutrition (lucerne pellets; 3 and 1·7% of body weight/day). Lambs on low levels of nutrition had low plasma IGF-I (P < 0·001). Plasma concentrations of IGF-I were increased by bGH treatment at both levels of nutrition, with the high nutrition group showing the greatest IGF-I response after 3 and 40 days of bGH treatment. Plasma glucose, after 40 days, was higher overall (P < 0·05) in lambs on high nutrition. bGH treatment increased plasma glucose, with the response being greater in the well-fed lambs. Specific binding of GH to liver membranes was highest in lambs on high nutrition and on bGH treatment; no significant interaction between nutrition and bGH treatment was detected, indicating that specific binding of GH was increased proportionally by bGH at both nutritional levels. The major change in body composition was the reduced level of fatness in lambs treated with bGH. There was no significant effect of bGH on body weight although bGH treatment tended to increase weight gain of well-fed lambs and decreased weight loss of poorly nourished lambs. The results show that, although there was a significant (P < 0·05) bGH/nutrition interaction for IGF-I there was no such interaction for body weight/components or specific GH binding to the liver. The results indicate that an increase in plasma IGF-I does not necessarily result in increases in growth or changes in carcass composition. Journal of Endocrinology (1991) 128, 181–186


1997 ◽  
Vol 272 (5) ◽  
pp. R1532-R1539 ◽  
Author(s):  
A. F. Philipps ◽  
G. G. Anderson ◽  
B. Dvorak ◽  
C. S. Williams ◽  
M. Lake ◽  
...  

Insulin-like growth factor I (IGF-I), a potent mitogenic peptide, is present in considerable quantities in most mammalian milks, but its importance for the neonate is unknown. To test the hypothesis that milk-borne IGF-I is an important factor in the regulation of neonatal growth, as well as that of the gastrointestinal tract, rat pups were fed a rat milk substitute (RMS) devoid of growth factors via gastrostomy. These animals were compared with those given RMS supplemented with recombinant human IGF-I added at a concentration of 500 ng/ml. Animals given RMS + IGF-I gained mere weight than controls, although skeletal growth as represented by elongation of the tail was no different. Animals fed RMS + IGF-I had increased brain and liver wet weights as well as increased liver and small intestine protein contents. Serum IGF-I concentrations in the IGF-I-supplemented group were more than twofold above RMS controls and were similar to dam-fed rat pups. Semiquantification of serum IGF-binding proteins (IGFBP) in these animals documented that in IGF-I-supplemented pups the amount of 38- to 40-kDa molecular mass IGFBP species was also greater than in RMS controls. The rate of migration of enterocytes from crypts in duodenum and proximal jejunum was greater in IGF-I-supplemented animals than in rats fed RMS alone. These studies suggest that milk-borne IGF-I is important in modulation of somatic and gastrointestinal tract growth in the neonatal rat.


1988 ◽  
Vol 119 (2) ◽  
pp. 281-285 ◽  
Author(s):  
M. D. Holland ◽  
K. L. Hossner ◽  
G. D. Niswender ◽  
T. H. Elsasser ◽  
K. G. Odde

ABSTRACT A quantitative, repeatable, heterologous radioimmunoassay (RIA) for insulin-like growth factor-I (IGF-I) was developed for bovine serum. Untreated serum could not be assayed due to interference by IGF-I-binding protein. Serum acidified to pH 3·6 in glycine–HCl (0·1 mol/l) for 24 h at 37 °C and neutralized with NaOH produced inhibition curves non-parallel to the [Thr59]-IGF-I standard. Neutralization by 40-fold dilution of acidified serum samples with assay buffer produced inhibition curves nearly parallel to the IGF-I standard. Complete parallelism was achieved by utilizing preprecipitated normal rabbit serum–sheep anti-rabbit γ-globulin to separate antibody-bound 125I-labelled IGF-I from free 125I-labelled IGF-I. Recovery of IGF-I (1·3–52·3 fmol) added to serum was quantitative. The sensitivity of the RIA (n = 6) was 8·25 ± 0·17 (s.e.m.) fmol. Intra- and interassay coefficients of variation were 3·03 and 4·95% respectively. Serum IGF-I levels measured in beef calves at weaning were positively correlated with weaning weight, total weight gain from birth to weaning and average daily weight gain. In conclusion, a heterologous RIA for IGF-I in beef serum which is sensitive, accurate, precise and repeatable has been developed. J. Endocr. (1988) 119, 281–285


2019 ◽  
Vol 122 (07) ◽  
pp. 734-744 ◽  
Author(s):  
Yuanfa He ◽  
Shuyan Chi ◽  
Beiping Tan ◽  
Xiaohui Dong ◽  
Qihui Yang ◽  
...  

AbstractAn 8-week feeding experiment was conducted to investigate the effects of dl-methionine (Met) supplementation in a low-fishmeal diet on growth, key gene expressions of amino acid transporters and target of rapamycin (TOR) pathway in juvenile cobia, Rachycentron canadum. Seven isonitrogenous and isolipidic diets were formulated, containing 0·72, 0·90, 1·00, 1·24, 1·41, 1·63 and 1·86 % Met. Weight gain and specific growth rates increased gradually with Met levels of up to 1·24 % and then decreased gradually. In dorsal muscle, mRNA levels of ASCT2 in the 1·00 % Met group were significantly up-regulated compared with 0·72, 1·63, and 1·86 %. The insulin-like growth factor-I (IGF-I) mRNA levels in the dorsal muscle of fish fed 1·00 and 1·24 % Met were higher than those in fish fed other Met levels. In addition, fish fed 1·24 % Met showed the highest mRNA levels of TOR and phosphorylation of TOR on Ser2448. The phosphorylation of ribosomal p70-S6 kinase (S6K) on Ser371 in the dorsal muscle of fish fed 1·86 % Met was higher than those in the 0·72 % group. In conclusion, straight broken-line analysis of weight gain rate against dietary Met level indicates that the optimal Met requirement for juvenile cobia is 1·24 % (of DM, or 2·71 % dietary protein). Met supplementation in a low-fishmeal diet increased cobia growth via a mechanism that can partly be attributed to Met’s ability to affect the TOR/S6K signalling pathway by enhancing ASCT2 and IGF-I transcription in cobia dorsal muscle.


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