Long-term reductions in GH, insulin-like growth factor-I and body weight gain in rats treated neonatally with antibodies to rat GH

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A specific antiserum to rat GH (anti-rGH) raised in sheep was used in young male and lactating rats. In both models a group of rats was found which appeared to generate a low response (low responders) to the injected sheep immunoglobulin, and was characterized by the ability of the antiserum to cause inhibition of growth for more than 21 days in the male rats, and to abolish milk yield when prolactin concentrations were lowered in the females. In the groups which generated a high response to the anti-rGH (high responders), growth was retarded for only 2-3 days in male rats, with a moderate milk yield maintained in lactating animals. The low-response animals were found to have a significantly longer half-life for circulating anti-rGH, when compared with the high-response animals. After 21 days, in the age-matched male rats, levels of anti-rGH were undetectable in the high-responders, whereas the low-response animals, which were nearly 160 g lighter, still had approximately 4.5 ml anti-rGH/l in their circulation. This anti-rGH was still capable of neutralizing GH, as concentrations of insulin-like growth factor-I (IGF-I) were 13.6 +/- 3.5 (mean +/- S.E.M.) and 76.9 +/- 2.0 nmol/l in the low-response and high-response groups respectively. The reason for these differences would appear to be that the immune response mounted by these low-response animals to the exogenous sheep immunoglobulin (i.e. rat anti-sheep) 7 days after treatment was less than 10% of that seen in the high-response group.(ABSTRACT TRUNCATED AT 250 WORDS)

Section: Serum Analysesmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 97%

Long-term effect of a sheep antiserum to rat growth hormone in vivo in rats is explained by the rat anti-sheep immunoglobulin response

Madon

Panton²,

Flint³

1991

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“…Whilst the fat-mobilizing prop¬ erties of GH have been demonstrated in a large num¬ ber of studies conducted both in vivo and in vitro, studies supporting its role in adipocyte differentiation have been limited to in-vitro studies using cell lines (Morikawa et al 1982;Nixon & Green, 1984;Green et al 1985) and have not been confirmed using pri¬ mary cell cultures in vitro (Broad & Ham, 1984;Harrison et al 1985; Serrerò & Mills, 1987). For this reason we made use of a model, developed by us, with which we have demonstrated short-term effects of GH deficiency using specific antisera to rat GH (rGH) (Flint & Gardner, 1989;Gardner & Flint, 1990). We now demonstrate the long-term effects of GH defici¬ ency upon growth and adipose tissue development and provide the first evidence of a role for GH in adipose tissue differentiation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development

Flint

Gardner²

1993

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Neonatal female rats were treated for 3 weeks (short term) or 8 weeks (long term) with antiserum to rat GH (anti-rGH) with or without replacement therapy with recombinant bovine GH (bGH). Body weight gain and tail length were significantly suppressed within the first 3 weeks and were even more markedly suppressed when treatment was continued for 8 weeks. When treatment was stopped in short-term-treated animals the rate of body weight gain recovered, although without evidence of catch-up growth. These effects were all normalized by concurrent treatment with bGH. Long-term anti-rGH treatment caused a profound reduction (80%) in the number of differentiated adipocytes in two internal fat depots, whilst the subcutaneous depot was only moderately affected (20%). In contrast, after recovery from short-term treatment with anti-rGH, the internal depots were only marginally decreased in both weight and adipocyte numbers, whereas the subcutaneous depot was actually doubled in size compared with controls, due entirely to an increase in the number of differentiated adipocytes. These data clearly demonstrate for the first time that GH is required for the differentiation of adipocytes in vivo. In addition, the results demonstrate distinct effects at different anatomical sites and suggest that GH may be one factor responsible for the differences described in numerous metabolic parameters and hormonal sensitivities of adipose tissue derived from different locations within the body.

“…One alternative to hypophysectomy involves the use of antibodies against GH. Prolonged treatment with a polyclonal antiserum to rat GH resulted in a marked inhibition of rat growth (Gardner & Flint, 1990) but effects on specific tissues such as muscle were not investigated.…”

Section: Introductionmentioning

confidence: 99%

Effects of growth hormone and an antiserum to rat growth hormone on serum IGF-I and muscle protein synthesis and accretion in the rat

Palmer¹,

Flint²,

MacRae³

et al. 1993

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Rats were injected twice daily for up to 10 days with GH or with a polyclonal antiserum to rat GH, commencing at 21-22 days of age. Administration of bovine or human GH (1mg/day) improved whole body growth rates by 22% and 29% respectively. Plantaris muscle mass was also increased, by 7 and 14% respectively. Anti-GH injected twice daily resulted in a 7% decrease in body weight at 4 days and a 10% reduction by 10 days. Similar decreases were observed in the total protein content of plantaris and soleus muscles. The decrease in the fractional rate of protein synthesis was proportionately greater than the decline in protein content in plantaris muscle whereas in the soleus no change in the rate of protein synthesis was observed, suggesting that the effect on this muscle was due to an increase in the rate of protein degradation. Serum total IGF-I was unchanged by treatment with either GH or anti-GH while the amount of hepatic IGF-I mRNA was also unaffected by anti-GH injection. These data are consistent with a direct effect of GH or an effect mediated by an autocrine/paracrine mechanism of action on muscle but do not support a role for serum total IGF-I as an endocrine mediator of GH action.