Effects of a polyclonal antiserum to rat growth hormone on circulating insulin-like growth factor (IGF)-I and IGF-binding protein concentrations and the growth of muscle and bone

Abstract

A polyclonal antiserum to rat GH (anti-rGH) injected into rats for 3 or 8 weeks markedly reduced the weight, total protein and RNA content of muscles of the hind limb. These effects were prevented when bovine GH (bGH) was administered simultaneously. In a second experiment, the effects of 8 weeks of treatment with anti-rGH on the growth of the whole body, muscle and bone were investigated. Body weights of rats were decreased by 58% by treatment with anti-rGH; muscle weights were reduced by slightly more than the decrease in body weight (by 64%, 65% and 61% respectively for plantaris, soleus and gastrocnemius). The weight of the tibia was decreased by 54%, its length was decreased by 23%, cortical width and overall width were reduced by 26% and 18% respectively, suggesting a possible role for GH in osteoclastic activity. Serum total insulin-like growth factor-I (IGF-I) concentrations were decreased by 80-90% in both experiments by anti-rGH; these changes were prevented in the first experiment by concurrent treatment with anti-rGH and bGH. The serum IGF-binding protein-3 (IGFBP-3) concentration was also decreased by anti-rGH in experiment 1 (by 86%); the response of the 28-32 kDa IGFBPs was smaller (-35%), and was restored to control values by simultaneous injection of bGH. Western immunoblotting using an antiserum to IGFBP-2 showed that there was a marked decrease from neonatal to adult stages which was independent of anti-rGH treatment. This clearly demonstrated a dissociation of the reciprocal relationship supposed to exist between IGFBPs-2 and -3. The 24 kDa IGFBP-4 was unaffected by anti-rGH but replacement therapy with bGH doubled its concentration. Although the effects on body and muscle weight were prevented when rats were given anti-rGH and bGH simultaneously, the possibility of mediation by other hormones cannot be precluded.

Differentially expressed genes and signalling pathways are involved in mouse osteoblast-like MC3T3-E1 cells exposed to 17-β estradiol

“…17 Oestrogen deficiency also downregulates the transcription of the gene for insulin-like growth factor 1, reducing bone formation as a result. 18 Various intermediary pathways have been found that participate in the oestrogen-mediated biological responses of osteoblasts, such as transforming growth factor (TGF)-β, the Wnt signalling pathways and apoptosis.…”

Functional proteome of bones in rats with osteoporosis following ovariectomy

“…These cytokines were determined to have strong action on bone absorbing and restrain bone forming (Cohen-Solal et al, 1998;Cohen-Solal et al, 1993;Cheleuitte et al, 1998). The estrogen deficiency also down-regulated the gene transcription level of insulin like growth factor (IGF1) following reduced bone forming (Palmer et al, 1994). Furthermore, osteoporosis has been found to be under the control of a large number of genes.…”

Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice

“…Similarly, the concentration of IGFBP-4 in serum of rats doubled after treatment with bGH (38). As IGFBP-4 is known to inhibit actions of IGFs (for review, see Ref.…”

“…After weaning at 3 weeks of age, the animals were fed a standard rodent diet (Altromin 1324; Altromin, Lage, Germany: 185.5 g protein, 535.6 g disaccharide, 38.0 g fat, 590 kJ convertible energy per kg). During week 14, a diet high in protein and low in carbohydrates (Altromin 1001; 547.2 g protein, 6.7 g disaccharide, 111.6 g fat, 753 kJ convertible energy per kg) was fed to stimulate PEPCK promoter-controlled transgene expression.…”