Abstract
The effects of hypophysectomy and hormonal replacement therapy on insulin-like growth factor-I (IGF-I) mRNA in rat adipose tissue and adipocytes were studied. The effects of GH and IGF-I in vitro on IGF-I mRNA and IGF-I production were also studied in cultured rat adipocytes. Male rats were hypophysectomized at about 50 days of age and given replacement therapy with cortisol (400 micrograms/kg per day) and thyroxine (10 micrograms/kg per day). GH was given as a single i.v. or s.c. injection and also as a continuous s.c. infusion for 6 days. Epididymal fat pads were excised and used either for isolation of adipocytes or for determination of IGF-I mRNA in adipose tissue. A solution hybridization assay was used. The IGF-I mRNA content of adipocytes was analysed either immediately after isolation or after short-term (2-3 days) culture with or without GH or IGF-I. Hypophysectomy resulted in a marked decrease in IGF-I mRNA in both tissue and cells. Replacement therapy (in vivo) with cortisol and thyroxine alone had no effect, whereas additional treatment with GH caused a dose-dependent increase in IGF-I mRNA. IGF-I mRNA was also increased after a continuous s.c. infusion of GH. A single i.v. injection of GH (100 micrograms) resulted in an increase in IGF-I mRNA after approximately 2 h, with maximal levels around 6 h after the injection. In cultured adipocytes, addition of GH to the culture medium increased IGF-I mRNA in a dose-dependent manner and a marked increase was observed with a concentration of GH of 1 ng/ml. Addition of IGF-I (100 ng/ml) had no effect. The increase in IGF-I mRNA after addition of GH (100 ng/ml) was detectable after 3 h. The concentration of IGF-I in the culture medium was increased 24 h after the addition of GH. These results demonstrate that GH induces IGF-I mRNA in both adipose tissue and isolated fully differentiated adipocytes and that this increase in IGF-I mRNA results in increased IGF-I production.
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