Growth hormone regulation of insulin-like growth factor-I mRNA in rat adipose tissue and isolated rat adipocytes

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.

Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH

“…GH stimulates lipolysis in mature adipocytes and primary preadipocytes but promotes adipogenesis in preadipocyte cell lines. Mouse prolactin and mouse GH stimulate IGF1 mRNA in differentiated cells but not in undifferentiated cells (18,19). GH increases lipolysis as a direct effect of GH on adipocytes, as well as a decrease of lipoprotein lipase activity, diminishing the flow of fatty free acids to the adipocyte.…”

Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus

“…IGF-I is expressed in most tissues in the body, including large organs like skeletal muscle (Isgaard et al, 1988), adipose tissue (Vikman et al, 1991), and liver (Schwander et al, 1983;D'Ercole et al, 1984;Humbel, 1990). However, the liver-derived IGF-I is the principal source of circulating IGF-I that is able to affect the brain (Schwander et al, 1983;Sjögren et al, 1999).…”

Profiles of Growth Hormone (GH)-regulated Genes Reveal Time-dependent Responses and Identify a Mechanism for Regulation of Activating Transcription Factor 3 By GH

“…5 While many of the genes corresponding to the 561 probe sets identified by this microarray analysis have not previously been identified as responsive to GH in adipocytes, documented GH-responsive genes were also identified. For example, GH induced the expression of the gene for insulin-like growth factor-I at 48 h, as seen in liver and adipose tissue from rodents (27,28). Expression of the genes for GHR (29) and the acid labile subunit, which complexes with circulating insulin-like growth factor-I (30), also increased after 48 h of GH.…”