In Vivo Regulation of Hepatic Insulin-Like Growth Factor-1 Messenger Ribonucleic Acids with Thyroid Hormone.

Abstract

Insulin-like growth factor-1 (IGF-1) is synthesized primarily by the liver in response to growth hormone (GH). Thyroid hormone plays a major role in mediating pituitary GH secretion. In order to clarify the effect of thyroid hormone on IGF-1 gene expression, we measured hepatic IGF-1 mRNA levels in rats with thyroid dysfunction. Female Wistar rats were rendered hypothyroid by surgical thyroidectomy or hyperthyroid by daily injections of thyroxine (12 micrograms/day) for 2 weeks. Northern gel analysis of hepatic poly (A) RNA revealed the multiple sizes of the RNA transcripts ranging from 1.6 to 9.0 kb. After 4 weeks, hepatic IGF-1 mRNA levels were suppressed in hypothyroid rats, to less than 20% of control euthyroid animals. These suppressed mRNA levels were restored to euthyroid levels by thyroid hormone replacement for 2 weeks. Hyperthyroid rats, however, did not contain altered levels of hepatic IGF-1 mRNA as compared to euthyroid rats. The gamma-actin mRNA hybridization signal was not altered in hypothyroid or hyperthyroid rats. These results suggest that thyroid hormone regulates the in vivo expression of hepatic IGF-1 mRNA, probably through the mechanism of GH regulation.

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

“…In the hypothy¬ roid group, endocrine changes in the IGF-I axis appeared to be consistent with this finding. Liver IGF mRNA levels were only 37% of those of control animals and serum IGF-I levels were 30% of those of controls, confirming recent work by Harakawa et al (1990). There was a significant correlation between the densitometry signals of specific liver IGF-I mRNA bands in all groups and serum IGF-I levels, in keeping with the hypothesis that the liver is the major source of 'endocrine' IGF-I.…”

Influence of hypothyroidism on circulating concentrations and liver expression of IGF-binding proteins mRNA from neonatal and adult rats

“…Low plasma IGF-I and reduced IGF bioactivity have been reported in hypothyroid patients, whereas high plasma IGF-I concentrations and low bioactivity (Miell et al 1993) have been observed in hyperthyroid patients. Similar changes have been described in rats (Burstein et al 1979), and a decrease in hepatic IGF-I mRNA expression has been reported in experimental hypothyroid animals (Harakawa et al 1990). In addition, thyroid status is intimately involved in the regulation of glucose and insulin homeostasis (Lenzen & Bailey 1984), and reduced IGF-I has been widely reported in experimental models of undernutrition and diabetes (Rivero et al 1995, Goya et al 1996, 1999, because the rates of synthesis and secretion of IGF-I/IGFBPs depend also upon the availability of adequate nutrient intake (Rosenfeld et al 1990, Clemmons & Underwood 1991, Thissen et al 1994, Jones & Clemmons 1995, Rajaran et al 1997.…”

Effect of chronic thyroxine treatment on IGF-I, IGF-II and IGF-binding protein expression in mammary gland and liver during pregnancy and early lactation in rats

“…Although hypothyroidism lowers circulating and liver IGF-I concentrations, hyperthyroidism does not seem to modify serum or hepatic levels of this hormone in male or non-pregnant rats (7,49,50). We also observed no significant modifications in liver mRNA concentration of IGF-I in virgin rats or during pregnancy, but the postpartum increase was advanced, perhaps reflecting the advancement in luteolysis and parturition (3).…”