Studies on gene expression in calvaria and serum levels of insulin-like growth factor-I and bone Gla protein in the methimazole-induced congenital hypothyroid rat.

Abstract

In this study, we determined gene expression of both insulin-like growth factor (IGF)-I and bone Gla protein (BGP; osteocalcin) in calvaria in comparison with their serum levels in methimazole (MMI)-induced congenital hypothyroid (CHT) rats during the first 4 weeks of life. Pups from the MMI-treated dams revealed congenital hypothyroidism with cretinoid physical appearance and showed significant growth retardation compared to the controls. The expression of mRNA for IGF-I in the CHT pups lacked the age-associated increase with a little spurt in their somatic growth rate, although the expression in the controls increased steeply (from 1.86-fold on postnatal day 21 to 3.52-fold on day 28 compared to the day 7 value; P < 0.01) according to the spurt in their growth. Moreover, serum IGF-I levels in the CHT rats were significantly lower than those in the controls on postnatal day 28 (63.0 +/- 8.0 ng/ml vs. 285.0 +/- 33.2 ng/ml, respectively; P < 0.01). Both BGP gene expression in calvaria and serum intact molecular BGP levels determined by a newly developed ELISA (164.4 +/- 15.5 ng/ml in the CHT rat vs. 238.6 +/- 17.8 ng/ml in the control on postnatal day 28; P < 0.01) correlated well with the somatic growth in the two groups and clearly demonstrated impaired osteogenesis in the CHT rats. Further studies are needed to clarify how hypothyroidism affects somatic growth and bone metabolism; it is particularly important to understand the autocrine/paracrine mechanisms of action of IGFs in the bone matrix turnover, in vivo.