UP-REGULATION OF COLLAGEN TYPE-I GENE-EXPRESSION IN THE VENTRICULAR MYOCARDIUM OF THYROIDECTOMIZED MALE AND FEMALE RATS

It is established that thyroxine-induced ventricular hypertrophy is as sociated with downregulation of collagen type I gene expression and in creased collagen turnover in the ventricular tissue. The present study was undertaken to test the hypothesis that circulating thyroid hormon es may have a regulatory impact on the biosynthesis of the collagen ma trix in the heart. To this end, we determined collagen gene expression and deposition in the hearts of male and female Sprague-Dawley rats a fter surgical thyroidectomy. The serum levels of 3, 3'5-triiodothyroni ne (T-3) and 3,5,3',5'-tetraiodothyronine (T-4) in thyroidectomized an d age/sex-matched sham-operated rats were determined by radioimmunoass ay and fluorescence analysis of the serum, respectively. On day 14 pos t-surgery, the plasma levels of both T-3 and T-4 in thyroidectomized r ats were decreased by greater than 85% compared with those in matching sham-operated control rats. At this time, Northern analysis of ventri cular RNA from thyroidectomized rats showed a 160% (P=0.0079) increase for pro alpha(1) (I) and a 43% increase (P=0.0484) for pro alpha(2) ( I) collagen mRNAs in the ventricular tissue of male rats compared with that in the heart of age-matched, sham-operated control rats. In the female rats, thyroidectomy led to 63% (P = 0.0469) increase in the abu ndance of pro alpha(1) (I) collagen and 50% (P=0.034) increase for pro alpha(2) (I) collagen in ventricular tissue, At the protein level, th e amount of collagen type I as determined by immune-slot blotting of v entricular homogenates, was increased in the ventricular tissue of bot h male (131%. P=0.0371) and female (108%, P=0.0464) rats. Comparison o f the changes in males nu females showed relatively greater increases in the level of collagen type I mRNA and protein in ventricular tissue of thyroidectomized males. Of particular note, were the increases in the immunoreactive TGF-beta in ventricular tissue of thyroidectomized male and female rats which showed a pattern similar to that of changes in collagen type I. Immunofluorescent light microscopy of frozen hear t sections, showed significant remodeling of the type I collagen fiber s in the ventricular myocardium of thyroidectomized rats compared with age/sex-matched sham-operated rat heart, Together, these findings sug gest that circulating thyroid hormones play a role in physiological re gulation of collagen type I biosynthesis in the heart and this role ma y vary in males and females. They further suggest that normal producti on of collagen matrix in the heart may be dependent on the functional status of thyroid hormones. (C) 1996 Academic Press Limited