Lipoprotein metabolism in hypothyroidism : the contribution of growth hormone
Lipoproteine metabolisme tijdens hypothyreoidie : de bijdrage van groeihormoon
Current data suggest a role for GH in the regulation of lipoprotein metabolism. In hypothyroidism not only the secretion of thyroid hormone, but also of GH is decreased. Generally the effects on plasma lipids seen in hypothyroid individuals are considered to be a consequence of decreased thyroid hormone levels. More then twenty years ago evidence was found that treatment of hypothyroid rats with GH in supraphysiologic doses affects plasma lipid concentrations, but whether a lack of GH (activity) is involved in the pathophysiology of lipid metabolism in hypothyroidism can not be answered from the present literature. The first aim was to investigate whether the changes occurring in lipid metabolism during hypothyroidism, merely result from a lack of thyroid hormone or are also attributable to a deficiency in GH-activity. In hypothyroid women the relationship between GH-activity (lGF-1) and plasma lipoproteins was evaluated (Chapter 2). The effects of a physiological dose of GH on lipoprotein concentrations during the hypothyroid status were studied in hypothyroid and hypophysectomized rats, as reported in Chapter 3. Furthermore, the effects on IGF-I and lipoproteins of substitution of hypothyroid rats with varying doses of thyroid hormone were studied (Chapter 4). The second aim was to investigate the mechanism by which GH can affect lipid metabolism, especially during hypothyroidism. The major cause of hypercholesterolemia in hypothyroidism is a decreased LDL catabolism in the liver. Hypothyroid rats were treated with GH and the effects of the hypothyroid status and GH treatment on liver cell LDL-receptor mRNA, LDL receptor expression and HMG-CoA reductase was studied, as described in Chapter 5. In Chapter 6 the effects of IGF-1, GH and T3 on the expression and function of the LDL-receptor in a human hepatoma derived cell line (HepG2) are described.