thesis
Lipoprotein metabolism in hypothyroidism : the contribution of growth hormone
- Publication date
- 16 December 1992
- Publisher
- 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.