Sex difference in hepatic microsomal triglyceride transfer protein expression is determined by the growth hormone...

Microsomal triglyceride transfer protein (MTP) is essential and rate limiting for the assembly and secretion of apoB-containing lipoproteins. The aim of this study was to investigate whether gender and GH influence hepatic MTP expression. We used intact, gonadectomized, or hypophysectomized (Hx) adult Sprague Dawley rats. Gonadal steroids and insulin were given as a daily sc injection for 7 d. GH was given for 7 d either as a continuous infusion or as two daily injections (2 x GH) to mimic the feminine and masculine GH secretory patterns, respectively. MTP mRNA and MTP and protein disulfide isomerase protein expression was measured. MTP mRNA, and protein expression was higher in females than in males. Gonadectomy abolished the sex difference, and treatment with gonadal steroids restored the sex difference in MTP mRNA levels. MTP mRNA expression was not influenced in either sex by 2 wk of cholesterol (1% wt/wt) feeding. Hx decreased MTP mRNA in females but not in males. A continuous GH infusion increased MTP mRNA and protein expression in intact males but not in females. A continuous GH infusion to Hx females normalized MTP mRNA and protein expression, but 2 x GH had no effect. Also, insulin treatment had no effect. In summary, MTP expression is sex differentiated and regulated by the sexually dimorphic secretory pattern of GH at the level of mRNA. These results are important for the understanding of the effects of gender and GH in the regulation of very low-density lipoprotein assembly and secretion.