Modulation of the peroxisomal gene expression pattern by dehydroepiandrosterone and vitamin D: therapeutic implications

Abstract

Peroxisomes are ubiquitous organelles required for several metabolic functions. Their dysfunction is responsible for a group of human inherited disorders. In the search for endogenous factors regulating the peroxisomal compartment in normal liver, we treated female rats with dehydroepiandrosterone (DHEA) and 25-hydroxycholecalciferol for 1 and 6 days. Relative transcription levels of 39 selected genes were evaluated by real-time quantitative RT-PCR analysis. Catalase (peroxisomal marker)-specific activity was assayed in total liver homogenate and peroxisomes were visualized by catalase localization. DHEA induced peroxisome proliferation and raised catalase specific activity. Expression levels of 16 (of which 11 were peroxisomal) genes were altered. Pex 11, acyl-CoA oxidase, -and -multifunctional enzyme, thiolase 1, phytanoyl-CoA hydroxylase, 70 kDa peroxisomal membrane protein and very long chain acyl-CoA synthetase were upregulated, three others were downregulated. Vitamin D caused downregulation of six genes. Administration of vitamin D to peroxisomal disorder patients may be contraindicated. The adrenocortical hormone DHEA is a potential natural regulator of the peroxisomal compartment. Its therapeutic use in X-linked adrenoleukodystrophy, some other -oxidation defects and classical Refsum should be considered.

Effects of Dehydroepiandrosterone Administration on Rat Hepatic Metabolism Following Thermal Injury

“…4), namely, a reduction in the output of aspartate and glutamate, the glutaminase reaction, and the output of ammonia. These changes could be due to metabolism of the PG itself, as it has previously been noted that PG in the perfusate can affect the redox state of the perfused rat liver [54] and that PG in the diet can cause changes in hepatic gene expression [55]. PG (with or without DHEA) injections were carried out under halothane anesthesia; therefore, we cannot exclude an effect of the anesthetic, as it is metabolized by the liver [56].…”

Dehydroepiandrosterone modifies rat fatty acid composition of serum and different adipose tissue depots and lowers serum insulin levels

“…It has been reported that these steroids reduce AT cellularity (Ryu et al 2003), inhibit preadipocyte differentiation in vitro (Lea-Currie et al 1998), stimulate lipolysis (Tagliaferro et al 1995, Hernández-Morante et al 2008, and alter AT gene expression (Kajita et al 2003, Sánchez et al 2008. In addition, DHEA-S can modulate fatty acid (FA) metabolism, through up-regulation of hepatic enzymes involved in b-oxidation (Waxman 1996, Depreter et al 2002.…”

Adrenal steroids in adrenomyeloneuropathy

“…ALD is a peroxisomal disease and, in animals, DHEAS induces peroxisomal proliferation and the expression of enzymes involved in fatty acid metabolism [12].…”