Involvement of hepatic IL-1 in the strain-dependent sex differences in serum total cholesterol levels in rats.
The strain and sex differences in serum total cholesterol (TC) levels were examined in F344 and Sprague-Dawley (SD) rats. A sex difference (male<female) was observed in F344 rats but not in SD rats. The strain-dependent sex difference (male<female) was also observed in the constitutive gene expression level of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), a rate-limiting enzyme for cholesterol biosynthesis, but not in the expression of hepatic cholesterol 7α-hydroxylase, a rate-limiting enzyme for cholesterol catabolism (bile acid biosynthesis from cholesterol). The strain-dependent sex difference in hepatic HMGR gene expression was closely correlated with the levels of hepatic interleukins (ILs), especially of IL-1α, which acts as a positive regulator for the hepatic HMGR gene. Hepatic IL-1α protein expression was higher in female F344 rats than in male F344 rats and compared with male and female SD rats. Similar to hepatic IL-1α protein expression, serum TC levels were highest in female F344 rats than in the other groups of rats. Serum TC and hepatic IL-1α levels in male F344 rats were similar to those in male and female SD rats. The present findings demonstrate for the first time that strain-dependent sex difference in serum TC level between F344 and SD rats is, at least in part, related to difference in the IL-1α-mediated HMGR gene expression level in the liver.
Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka.
Yoichi
Y
Kumagai
Masashi
M
Sekimoto
Minako
M
Okamoto
Ryuzo
R
Kurita
Misaki
M
Kojima
Masakuni
M
Degawa
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis; D004958:Estradiol / Q000097:blood; D005260:Female; D015870:Gene Expression; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis; D053582:Interleukin-1alpha / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013045:Species Specificity; D013739:Testosterone / Q000097:blood
C000594089:IL1B protein, rat; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D013739:Testosterone; D004958:Estradiol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase