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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/E1039    most recent 00059.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Améen, C. Articles by Oscarsson, J. Search for Related Content PubMed PubMed Citation Articles by Améen, C. Articles by Oscarsson, J.

Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver

¹Wallenberg Laboratory for Cardiovascular Research and ²Department of Physiology, Sahlgrenska University Hospital, SE-413 45 Goteborg; ³AstraZeneca Research and Development, SE-431 83 Molndal; and ⁴Department of Medical Nutrition, Karolinska Institutet, Novum, SE-141 86 Huddinge, Sweden

Submitted 6 February 2004 ; accepted in final form 14 July 2004

We investigated whether the sexually dimorphic secretory pattern of growth hormone (GH) in the rat regulates hepatic gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes. SREBP-1c, fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT) mRNA were more abundant in female than in male livers, whereas acetyl-CoA carboxylase-1 (ACC1) and stearoyl-CoA desaturase-1 (SCD-1) were similarly expressed in both sexes. Hypophysectomized female rats were given GH as a continuous infusion or as two daily injections for 7 days to mimic the female- and male-specific GH secretory patterns, respectively. The female pattern of GH administration increased the expression of SREBP-1c, ACC1, FAS, SCD-1, and GPAT mRNA, whereas the male pattern of GH administration increased only SCD-1 mRNA. FAS and SCD-1 protein levels were regulated in a similar manner by GH. Incubation of primary rat hepatocytes with GH increased SCD-1 mRNA levels and decreased FAS and GPAT mRNA levels but had no effect on SREBP-1c mRNA. GH decreased hepatic liver X receptor- (LXR) mRNA levels both in vivo and in vitro. Feminization of the GH plasma pattern in male rats by administration of GH as a continuous infusion decreased insulin sensitivity and increased expression of FAS and GPAT mRNA but had no effect on SREBP-1c, ACC1, SCD-1, or LXR mRNA. In conclusion, FAS and GPAT are specifically upregulated by the female secretory pattern of GH. This regulation is not a direct effect of GH on hepatocytes and does not involve changed expression of SREBP-1c or LXR mRNA but is associated with decreased insulin sensitivity.

growth hormone; hypophysectomy; acetyl-CoA carboxylase; fatty acid synthase; stearoyl-CoA desaturase; glycerol-3-phosphate acyltransferase; liver X receptor-; insulin sensitivity

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