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

• Published in: American journal of physiology: endocrinology and metabolism 2004-12, Vol.287 (6), p.E1039-E1048
• Main Authors: Ameen, Caroline, Linden, Daniel, Larsson, Britt-Mari, Mode, Agneta, Holmang, Agneta, Oscarsson, Jan
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase; Acetyl-CoA Carboxylase - genetics; Animals; Antigens; biosynthesis; blood; CCAAT-Enhancer-Binding Proteins; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; CD95; Cells; Cells, Cultured; Cultured; Cytoplasmic and Nuclear; DNA-Binding Proteins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; fas Receptor - genetics; Female; Fysiologi; genetics; Glycerol-3-Phosphate O-Acyltransferase; Glycerol-3-Phosphate O-Acyltransferase - genetics; Growth Hormone; Growth Hormone - blood; Growth Hormone - pharmacology; Growth Hormone - secretion; Hepatocytes; Hepatocytes - metabolism; Insulin Resistance; Insulin Resistance - genetics; Lipids; Lipids - biosynthesis; Liver; Liver - metabolism; Liver X Receptors; Male; Medicin och hälsovetenskap; Messenger; metabolism; Orphan Nuclear Receptors; pharmacology; Physiology; Rats; Rats, Sprague-Dawley; Receptors; Receptors, Cytoplasmic and Nuclear - genetics; RNA; RNA, Messenger - metabolism; secretion; Sex Characteristics; Sprague-Dawley; Stearoyl-CoA Desaturase; Stearoyl-CoA Desaturase - genetics; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00059.2004

1 Wallenberg Laboratory for Cardiovascular Research and 2 Department of Physiology, Sahlgrenska University Hospital, SE-413 45 Goteborg; 3 AstraZeneca Research and Development, SE-431 83 Molndal; and 4 Department 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 Address for reprint requests and other correspondence: C. Améen, Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Univ. Hospital, SE-413 45 Göteborg, Sweden (E-mail: caroline.ameen{at}wlab.gu.se )