Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver.
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-alpha (LXRalpha) 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 LXRalpha 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 LXRalpha mRNA but is associated with decreased insulin sensitivity.
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. caroline.ameen@wlab.gu.se
Caroline
C
Améen
Daniel
D
Lindén
Britt-Mari
BM
Larsson
Agneta
A
Mode
Agneta
A
Holmäng
Jan
J
Oscarsson
D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012727:Sex Characteristics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008055:Lipids; D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D019014:fas Receptor; D013006:Growth Hormone; D013230:Stearoyl-CoA Desaturase; D005992:Glycerol-3-Phosphate O-Acyltransferase; D000103:Acetyl-CoA Carboxylase