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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Acetyl-CoA Carboxylase

genetics

Animals

Antigens

CD95

genetics

CCAAT-Enhancer-Binding Proteins

genetics

metabolism

Cells

Cultured

DNA-Binding Proteins

genetics

metabolism

Female

Glycerol-3-Phosphate O-Acyltransferase

genetics

Growth Hormone

blood

pharmacology

secretion

Hepatocytes

metabolism

Insulin Resistance

genetics

Lipids

biosynthesis

Liver

metabolism

Male

RNA

Messenger

metabolism

Rats

Rats

Sprague-Dawley

Receptors

Cytoplasmic and Nuclear

genetics

Sex Characteristics

Stearoyl-CoA Desaturase

genetics

Sterol Regulatory Element Binding Protein 1

Transcription Factors

genetics

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)