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

Abstract

. Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver. Am J Physiol Endocrinol Metab 287: E1039 -E1048, 2004. First published July 27, 2004 doi:10.1152/ ajpendo.00059.2004.-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 GROWTH HORMONE (GH) plays an important role in the regulation of lipid metabolism. GH has lipolytic and antilipogenic effects in adipose tissue (6) that contribute to the decreased body fat mass observed after GH treatment (2, 42). Elevation of plasma GH levels also results in increased plasma insulin levels and insulin resistance (6). The increased insulin secretion can be explained by a direct effect of GH on the pancreatic ␤-cells (33, 40), whereas the insulin resistance may be explained by increased fatty acid oxidation in some (34), but not all, situations (18, 37).GH secretion from the pituitary is sexually differentiated in all mammals, but the difference is particularly pronounced in rodents (8,17,21). In female rats, the GH secretion is frequent and nearly continuous with high basal levels, whereas GH is secreted as regular, high-amplitude pulses with low or undetectable levels between peaks in males (8, 46). Several hepatic functions that are sex differentiated a...

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“…RNA quality assessment and all other procedures specific to the handling of microarray chips and reagents were performed by the University of Michigan Comprehensive Cancer Center Microarray Core facility (http:// www.umich.edu/ϳcaparray). Complementary DNA probes were synthesized from pooled RNA, which were grouped as shown in Supplemental Table S1, 1 and hybridized in duplicate to Affymetrix Mouse Genome 430 2.0 Arrays. The data were first analyzed for quality and converted to relative expression values using the robust multiarray average (RMA) method of Irizarry et al (12).…”

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Sex Differences in the Expression of Hepatic Drug Metabolizing Enzymes

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