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Am J Physiol Endocrinol Metab (July 27, 2004). doi:10.1152/ajpendo.00059.2004
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Submitted on February 6, 2004
Accepted on July 14, 2004

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

Caroline Ameen1*, Daniel Linden2, Britt-Mari Larsson3, Agneta Mode4, Agneta Holmang3, and Jan Oscarsson5

1 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Goteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Goteborg, Sweden
2 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Goteborg, Sweden; AstraZeneca Research and Development, Molndal, Sweden
3 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Goteborg, Sweden
4 Department of Medical Nutrition, Karolinska Institutet, Stockholm, Sweden
5 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Goteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Goteborg, Sweden; AstraZeneca Research and Development, Molndal, Sweden

* To whom correspondence should be addressed. E-mail: caroline.ameen{at}wlab.gu.se.

We investigated if the sexually dimorphic secretory pattern of 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, while acetyl-CoA carboxylase-1 (ACC-1) 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, ACC-1, FAS, SCD-1 and GPAT mRNA, while the male pattern of GH administration only increased 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, decreased FAS and GPAT mRNA levels, but had no effect on SREBP-1c mRNA. GH decreased hepatic LXR{alpha} 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, increased expression of FAS and GPAT mRNA, but had no effect on SREBP-1c, ACC-1, SCD-1 or LXR{alpha} 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{alpha} mRNA, but is associated with decreased insulin sensitivity.




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