Message Number: FHL2979 | New FHL Archives Search
From: "Sukie Crandall"
Date: 2007-11-10 23:32:25 UTC
Subject: [ferrethealth] Re: simple sugars and sex steroids (SHBG research press release)

--- In, Sukie Crandall <sukiec@...> wrote:
> *****IF***** this holds for ferrets, too, then it says that sugars or =

> fruits as treats could worsen the effects of adrenal neoplasia by=20
> reducing a genetic regulator that can help keep sex steroid levels=20
> lower...

Here is the abstract:

J Clin Invest. 2007 Nov 8; [Epub ahead of print]Links
Monosaccharide-induced lipogenesis regulates the
human hepatic sex hormone-binding globulin gene.

Selva DM, Hogeveen KN, Innis SM, Hammond GL.
Department of Obstetrics and Gynecology, University
of British Columbia, and Child and Family Research Institute,
Vancouver, British Columbia, Canada. University of Western
Ontario, London, Ontario, Canada. UMR-INSERM U449,
Facult=E9 de M=E9decine RTH La=EBnnec, Lyon, France. Department
of Pediatrics, University of British Columbia, and Child and
Family Research Institute, Vancouver, British Columbia, Canada.
The liver produces plasma sex hormone-binding globulin (SHBG),
which transports sex steroids and regulates their access to tissues.
In overweight children and adults, low plasma SHBG levels are a
biomarker of the metabolic syndrome and its associated
pathologies. Here, we showed in transgenic mice and HepG2
hepatoblastoma cells that monosaccharides (glucose and fructose)
reduce human SHBG production by hepatocytes. This occurred via
a downregulation of hepatocyte nuclear factor-4alpha (HNF-4alpha)
and replacement of HNF-4alpha by the chicken OVA upstream
promoter-transcription factor 1 at a cis-element within the human
SHBG promoter, coincident with repression of its transcriptional
activity. The dose-dependent reduction of HNF-4alpha levels in
HepG2 cells after treatment with glucose or fructose occurred in
concert with parallel increases in cellular palmitate levels and could
be mimicked by treatment with palmitoyl-CoA. Moreover, inhibition
of lipogenesis prevented monosaccharide-induced downregulation
of HNF-4alpha and reduced SHBG expression in HepG2 cells. Thus,
monosaccharide-induced lipogenesis reduced hepatic HNF-4alpha
levels, which in turn attenuated SHBG expression. This provides a
biological explanation for why SHBG is a sensitive biomarker of the
metabolic syndrome and the metabolic disturbances associated with
increased fructose consumption.
PMID: 17992261 [PubMed - as supplied by publisher]


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