Abstract
Sex hormone-binding globulin (SHBG) is the main transport binding protein for sex steroid hormones in plasma and regulates their accessibility to target cells. Plasma SHBG is secreted by the liver under the control of hormones and nutritional factors. In the human hepatoma cell line (HepG2), thyroid and estrogenic hormones, and a variety of drugs including the antioestrogen tamoxifen, the phytoestrogen, genistein and mitotane (Op′DDD) increase SHBG production and SHBG gene promoter activity. In contrast, monosaccharides (glucose or fructose) effectively decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4α levels, a transcription factor that play a critical role in controlling the SHBG promoter. Interestingly, diminishing hepatic lipogenesis and free fatty acid liver biosynthesis also appear to be associated with the positive effects of thyroid hormones and PPARγ antagonists on SHBG expression. This mechanism provides a biological explanation for why SHBG is a sensitive biomarker of insulin resistance and the metabolic syndrome, and why low plasma SHBG levels are a risk factor for developing hyperglycemia and type 2 diabetes, especially in women. These important advances in our knowledge of the regulation of SHBG expression in the liver open new approaches for identifying and preventing metabolic disorder-associated diseases early in life.
| Original language | English |
|---|---|
| Pages (from-to) | 53-59 |
| Number of pages | 7 |
| Journal | Molecular and Cellular Endocrinology |
| Volume | 316 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 5 Mar 2010 |
| Externally published | Yes |
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Keywords
- Diabetes
- Fructose
- Metabolic syndrome
- Risk factor
- Sex steroid hormones
- SHBG
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology
Cite this
Sex hormone-binding globulin gene expression in the liver : Drugs and the metabolic syndrome. / Pugeat, Michel; Nader, Nancy; Hogeveen, Kevin; Raverot, Gérald; Déchaud, Henri; Grenot, Catherine.
In: Molecular and Cellular Endocrinology, Vol. 316, No. 1, 05.03.2010, p. 53-59.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Sex hormone-binding globulin gene expression in the liver
T2 - Drugs and the metabolic syndrome
AU - Pugeat, Michel
AU - Nader, Nancy
AU - Hogeveen, Kevin
AU - Raverot, Gérald
AU - Déchaud, Henri
AU - Grenot, Catherine
PY - 2010/3/5
Y1 - 2010/3/5
N2 - Sex hormone-binding globulin (SHBG) is the main transport binding protein for sex steroid hormones in plasma and regulates their accessibility to target cells. Plasma SHBG is secreted by the liver under the control of hormones and nutritional factors. In the human hepatoma cell line (HepG2), thyroid and estrogenic hormones, and a variety of drugs including the antioestrogen tamoxifen, the phytoestrogen, genistein and mitotane (Op′DDD) increase SHBG production and SHBG gene promoter activity. In contrast, monosaccharides (glucose or fructose) effectively decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4α levels, a transcription factor that play a critical role in controlling the SHBG promoter. Interestingly, diminishing hepatic lipogenesis and free fatty acid liver biosynthesis also appear to be associated with the positive effects of thyroid hormones and PPARγ antagonists on SHBG expression. This mechanism provides a biological explanation for why SHBG is a sensitive biomarker of insulin resistance and the metabolic syndrome, and why low plasma SHBG levels are a risk factor for developing hyperglycemia and type 2 diabetes, especially in women. These important advances in our knowledge of the regulation of SHBG expression in the liver open new approaches for identifying and preventing metabolic disorder-associated diseases early in life.
AB - Sex hormone-binding globulin (SHBG) is the main transport binding protein for sex steroid hormones in plasma and regulates their accessibility to target cells. Plasma SHBG is secreted by the liver under the control of hormones and nutritional factors. In the human hepatoma cell line (HepG2), thyroid and estrogenic hormones, and a variety of drugs including the antioestrogen tamoxifen, the phytoestrogen, genistein and mitotane (Op′DDD) increase SHBG production and SHBG gene promoter activity. In contrast, monosaccharides (glucose or fructose) effectively decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4α levels, a transcription factor that play a critical role in controlling the SHBG promoter. Interestingly, diminishing hepatic lipogenesis and free fatty acid liver biosynthesis also appear to be associated with the positive effects of thyroid hormones and PPARγ antagonists on SHBG expression. This mechanism provides a biological explanation for why SHBG is a sensitive biomarker of insulin resistance and the metabolic syndrome, and why low plasma SHBG levels are a risk factor for developing hyperglycemia and type 2 diabetes, especially in women. These important advances in our knowledge of the regulation of SHBG expression in the liver open new approaches for identifying and preventing metabolic disorder-associated diseases early in life.
KW - Diabetes
KW - Fructose
KW - Metabolic syndrome
KW - Risk factor
KW - Sex steroid hormones
KW - SHBG
UR - http://www.scopus.com/inward/record.url?scp=72549099341&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72549099341&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2009.09.020
DO - 10.1016/j.mce.2009.09.020
M3 - Review article
VL - 316
SP - 53
EP - 59
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1
ER -