English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Plasma SHBG production by the liver is influenced by its metabolic state, and hepatocyte nuclear factor-4α regulates SHBG expression in response to changes in lipogenesis. Peroxisome-proliferator receptors (PPARs) also regulate glucose homeostasis and fatty acid metabolism. The human SHBG promoter contains a PPAR-response element (PPAR-RE), and plasma SHBG levels increase in polycystic ovarian syndrome patients treated with the PPARγ agonist, rosiglitazone. In addition, plasma SHBG levels are associated with a genetic polymorphism in the PPARγ-2 coding sequence that alters its transcriptional activity. Therefore, we set out to determine whether PPARγ influences hepatic production of SHBG by using human HepG2 hepatoblastoma cells as an in vitro model. Surprisingly, treatment of HepG2 cells with rosiglitazone reduced SHBG production and SHBG promoter activity (as assessed in a luciferase reporter gene assay) by 20–25%, whereas the PPARγ antagonist, GW9662, increased both by 2- to 3-fold. The effects of PPARγ agonists and antagonists on SHBG promoter activity were substantially diminished when the PPAR-RE in the SHBG promoter was mutated. A PPARγ small interfering RNA also increased SHBG production by HepG2 cells as well as SHBG promoter activity, and the latter was accentuated by cotreatment with GW9662. Importantly, overexpression of a PPARγ-2 Pro12 variant in HepG2 cells was more effective at reducing SHBG promoter activity, when compared with PPARγ-2 Ala12, consistent with its superior PPAR-RE binding activity. We conclude that PPARγ represses human SHBG expression in liver cells, and that differences in PPARγ levels and activity contribute directly to variations in plasma SHBG levels.

Peroxisome-Proliferator Receptor γ Represses Hepatic Sex Hormone-Binding Globulin Expression