| First Author | Zhang F | Year | 2018 |
| Journal | Neuroscience | Volume | 379 |
| Pages | 115-125 | PubMed ID | 29555426 |
| Mgi Jnum | J:262719 | Mgi Id | MGI:6162124 |
| Doi | 10.1016/j.neuroscience.2018.03.009 | Citation | Zhang F, et al. (2018) The Involvement of PPARs in the Selective Regulation of Brain CYP2D by Growth Hormone. Neuroscience 379:115-125 |
| abstractText | Brain CYP2D is responsible for the synthesis of endogenous neurotransmitters such as dopamine and serotonin. This study is to investigate the effects of cerebral CYP2D on mouse behavior and the mechanism whereby growth hormone regulates brain CYP2D. The inhibition of cerebellar CYP2D significantly affected the spatial learning and exploratory behavior of mice. CYP2D expression was lower in the brain in GHR-/- mice than that in WT mice; however, hepatic CYP2D levels were similar. Brain PPARalpha expression in male GHR-/- mice were markedly higher than those in WT mice, while brain PPARgamma levels were decreased or unchanged in different regions. However, both hepatic PPARalpha and PPARgamma in male GHR-/- mice were markedly higher than those in WT mice. Pulsatile GH decreased the PPARalpha mRNA level and increased the mRNA levels of CYP2D6 and PPARgamma in SH-SY5Y cells. A luciferase assay showed that PPARgamma activated the CYP2D6 gene promoter while PPARalpha inhibited its function. Pulsatile GH decreased the binding of PPARalpha to the CYP2D6 promoter by 40% and promoted the binding of PPARgamma to the CYP2D6 promoter by approximately 60%. The male GH secretory pattern altered PPAR expression and the binding of PPARs to the CYP2D promoter, leading to the elevation of brain CYP2D in a tissue-specific manner. Growth hormone may alter the learning and memory functions in patients receiving GH replacement therapy via brain CYP2D. |
