Abstract
Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.
Highlights
The adrenal gland is a terminal effector of the hypothalamic-pituitary-adrenal axis and plays a pivotal role, predominantly via steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation [1,2,3]
We found that prenatal nicotine exposure suppressed steroidogenic acute regulatory (StAR) protein expression (p < 0.01, Figure 1A–C)
These results suggested that changes in Yin Yang 1 (YY1) expression were inversely related to changes in StAR expression
Summary
The adrenal gland is a terminal effector of the hypothalamic-pituitary-adrenal axis and plays a pivotal role, predominantly via steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation [1,2,3]. Based on the ChIP technique, we demonstrated that YY1 mediated the inhibitory function of nicotine on StAR expression in adrenal glands of fetal rats and NCI-H295A cells, and characterized the mechanisms of this inhibition in the present study. These findings provide insight into the negative regulatory mechanism of StAR expression and help explain nicotine-induced susceptibility toward adult metabolic syndrome in intrauterine growth retardation (IUGR) offspring
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
