Redox regulation of hormone sensitive lipase: Potential role in the mechanism of MEHP-induced stimulation of basal steroid synthesis in MA-10 Leydig cells

Authors

Christine Zhou, Department of Biochemistry and Genetics, Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, NC 27546, USA.
Ninad Zaman, Department of Biochemistry and Genetics, Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, NC 27546, USA.
Y R. Li, Department of Pharmacology, Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, NC 27546, USA.
Daniel B. Martinez-Arguelles, Research Institute of the McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec H4A 3J1, Canada.
Vassilios Papadopoulos, Deparment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Barry Zirkin, Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Kassim Traore, Department of Biochemistry and Genetics, Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, NC 27546, USA. Electronic address: ktraore@campbell.edu.

Document Type

Article

Date of Publication

4-1-2019

Publication Title

Reproductive toxicology (Elmsford, N.Y.)

First Page

19

Last Page

25

Abstract

Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a plasticizer with endocrine disruptor activity that has been shown to stimulate basal steroid biosynthesis in Leydig cells. The mechanism by which it does so is unknown. Using MA-10 mouse tumor Leydig cells, we assessed the effects of MEHP on reactive oxygen species (ROS) levels, and on the signal transduction pathways that mobilize cholesterol. Exposure to 0-300 μM MEHP stimulated basal progesterone production in a dose-dependent manner. Progesterone stimulation was correlated with increases in the phosphorylation of hormone-sensitive lipase (HSL; aka cholesteryl ester hydrolase), which is involved in the production of free cholesterol, and of steroidogenic acute regulatory (STAR) protein expression. Co-treating MA-10 cells with MEHP and the ROS scavenger N-acetyl cysteine (NAC) blocked the activation of HSL, blunted MEHP-induced STAR, and reduced basal progesterone formation. These observations suggest that ROS generation by MEHP leads to activation of HSL and increase in STAR which, together, result in increased free-cholesterol bioavailability and progesterone formation.

DOI

10.1016/j.reprotox.2018.12.010

Recommended Citation

Zhou, Christine; Zaman, Ninad; Li, Y R.; Martinez-Arguelles, Daniel B.; Papadopoulos, Vassilios; Zirkin, Barry; and Traore, Kassim, "Redox regulation of hormone sensitive lipase: Potential role in the mechanism of MEHP-induced stimulation of basal steroid synthesis in MA-10 Leydig cells" (2019). Osteopathic Medicine, Jerry M. Wallace School of. 2397.
https://cufind.campbell.edu/medicine_school/2397