Nicotine affects rat Leydig cell function in vivo and vitro via down-regulating some key steroidogenic enzyme expressions

Food Chem Toxicol. 2017 Dec:110:13-24. doi: 10.1016/j.fct.2017.09.055. Epub 2017 Oct 3.

Abstract

Nicotine is consumed largely as a component of cigarettes and has a potential effect on pubertal development of Leydig cells in males. To investigate its effects, 49-day-old male Sprague Dawley rats received intraperitoneal injections of nicotine (0.5 or 1 mg/kg/day) for 2 weeks and immature Leydig cells were isolated from the testes of 35-day-old rats and treated with nicotine (0.05-50 μM). Serum hormones, Leydig cell number and related gene expression levels after in vivo treatment were determined and medium androgen levels were measured and cell cycle, apoptosis, mitochondrial membrane potential (△Ψm), and reactive oxygen species (ROS) of Leydig cells after in vitro treatment were measured. In vivo exposure to nicotine lowered serum luteinizing hormone, follicle stimulating hormone, and testosterone levels and reduced Leydig cell number and gene expression levels. Nicotine in vitro inhibited androgen production in Leydig cells by downregulating the expression levels of P450 cholesterol side cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, and steroidogenic factor 1 at different concentration ranges. In conclusion, nicotine disrupts Leydig cell steroidogenesis during puberty possibly via down-regulating some key steroidogenic enzyme expressions.

Keywords: Leydig cells; Nicotine; Steroidogenesis; Steroidogenic enzyme.

MeSH terms

  • Androgens / metabolism*
  • Animals
  • Cell Proliferation / drug effects
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism
  • Down-Regulation / drug effects
  • Follicle Stimulating Hormone / metabolism
  • Leydig Cells / cytology
  • Leydig Cells / drug effects*
  • Leydig Cells / enzymology*
  • Leydig Cells / metabolism
  • Luteinizing Hormone / metabolism
  • Male
  • Nicotine / adverse effects*
  • Rats, Sprague-Dawley
  • Steroid Isomerases / genetics
  • Steroid Isomerases / metabolism
  • Testosterone / metabolism

Substances

  • Androgens
  • Testosterone
  • Nicotine
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Cholesterol Side-Chain Cleavage Enzyme
  • Steroid Isomerases