Effects of di(n-butyl) and monobutyl phthalate on steroidogenesis pathways in the murine Leydig tumor cell line MLTC-1

Environ Toxicol Pharmacol. 2013 Sep;36(2):332-338. doi: 10.1016/j.etap.2013.04.013. Epub 2013 May 6.

Abstract

Di(n-butyl) phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) have been shown to disrupt reproductive organ growth. The objective of this study was to evaluate the effects of DBP/MBP on steroidogenesis in the murine Leydig tumor cell line MLTC-1 in vitro. MLTC-1 cells were incubated with various concentrations of DBP (100, 1, 0.01, and 0μmol/l in DMSO) and MBP (1000, 10, 0.1, and 0μmol/l in DMSO) for 24h. Testosterone secretion was stimulated at the lowest doses and inhibited at higher treatment doses of DBP and MBP. The mRNA levels of the side-chain cleavage enzyme (P450scc), cytochrome p450c17 (P450c17) and 3β-hydroxy-steroid dehydrogenase (3βHSD) were significantly reduced in the phthalate-exposed groups, whereas, the transcription and translation of insulin-like hormone 3 (INSL3) was affected by DBP and MBP. Alterations of the steroidogenic enzymes and INSL3 in MLTC-1 cells may be involved in the biphasic effects of DBP/MBP on androgen production.

Keywords: 3β-Hydroxysteroid dehydrogenase; Di(n-butyl) phthalate; Insulin-like hormone 3; Monobutyl phthalate; P450 side-chain cleavage enzyme; Testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / genetics
  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism
  • Dibutyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Insulin / genetics
  • Insulin / metabolism
  • Leydig Cell Tumor / genetics
  • Leydig Cell Tumor / metabolism*
  • Leydig Cell Tumor / pathology
  • Male
  • Mice
  • Phthalic Acids / toxicity*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / metabolism
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism*
  • Testicular Neoplasms / pathology
  • Testosterone / biosynthesis*
  • Time Factors

Substances

  • Insulin
  • Leydig insulin-like protein
  • Phthalic Acids
  • Proteins
  • RNA, Messenger
  • Dibutyl Phthalate
  • Testosterone
  • 3-Hydroxysteroid Dehydrogenases
  • Cholesterol Side-Chain Cleavage Enzyme
  • monobutyl phthalate