Flutamide treatment reveals a relationship between steroidogenic activity of Leydig cells and ultrastructure of their mitochondria

Sci Rep. 2021 Jul 2;11(1):13772. doi: 10.1038/s41598-021-93292-8.

Abstract

Our present knowledge on interrelation between morphology/ultrastructure of mitochondria of the Leydig cell and its steroidogenic function is far from satisfactory and needs additional studies. Here, we analyzed the effects of blockade of androgen receptor, triggered by exposure to flutamide, on the expression of steroidogenic proteins (1) and ultrastructure of Leydig cells' constituents (2). We demonstrated that increase in the expression level of steroidogenic (StAR, CYP11A1, 3β-HSD, and CYP19A1) proteins (and respective mRNAs) in rat testicular tissue as well as elevation of intratesticular sex steroid hormone (testosterone and estradiol) levels observed in treated animals correspond well to morphological alterations of the Leydig cell ultrastructure. Most importantly, up-regulation of steroidogenic proteins' expression apparently correlates with considerable multiplication of Leydig cell mitochondria and subsequent formation of local mitochondrial networks. Interestingly, we showed also that the above-mentioned processes were associated with elevated transcription of Drp1 and Mfn2 genes, encoding proteins implicated in mitochondrial dynamics. Collectively, our studies emphasize the importance of mitochondrial homeostasis to the steroidogenic function of Leydig cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatase / genetics*
  • Cholesterol Side-Chain Cleavage Enzyme / genetics*
  • Flutamide / pharmacology
  • Gene Expression Regulation, Developmental
  • Gonadal Steroid Hormones / biosynthesis
  • Gonadal Steroid Hormones / genetics
  • Hydroxysteroid Dehydrogenases / genetics*
  • Leydig Cells / drug effects
  • Leydig Cells / metabolism
  • Luteinizing Hormone / biosynthesis
  • Luteinizing Hormone / metabolism
  • Male
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / ultrastructure
  • Rats
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Steroids / biosynthesis
  • Steroids / metabolism
  • Testis / growth & development
  • Testis / metabolism
  • Testosterone / biosynthesis
  • Testosterone / metabolism

Substances

  • Gonadal Steroid Hormones
  • Receptors, Androgen
  • Steroids
  • Testosterone
  • Flutamide
  • Luteinizing Hormone
  • Hydroxysteroid Dehydrogenases
  • Aromatase
  • CYP19A1 protein, rat
  • Cholesterol Side-Chain Cleavage Enzyme