Effect of glucocorticoids on androgen biosynthesis in the testes of the toad Rhinella arenarum (Amphibia, Anura)

J Exp Zool A Ecol Integr Physiol. 2019 Jan;331(1):17-26. doi: 10.1002/jez.2232. Epub 2018 Sep 15.

Abstract

In rat Leydig cells, glucocorticoids (GCs) inhibit testosterone production through the interaction with the glucocorticoid receptor (GR). However, the sensitivity of those cells to GCs is regulated by the enzyme 11β-hydroxysteroid dehydrogenase Type 1 (11β-HSD1). In the testes of the toad Rhinella arenarum, the presence of an 11β-HSD similar to type 2 and a cytosolic GR has also been described. However, there is a lack of information regarding the effects of GCs on amphibian testicular steroidogenesis. In this study, the effects of corticosterone on androgen production, and the activity of two steroidogenic enzymes in toad testes were reported. Corticosterone inhibits androgen production via the GR because the GR antagonist RU486 prevents corticosterone-induced inhibition of testosterone. Corticosterone also reduced the activity of the cytochrome P450 17-hydroxylase, C17,20-lyase (Cyp450 c17 ) without affecting the 3β-hydroxysteroid dehydrogenase/isomerase activity. This effect on Cyp450 c17 was likewise inhibited by RU486. On the other hand, corticosterone had no effect on the amount of steroidogenic acute regulator protein. These results suggest that GCs inhibit steroidogenesis in toad testes by reducing of Cyp450 c17 activity via a GR-mediated mechanism.

Keywords: amphibians; androgens; glucocorticoids (GC); steroidogenesis; testes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism*
  • Androgens / biosynthesis*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Bufonidae / metabolism*
  • Corticosterone / administration & dosage
  • Corticosterone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Gene Expression Regulation / drug effects
  • Glycyrrhetinic Acid / administration & dosage
  • Glycyrrhetinic Acid / pharmacology
  • Male
  • Mifepristone
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / metabolism*
  • Testis / drug effects*
  • Testis / metabolism
  • Tissue Culture Techniques

Substances

  • Androgens
  • Anti-Inflammatory Agents
  • Mifepristone
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Steroid 17-alpha-Hydroxylase
  • Glycyrrhetinic Acid
  • Corticosterone