11-Ketotestosterone is a major androgen produced in porcine adrenal glands and testes

J Steroid Biochem Mol Biol. 2021 Jun:210:105847. doi: 10.1016/j.jsbmb.2021.105847. Epub 2021 Feb 17.

Abstract

Porcine steroid hormone profiles have some unique characteristics. We previously studied human and murine steroidogenesis using steroidogenic cells-derived from mesenchymal stem cells (MSCs). To investigate porcine steroidogenesis, we induced steroidogenic cells from porcine subcutaneous preadipocytes (PSPA cells), which originate from MSCs. Using cAMP, adenovirus-mediated introduction of steroidogenic factor-1 (SF-1)/adrenal 4-binding protein (Ad4BP) induced the differentiation of PSPA cells into sex steroid-producing cells. Introducing SF-1/Ad4BP also induced the aldo-keto reductase 1C1 (AKR1C1) gene. Porcine AKR1C1 had 17β-hydroxysteroid dehydrogenase activity, which converts androstenedione and 11-ketoandrostenedione into testosterone (T) and 11-ketotestosteorne (11KT). Furthermore, differentiated cells expressed hydroxysteroid 11β-dehydrogenase 2 (HSD11B2) and produced 11KT. HSD11B2 was expressed in testicular Leydig cells and the adrenal cortex. 11KT was present in the plasma of both immature male and female pigs, with slightly higher levels in the male pigs. T levels were much higher in the male pigs. It is noteworthy that in the female pigs, the 11KT levels were >10-fold higher than the T levels. However, castration altered the 11KT and T plasma profiles in the male pigs to near those of the females. 11KT induced endothelial nitric oxide synthase (eNOS) in porcine vascular endothelial cells. These results indicate that 11KT is produced in porcine adrenal glands and testes, and may regulate cardiovascular functions through eNOS expression.

Keywords: 11KT; HSD11B2; Pig.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
  • 20-Hydroxysteroid Dehydrogenases / genetics
  • 20-Hydroxysteroid Dehydrogenases / metabolism
  • Adipocytes / cytology
  • Adrenal Glands / metabolism*
  • Androgens / metabolism*
  • Androstenedione / metabolism
  • Animals
  • Cell Line
  • Endothelial Cells / metabolism
  • Leydig Cells / metabolism
  • Male
  • Nitric Oxide Synthase Type III / genetics
  • Swine
  • Testis / metabolism*
  • Testosterone / analogs & derivatives*
  • Testosterone / metabolism

Substances

  • Androgens
  • Testosterone
  • Androstenedione
  • 20-Hydroxysteroid Dehydrogenases
  • 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Nitric Oxide Synthase Type III
  • 11-ketotestosterone