A novel function of geranylgeraniol in regulating testosterone production

Biosci Biotechnol Biochem. 2018 Jun;82(6):956-962. doi: 10.1080/09168451.2017.1415129. Epub 2018 Jan 5.


Isoprenoids play widely differing roles in various physiological processes in animals and plants. Geranylgeraniol (GGOH) is an isoprenoid found in plants, and is an important metabolic derivative in the isoprenoid/cholesterol synthesis pathway. Earlier studies focused on GGOH's ability to improve the side effects of bisphosphonate therapy by regulating the mevalonate pathway. More recently, the mevalonate pathway-independent effects of GGOH have been described, including anti-inflammatory, anti-tumorigenic, and neuroprotective activities. It is noteworthy that GGOH regulates the steroidogenesis pathway in testis-derived I-10 tumor cells. Testosterone is a hormone produced via steroidogenesis in testicles and plays a role in fetal development and the male reproductive system. GGOH enhanced testosterone and progesterone (its precursor) levels in I-10 cells by activating adenylate cyclase via cAMP/PKA signaling, without altering phosphodiesterase activity. These findings highlight the potential benefits of GGOH as a therapeutic agent for low testosterone levels, such as late-onset hypogonadism in men.

Keywords: AC: adenylate cyclase; FOH: farnesol; GGOH: geranylgeraniol; GGPP: geranylgeranyl diphosphate; GOH: geraniol; Geranylgeraniol; IBMX: 3-isobutyl-1-methylxanthine; MDL: MDL-12,330A; PDE: phosphodiesterase; PKA: protein kinase A; StAR: steroidogenic acute regulatory protein; cAMP/PKA; progesterone; steroidogenesis; testosterone.

Publication types

  • Review

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism
  • Animals
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dietary Supplements
  • Diterpenes / pharmacology*
  • Humans
  • Leydig Cells / cytology
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Male
  • Mevalonic Acid / metabolism
  • Progesterone / biosynthesis
  • Signal Transduction
  • Terpenes / pharmacology
  • Testosterone / biosynthesis*
  • Testosterone / blood
  • Testosterone / metabolism


  • Diterpenes
  • Terpenes
  • Testosterone
  • Progesterone
  • geranylgeraniol
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases
  • Mevalonic Acid