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.