title: Geranylgeraniol enhances testosterone production via the cAMP/protein kinase A pathway in testis-derived I-10 tumor cells.
abstract: Testosterone levels in men decrease with age; this decline has been linked to various diseases and can shorten life expectancy. Geranylgeraniol (GGOH) is an isoprenoid found in plants that plays an important role in several biological processes; however, its role in steroidogenesis is unknown. Here, we report that GGOH enhances the production of testosterone and its precursor progesterone in testis-derived I-10 tumor cells. GGOH induced protein kinase A (PKA) activity and increased cAMP levels and was found to regulate cAMP/PKA signaling by activating adenylate cyclase without altering phosphodiesterase activity. GGOH also stimulated mRNA and protein levels of steroidogenic acute regulatory protein, a downstream effector in the cAMP/PKA pathway. These results demonstrate that GGOH enhances steroidogenesis in testis-derived cells by modulating cAMP/PKA signaling. Our findings have potential applications for the development of therapeutics that increase testosterone levels in aging men.
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Ho
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shirakawa
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Asagi
authors.initials: A
authors.lastname: Ito
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Maeda
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Goto
authors.affiliation: a Laboratory of Nutrition , Graduate School of Agricultural Science, Tohoku University , Sendai , Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Komai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D015398:Signal Transduction; D013736:Testicular Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D004224:Diterpenes; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D011374:Progesterone; C017338:geranylgeraniol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: cAMP; geranylgeraniol; progesterone; protein kinase A; testosterone