title: The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway.
abstract: CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily. It is expressed at high levels in adipose tissue and has recently emerged as a novel adipokine. In the present study, we provide the first evidence for a physiological role of the new adipokine, CTRP3, in the reproductive system. CTRP3 was specifically expressed in interstitial Leydig cells, where testosterone is produced, in the adult mouse testis. CTRP3 increased testosterone production by TM3 mouse Leydig cells in a dose-dependent manner. The increased testosterone production was linked to upregulation of steroidogenic proteins expression, such as steroidogenic acute regulatory (StAR) protein and cholesterol side-chain cleavage cytochrome P450 (P450scc). Moreover, increases in intracellular cyclic AMP (cAMP) concentrations and the phosphorylation of cAMP-response element binding protein (CREB) in CTRP3-stimulated TM3 Leydig cells were observed. Inhibition of this signaling pathway by a specific protein kinase A (PKA) inhibitor, H89, blocked testosterone production in CTRP3-stimulated Leydig cells, suggesting that the stimulatory effect of CTRP3 on testosterone production is associated with activation of the cAMP/PKA signaling pathway. Thus, our results demonstrate a physiological role for CTRP3 in testicular steroidogenesis and provide novel insights in the intracellular mechanisms activated by this protein.
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Otani
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kogo
authors.forename: Souhei
authors.initials: S
authors.lastname: Furukawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakisaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Maeda
mesh_terms: D054392:Adipokines; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D017931:DNA Primers; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: D054392:Adipokines; C428135:CORS26 protein, mouse; D017931:DNA Primers; D011506:Proteins; D013739:Testosterone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases