title: Evidence for compartmentalization of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinases in rat Leydig cells using site-selective cAMP analogs.
abstract: It is generally believed that LH-stimulated steroidogenesis in Leydig cells is via activation of the cAMP second messenger system. The present study used cAMP analogs selective in their binding to the two types of cAMP-dependent protein kinase (PK-A) and/or selective in their binding to the two cAMP-binding sites on the regulatory subunits of PK-A. As the two cAMP-binding sites show positive cooperativity, synergistic increases in androgen production by rat Leydig cells occurred when they were incubated in vitro with analog pairs that selectively activated PK-A type I or II. This confirmed that both types of PK-A are present in Leydig cells and demonstrated that both PK-A types are capable of activating steroidogenesis. Synergistic increases in androgen production were also observed when either a type I selective analog (8-aminohexylamino-cAMP) or a type II selective analog (8-thiomethyl-cAMP) was paired with added cAMP. However, when these analogs were paired with LH or the adenylate cyclase activator forskolin, a synergistic increase in steroidogenesis occurred only with the type I selective analog. These results suggest that PK-A type I is compartmentalized in Leydig cells so that it has preferential access to endogenously produced cAMP.
authors.affiliation: Department of Physiology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: W H
authors.initials: WH
authors.lastname: Moger
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D007985:Leydig Cells / Q000201:enzymology*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007986:Luteinizing Hormone; D000242:Cyclic AMP; D011494:Protein Kinases