title: Effects of steroidogenesis inducing protein (SIP) on steroid production in MA-10 mouse Leydig tumor cells: utilization of a non-cAMP second messenger pathway.
abstract: We have investigated the effects of steroidogenesis inducing protein (SIP) (Endocrinology (1990) 126, 3043-3052) on steroid production in MA-10 mouse Leydig tumor cells. Our results indicate that SIP results in the stimulation of progesterone production in MA-10 cells to the same extent obtained when maximal doses of luteinizing hormone (LH), human chorionic gonadotropin (hCG) and dibutyryl cAMP (dbcAMP) are used. It was also observed that the increased progesterone production in response to SIP was not accompanied by an increase in intracellular cAMP levels as was seen following hCG stimulation. In addition, stimulation of progesterone production using maximal doses of LH, hCG and dbcAMP could be further increased by the addition of SIP to the incubation medium also indicating that this steroidogenic activity was acting through a differential signal transducing system than these hormones. That SIP was not acting through the cAMP second messenger pathway was also demonstrated by its lack of sensitivity to the neutralizing effects of a monoclonal antibody to LH as well as by its insensitivity to the protein kinase A inhibitor HA 1004 while both of these treatments significantly decreased LH and hCG stimulated steroid production. Lastly, SIP was unable to elicit the induction of several mitochondrial proteins which have previously been shown to be synthesized in MA-10 cells in response to LH, hCG and dbcAMP. Our results indicate that SIP stimulates the production of high levels of steroids through a signal transduction pathway which is distinct from that employed by trophic hormone stimulation in Leydig cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Texas Tech University Health Sciences Center, Lubbock.
authors.forename: D M
authors.initials: DM
authors.lastname: Stocco
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors; D011506:Proteins / Q000494:pharmacology*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
chemical_list: D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011506:Proteins; D013449:Sulfonamides; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D003513:Cycloheximide; D000242:Cyclic AMP