Effects of the transmethylation inhibitor S-adenosyl-homocysteine and of the methyl donor S-adenosyl-methionine on rat Leydig cell function in vitro.
In purified rat Leydig cells, the methyl donor S-adenosyl-methionine (SAM), increases significantly in a dose dependent manner the [125I]hCG binding as well as the productions of cAMP and of testosterone; the competitive inhibitor of methylations S-adenosyl-homocysteine (SAH), has an opposite effect. Associated to oLH, SAM further enhances the cAMP synthesis while SAH inhibits significantly the adenylate cyclase activity. With regard to testosterone synthesis, SAM potentiates the stimulating roles of oLH and dbcAMP (27 and 38% increases, respectively) although SAH diminishes testosterone productions (48 and 35%, respectively under oLH and dbcAMP stimulations). Scatchard analysis has shown that SAM (1.4 mM) increases the number of LH/hCG binding sites on Leydig cells while SAH (1.4 mM) decreases it; LH/hCG Ka values are not modified neither by SAM nor by SAH. These data suggest that the in vitro regulation of steroidogenesis in purified rat Leydig cells may involve methylation processes (presumably phospholipids are the potential substrates of these reactions) which modulates the transmission of the hormonal signal through the membrane and affects the testosterone synthesis at a step beyond the adenylate cyclase.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000031:analogs & derivatives*; D007985:Leydig Cells / Q000187:drug effects / Q000502:physiology*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D008745:Methylation; D051381:Rats; D011974:Receptors, LH / Q000502:physiology; D012435:S-Adenosylhomocysteine / Q000494:pharmacology*; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013739:Testosterone / Q000096:biosynthesis
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D006710:Homocysteine; D013739:Testosterone; D003994:Bucladesine; D012436:S-Adenosylmethionine; D007986:Luteinizing Hormone; D012435:S-Adenosylhomocysteine; D000242:Cyclic AMP