Action of nitroguanidinated luteinizing hormone on different rat gonadal tissues.
The biological activities of nitroguanidinated derivatives prepared from ovine or porcine luteinizing hormone were investigated using rat Leydig cells and pseudopregnant rat ovaries. In these tissues nitroguanidyl ovine luteinizing hormone (NGoLH) or nitroguanidyl porcine luteinizing hormone (NGpLH) were unable to stimulate adenylate cyclase or steroidogenesis but were able to inhibit the binding of ovine or porcine native LH to their specific receptors. When added to incubations of isolated Leydig cells or pseudopregnant ovary slices, NGoLH as well as NGpLH inhibited the stimulating action of native LH on adenylate cyclase or steroidogenesis. However, these derivatives had no inhibiting action on the stimulation of adenylate cyclase and steroidogenesis induced in the Leydig cells by choleratoxin or on the stimulation of testosterone production induced by 8-bromo-cyclic AMP. Since NGpLH (which does not contain lysine residues or free alpha-amino groups in the beta-subunit) exhibits the same antagonist action as NGoLH, we conclude that the nitroguanidination of the alpha-subunit is sufficient to endow the derivative with antihormone properties.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007985:Leydig Cells / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D010053:Ovary / Q000187:drug effects*; D011374:Progesterone / Q000096:biosynthesis; D011555:Pseudopregnancy / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep; D013552:Swine; D013739:Testosterone / Q000096:biosynthesis
C024424:luteinizing hormone, nitroguanidyl; D013739:Testosterone; D011374:Progesterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases