A comparative study of the action of several lutropin derivatives on rat Leydig cells.
Rat intestinal cells prepared from testes were incubated in the presence of different lutropin derivatives obtained by chemical modification of the amino groups. The cAMP accumulation and the testosterone biosynthesis were determined in the cell homogenates. Binding determinations were carried out by a radioligand receptor assay using tritiated methylated lutropin. The binding activities--relative to native LH--of three different derivatives obtained by reductive alkylation (methylated, ethylated and isopropylated LH) were in good agreement with the relative potencies assessed by their capacity to stimulate cAMP and testosterone production. Guanidinated LH (11-NH2 groups modified) exhibited a binding activity and a relative potency relatively high with regard to cAMP accumulation (as compared with that of native LH). Its steroidogenic potency, however, was very low. When Leydig cells were incubated in the presence of native and guanidinated LH, the testosterone production was similar to that induced by the derivative alone, indicating that the derivative exerted a competitive inhibitory action preventing the stimulation of steroidogenesis by native LH. These results suggest that a guanidinated derivative is able to bind to the LH receptor and the complex so formed is able to be coupled with an adenylate cyclase pool (or cAMP compartment) which is not connected with the steroidogenic pathway.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D007985:Leydig Cells / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D011869:Radioligand Assay; D051381:Rats; D011956:Receptors, Cell Surface; D013739:Testosterone / Q000096:biosynthesis*
D011956:Receptors, Cell Surface; D013739:Testosterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP