Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-celi adenylate cyclase

The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2 h. Forskolin also potentiated the action ofLH on cyclicAMP production, but was only additive with cholera toxin. Preincubation ofrat Leydig tumour cells with LH (1.0pg/ml) for 1 h produced a desensitization of the subsequent LH (1.Opg/ml)-stimulated cyclic AMP production, whereas the responses to cholera toxin (5.0ug/ml), forskolin (100pM), LH plus forskolin or cholera toxin plus forskolin were unaltered. In contrast, preincubation with LH for 20h produced a desensitization to all the stimuli tested. When rat Leydig tumour cells were preincubated for 1 h with forskolin or dibutyryl cyclic AMP, the only subsequent response that was significantly altered was that to LH plus forskolin after preincubation with forskolin. However, preincubation for 20h with forskolin or dibutyryl cyclic AMP induced a desensitization to all stimuli subsequently tested. LH produced a rapid (0-1 h) homologous desensitization, which was followed by a slower (2-8h)-onset heterologous desensitization. Forskolin and dibutyryl cyclic AMP were only able to induce heterologous desensitization. The rate of desensitization induced by either forskolin