β-Adrenergic regulation of Sertoli cell adenylyl cyclase: desensitization by homologous hormone

Abstract

Incubation of Sertoli cell-enriched cultures with d, l-isoproterenol caused a time- and concentration-dependent, homologous desensitization of isoproterenol-responsive adenylyl cyclase, whereas the response to FSH was unaffected. Half-maximal desensitization was achieved within l h of preincubation, after which a more gradual loss of response was observed. Preincubation of Sertoli cells for 24 h with increasing concentrations of d, l-isoproterenol demonstrated that the concentration required to obtain half-maximal desensitization was approximately 10-fold lower than the K m for activation of adenylyl cyclase. The function of the guanine nucleotide regulatory component (N-component) of the adenylyl cyclase complex in hormonally desensitized Sertoli cells, as evaluated by activation of adenylyl cyclase by GTP, GMPP(NH)P, fluoride and Mg 2+, was not affected by the hormone pretreatment. Preincubation of Sertoli cells with a high concentration of dbcAMP (10 -3 M) for 24 h was associated with a 45% reduction in adenylyl cyclase activation by both FSH and isoproterenol. Also in this case fluoride- and GTP-stimulated adenylyl cyclase activities were normal. However, the effects of dibutyryl cyclic AMP occurred much more slowly than agonist-induced desensitization, indicating that cAMP may not be the primary mediator of homologous desensitization of Sertoli cell adenylyl cyclase by isoproterenol.