Signal transduction in the Sertoli cell: serum modulation of the response to FSH

Immature Sertoli cells of the testicular seminiferous tubule maintain the expression of their differentiated phenotype when cultured in unsupplemented medium. In preliminary experiments we observed that foetal bovine serum (FBS) stimulates polyphosphoinositides (PI) hydrolysis in Sertoli cells. We then evaluated the effect of serum on the function of the immature Sertoli cell in culture, in terms of cAMP and estrogen production. Treatment of Sertoli cells for 30 min with 1-10% FBS had no effect on basal cAMP accumulation but abolished the response to FSH. The serum concentration producing half-maximal inhibition of the FSH-dependent cAMP accumulation was 0.5-1%. Comparison of the FSH-dose-response in the absence or presence of serum showed a decreased maximal response when serum was present. Sertoli cells exposed to serum were also less responsive to the beta-adrenergic agonist isoproterenol, to cholera toxin, and to forskolin. The serum inhibition was rapidly reversed upon removal of serum or incubating the cells with the phosphodiesterase inhibitor MIX (methyl-isobutyl-xanthine). Similarly to what observed with cAMP, serum affected androgen aromatization stimulated by FSH, isoproterenol, cholera toxin, forskolin and dibutyryl cAMP. These data indicate that factors present in serum can act as modulators of the Sertoli cell function in vitro by rapidly and reversibly inhibiting the cAMP and steroidogenic response of the Sertoli cell to FSH.