Sodium chlorate induces undersulfation of cellular proteoglycans and increases in FSH-stimulated estradiol production in immature rat Sertoli cells

The functional influence of cell proteoglycan (PG) undersulfation on estrad iol synthesis by immature rat Sertoli cell cultures was investigated by usi ng sodium chlorate, an inhibitor of the active sulfate donor for sulfotrans ferases. The addition of sodium chlorate to 20-day-old rat Sertoli cell cul tures abolished [S-35]-sulfate incorporation into neosynthesized PG and con sequently reduced the residence time of undersulfated PG in cell membrane. Simultaneously. follicle-stimulating hormone (FSH)-stimulated estradiol syn thesis was increased by 45%. The effects of sodium chlorate upon Sertoli ce ll PG synthesis and steroidogenesis were not reproduced with the addition o f sodium chloride. Addition of phosphodiesterase inhibitors (MIX or Ro20-17 24) decreased the magnitude of the chlorate effect on FSH-stimulated steroi dogenesis, suggesting that part of chlorate's effect on steroidogenesis res ulted from a decrease in adenosine cyclic 3',5'-phosphate (cAMP)-specific p hosphodiesterase activity. Additionally, chlorate 1) increased Sertoli cell steroidogenesis at a step located beyond cAMP (restricted to Sertoli cell cultures exhibiting moderate steroidogenic response to (Bu)(2)cAMP) and 2) abolished the inhibition of steroidogenesis induced by transforming growth factor-beta. These results support our previous data. which showed that alt eration in PG synthesis and the consequent decrease in cell membrane PG con tent induce an increase in FSH-stimulated estradiol synthesis in Sertoli ce ll cultures. The identification of cAMP-specific phosphodiesterase activity as a signal transduction step modified by PG undersulfation suggests the p ossible involvement of cell PG in the regulation of phosphodiesterase activ ity and, therefore, of FSH responsiveness during testicular development.