Testosterone Modulates K⁺ _ATP Channels in Sertoli Cell Membrane via the PLC-PIP₂ Pathway

Abstract

Testosterone at physiological intratesticular concentrations induces a dose-dependent depolarisation and an increase in input resistance together with an increment of ⁴⁵Ca²⁺ uptake in the Sertoli cells from seminiferous tubules of immature rat. Previous studies have implicated K⁺ _ATP channels in these testosterone actions. This study demonstrates that testosterone and sulphonylureas (glibenclamide and tolbutamide) depolarise the membrane potential, augment resistance and ⁴⁵Ca²⁺ uptake in the Sertoli cells of seminiferous tubules from 10 - 15 day-old rats. These actions were nullified by the presence of the K⁺ _ATP channel opener diazoxide. The depolarisation was also observed with the impermeant bovine serum albumin-bound testosterone. Testosterone actions were blocked by both pertussis toxin and the phospholipase C (PLC) inhibitor U73122 implying the involvement of PLC - phosphatidylinositol 4-5 bisphosphate (PIP₂) hydrolysis via G protein in testosterone actions. Polycations, including spermine and LaCl₃, depolarised the membrane potential and increased the resistance. Hyperpolarisation caused by EGTA was reversed by LaCl₃ and by the presence of testosterone. This last effect was nullified by the presence of U73122. All of the above results indicate that the action of testosterone on the Sertoli cell membrane is exercised on the K⁺ _ATP channels through PLC-PIP₂ hydrolysis that closes the channel, depolarises the membrane, and stimulates ⁴⁵Ca²⁺ uptake.

Key words

Androgens · K_IR channels · Testes · Sulphonylureas · Diazoxide · Pertussis toxin · U73122

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