Changes in the free (unbound) fraction of testosterone in serum in vitro as affected by pH and temperature.

Concomitant effects of temperature and pH on changes in the magnitude of the free, unbound fraction of testosterone in human serum were studied. Free fraction was determined by equilibrium dialysis of undiluted serum against buffer in microchambers at temperatures ranging from 36 to 39 degrees C and pH ranging from 6.9 to 7.4. Free fraction increased with increasing temperature and decreasing pH, the two factors acting synergically. This is reflected by the fact that a rise in temperature from 36 to 39 degrees C causes only a slight increase in the free fraction at pH = 7.4 (about 7%), while at pH = 6.9 that increase is about 35%. At 39 degrees C and pH = 6.9 the free fraction was about 1.5-fold higher than in standard conditions (37 degrees C, pH = 7.4). This implies that in vivo the free, biologically active fraction of testosterone may increase due to e.g. hyperthermia and acidosis at a constant total concentration of this hormone.