Progressive increase in non-sex-hormone-binding globulin-bound testosterone from infancy to late prepuberty in boys

Recent evidence suggests that human albumin-bound testosterone (HSA-bound T), the major constituent of nonsex hormone-binding globulin-bound T (non-SHBG-bound T), is biologically important. To examine the potential exposure of peripheral tissues to T in normal prepubertal boys, we determined the distribution of serum T into SHBG-bound, HSA-bound, non-SHBG-bound, and free fractions in 80 normal males, aged 0.5-14 yr, all at Tanner stage I of sexual development. A model assuming equilibrium between free T and T bound to 2-binding proteins (HSA and SHBG) was used. A computer program, using as constants the SHBG-T and HSA-T affinity constants and the serum HSA concentration and as variables the serum SHBG and total T concentrations, was used to calculate SHBG-bound T, HSA-bound T, non-SHBG-bound T, and free T. Serum total T increased 2.6-fold from 0.5 to 14 yr, whereas non-SHBG-bound T, HSA-bound T, and free T increased 8- to 9-fold during the same period. On the other hand, SHBG-bound T increased only 1.9-fold. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6% to 30.4%, the relative increment being greater for HSA-bound than for free T. We conclude that with advancing age, there is a progressive increase in the exposure of all tissues to T in normal prepubertal boys. At the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.