LACK OF CORRELATION BETWEEN SEX-HORMONE BINDING GLOBULIN, ADRENAL AND PERIPHERAL ANDROGENS IN PRECOCIOUS ADRENARCHE

Sex hormone binding globulin (SHBG) is a specific steroid-binding plasma glycoprotein regulated by several different factors. Sex steroids are currently considered to be the main physiological regulators of this protein. Testosterone (T) in adults seems to be the main hormone active in lowering SHBG. The role of dihydrotestosterone (DHT) in such regulation, particularly in the prepubertal age, is not well understood, and no data exist about the role of 3-alpha-androstanediol (3A-alpha) and its glucuronide. In adulthood, in addition to T, 5-ene steroids seems to play a role in the regulation of SHBG plasma concentration. To assess the effect of adrenal and peripheral androgens in modulating SHBG levels in the prepubertal age, we studied subjects with precocious pubarche secondary to precocious adrenarche (PA). PA represents, in fact, a good model of study as it is characterized by an increased production and action of adrenal androgen in females under 8 yr of age and in males under 9. Sixty-five subjects (55 females and 10 males; chronologic age: 3.6 - 8.2 yr (6.9+/-1.3, SD); bone age: 3.6 - 11 yr (7.6+/-1.9); BMI 17.9+/-3 kg/m2) were studied. Fifteen age-matched normal children (BMI 15.2+/-0.8 kg/m2) were studied as controls. Androstenedione (A), dehydroepiandrosterone (DHA) and its sulphate (DHA-S), T, DHT, 3Ad and its glucuronide (3AG) and SHBG were evaluated in all subjects. In PA cases serum SHBG levels (50+/-27 nM) were significantly lower (p<0.05) with respect to normal prepubertal patients. Glandular androgens, as expected, were significantly higher with respect to controls (p<0.001 for A and DHA; p<0.02 for T; p<0.05 for DHA-S). Peripheral androgens were also significantly higher in PA patients (p<0.001 for DHT and 3Ad; p<0.01 for 3AG). No correlation was found between SHBG and steroids, whereas SHBG correlated inversely with BA (p<0.01) and with BMI (p<0.02). In conclusion, our results in PA i) confirm previous observations about the lack of correlation between SHBG and adrenal steroids, ii) point out the lack of correlation between SHBG and peripheral androgens, iii) led to the conclusion that other factors, such as nutritional state and growth can be considered as playing a major role in regulating SHBG levels in the prepubertal age.