ADRENARCHE RESULTS FROM DEVELOPMENT OF A 3-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENT ADRENAL RETICULARIS

Adrenarche is the increased adrenal production of dehydroepiandrostero ne (DHEA) and dehydroepiandrosterone sulfate (DHEAS) that occurs durin g the prepubertal period. To date, the exact mechanism initiating adre narche is unknown, although many factors have been postulated. In the present study, we examined the hypothesis that alterations in intra-ad renal expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) o r 21-hydroxylase (CYP21) within the inner reticularis zone leads to th e increased production of 19-carbon (C-19) steroids. After conversion of cholesterol to pregnenolone, 17 alpha-hydroxylase/17,20-lyase (CYP1 7) can metabolize pregnenolone through to DHEA. The enzyme 3 beta HSD competes for substrate with CYP17 and effectively removes steroid prec ursor from the pathway leading to DHEA. On the other hand, deficiency in CYP21 expression is known to cause excessive production of adrenal C-19 steroids, suggesting that CYP21 could play a role in adrenarche. Thus, a decrease in 3 beta HSD or CYP21 expression would allow substra te to flow toward the synthesis of DHEA. To determine whether adrenarc he results from a decreased expression of 3 beta HSD or CYP21 in the r eticularis, immunohistochemical localization of 3 beta HSD and CYP21 w as performed, and staining intensities compared using adrenal glands f rom children ages 4 months to 4 yr (n = 12), ages 5-7 yr (n = 9), ages 8-13 yr (n = 9), and adults ages 25-56 yr (n = 8). There were no diff erences in the zonal expression of CYP21. No difference in 3 beta HSD staining was observed between the glomerulosa and fasciculata from any age group. However, children age 8 yr and older show a significant de crease in 3 beta HSD expression in reticularis as compared with the fa sciculata. No significant difference was noted for 3 beta HSD levels b etween the fasciculata and reticularis for children age 7 yr or younge r. The level of 3 beta HSD expression in the reticularis continued to decrease in the adult adrenals examined. These findings suggest that a s children mature there is a decreased level of 3 beta HSD in the adre nal reticularis that may contribute to the increased production of DHE A and DHEAS seen during adrenarche.