Role of 3 beta hydroxysteroid dehydrogenase (3 beta HSD) in human adrenal androgen synthesis.

Adrenarche is the maturational increase of adrenal androgens that takes pla ce in 6-8 year old children, in order to study the role of 3 beta HSD in th e regulation of the synthesis of human adrenal androgens, the abundance of 3 beta HSD mRNA (Dot Blot and semiquantitative RT-PCR) was measured in 11 h uman prepubertal and early pubertal adrenal tissues. Subjects were divided in 2 age groups (Gr): Gr1, < 8 years (y) old (n = 6, range 0.1-2.5) and Gr2 , greater than or equal to 8 y old (n = 5, range 8.0-13.0). Tissue from one adrenal tumor with Gushing's syndrome (TSC) and 2 virilizing adrenal tumor s (TV), as well as adrenal cells prepared from the TSC and from 1 TV were a lso studied. They were maintained in culture for 3 days in basal conditions (BC) and under ACTH and IGF-1 stimulation. mRNA in Gr1 was higher than in Gr2 (Dot blot: 4.65 +/- 2.70 and 0.28 +/- 0.27 AU, p = 0.006; RT-PCR: 21.5 +/- 12.5 and 6.77 +/- 3.78 AU, p = 0.039, respectively). 3 beta HSD mRNA in TSC (8.74 +/- 1.74) was higher than in the 2 TVs (0.47 +/- 0.02 and 0.87 /- 0.08) p = 0.001. in TSC cells, basal mRNA (0.82 +/- 0.10) decreased unde r ACTH (0.55 +/- 0.06), p = 0.005, and increased under IGF-1 (2.36 +/- 0.07 ), p = 0.006. No changes were observed in TV cells. On day 3, TV cells in B C secreted 1170.0 +/- 210.0 and 335.0 +/- 29.0 pmol/10(6) cells in 24 hs of DHEAS and androstenedione, while TSC cells secreted 17.1 +/- 3.5 and 73.7 +/- 11.7, respectively. Values increased under ACTH in TV cells (2006.0 +/- 360.0 and 525.0 +/- 76.0) and in TSC cells (29.8 +/- 5.4 and 366.8 +/- 129 ) p < 0.05, but they decreased under IGF-1 only in TSC cells (7.9 +/- 2.4 a nd 43.7 +/- 6.1) p < 0.05. These data support the hypothesis that human adr enarche could be secondary to a decrease of 3 beta HSD mRNA. Our finding th at when 3 beta HSD mRNA decreases androgen secretion increases (ACTH) and w hen 3 beta HSD mRNA increases androgen secretion steroidogenesis.