Abstract 21

Adrenarche is the increased of adrenal androgen secretion, mainly DHEA sulfate (DS), that occurs during prepuberty in higher primates. This event takes place at about 6-8 years (y) of age in humans. It had been postulated that adrenarche might reflect an increase in the ratio 17,20- lyase: 17OH ase activity of P450c17. However, studies to demonstrate this mechanism have been unsuccessful. Since it has been described that virilized adrenal cortical carcinomas have high DS secretion and low 3βHSD activity, in this study we evaluated the possible existence of madurative changes of the expression of 3βHSD mRNA and of the ratio between 3βHSD and P450c21 mRNA in 11 normal human prepubertal adrenal tissues. Adrenal glands from subjects aged 0.1 to 13 y were obtained from organ donors, patients undergoing resection of the kidney for renal neoplasms or necropsies with less than 6 hours of post mortem time. The expression of 3βHSD and P450c21mRNA were studied by Dot Blot in all samples, while Nothern Blot analysis was carried out only in 3 of them because of scarce availability of tissue. Hybridization was performed using label human 3βHSD and P450c21 cDNA probes. The uniformity of loading was tested using a βactin probe. The relative intensities of hybridization signals were quantified by scanning densitometry. For the analysis of the results, subjects were divided in two groups (Gr), as a function of age. GR1: less than 8y (n=6) range; 0-1-2.48y, and Gr2: equal or older than 8y (n=5) range; 8-13y. 3βHSD mRNA expression was significantly higher in Gr1 than in Gr2 (4.65±2.7 and 0.28±0.27 arbitrary units, respectively, p=0.006). A significant negative correlation of 3βHSD mRNA expression and of P450c21 mRNA expression, as a function of age, was found (r: -0.749. p=0.008 and r=0.764, p=0.01, respectively). However, P450c21: 3βHSD mRNA ratio was significantly lower in Gr1 than in Gr2 (0.84±0.65 and 3.07±1.07, respectively, p=0.003). In conclusion, we have shown, for the first time, a decrement of the expression of 3βHSD as a function of age in prepubertal normal human adrenal tissue. This madurative change might be involved in the mechanism of human adrenarche.