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Identification and Developmental Changes of Aromatase and Estrogen Receptor Expression in Prepubertal and Pubertal Human Adrenal Tissues

Molecular Biology Laboratory (M.S.B., N.S., E.B., C.P., J.G., M.A.R., A.B.), Endocrinology Department, Garrahan Pediatric Hospital, Buenos Aires, Argentina C1245AAM; and Centro de Investigaciones Oncológicas (M.B., E.L.), Centro de Investigaciones Oncológicas, Fundación para la Investigación y Prevención del Cancer, Buenos Aires, Argentina C1426ANZ

Address all correspondence and requests for reprints to: Alicia Belgorosky, Endocrinology Service, Hospital de Pediatria Garrahan, C. de los Pozos 1881, Buenos Aires, Argentina C1245AAM. E-mail: abelgo{at}elsitio.net.

Context: The mechanisms of postnatal adrenal zonation remain unclear.

Objective: To provide a clue for a possible role of estrogens in adrenarche, we studied the expression of estrogen receptor (ER), ERß, G protein-coupled receptor (GPR)30, and cP450aromatase (cP450arom) in human adrenal tissue.

Design: Human adrenal tissue was collected from three postnatal age groups (Grs): Gr 1, younger than 3 months (n = 12), fetal zone involution; Gr 2, 3 months to 6 yr (n = 17), pre-adrenarche; and Gr 3, older than 6–20 yr (n = 12), post-adrenarche period.

Results: ERß mRNA in Grs 1 and 3 was higher than in Gr 2 (P < 0.05). By immunohistochemistry and laser capture microdissection followed by RT-PCR, ERß was expressed in zona reticularis and fetal zone, GPR30 in zona glomerulosa (ZG) and adrenal medulla, while ER mRNA and protein were undetectable. cP450arom mRNA in Gr 3 was higher than in Grs 1 and 2 (P < 0.05), and localized to ZG and adrenal medulla by laser capture microdissection. cP450arom Immunoreactivity was observed in adrenal medulla in the three Grs and in subcapsular ZG of Gr 3. Double-immunofluorescence studies revealed that cP450arom and chromogranin A only colocalize in adrenal medulla of subjects younger than 18 months. In these samples, exon 1.b-derived transcript was 3.5-fold higher, while exon 1.a-, 1.c-, and 1.d-derived transcripts were 3.3-, 1.9-, and 1.7-fold lower, respectively, than in subjects older than 6 yr.

Conclusions: Our results suggest that estrogens produced locally in adrenal medulla would play a role in zona reticularis functional differentiation through ERß. The cP450arom and GPR30 expression in subcapsular ZG, colocalizing with a high-cell proliferation index, previously reported, suggests a local GPR30-dependent estrogen action in proliferation and migration of progenitor adrenal cells.

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