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This version published online on April 3, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2329
A more recent version of this article appeared on June 1, 2007
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Right arrow Adrenal and Hypertension
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Submitted on October 25, 2006
Accepted on March 27, 2007

IDENTIFICATION AND DEVELOPMENTAL CHANGES OF AROMATASE AND ESTROGEN RECEPTOR EXPRESSION IN PREPUBERTAL AND PUBERTAL HUMAN ADRENAL TISSUES

María Sonia Baquedano, Nora Saraco, Esperanza Berensztein, Carolina Pepe, Michele Bianchini, Estrella Levy, Javier Goñi, Marco A. Rivarola, and Alicia Belgorosky*

Molecular Biology Laboratory, Endocrinology Department, Garrahan Pediatric Hospital, Buenos Aires, Argentina; Centro de Investigaciones Oncológicas, CIO-FUCA, Buenos Aires, Argentina

* To whom correspondence should be addressed. 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 ER{alpha}, ER{beta}, GPR30 and cP450arom in human adrenal tissue (HAT).

Design: HAT was collected from 3 postnatal age groups: Gr1: < 3 months, n = 12, fetal zone (FeZ) involution; Gr2: 3 months to 6 yr, n = 17, pre-adrenarche; and Gr3: > 6 to 20 yr, n = 12, post-adrenarche period.

Results: ER{beta} mRNA in Gr1 and Gr3 was higher than in Gr2, P < 0.05. By Immunohistochemistry and LCM followed by RT-PCR, ER{beta} was expressed in ZR and FeZ, GPR30 in ZG and adrenal medulla (AM) while ER{alpha} mRNA and protein was undetectable.

cP450arom mRNA in Gr3 was higher than in Gr1 and Gr2 (P < 0.05) and localized to ZG and AM by LCM. cP450arom immunoreactivity was observed in AM in the three Grs and in subcapsular ZG of Gr3. Double immunofluorescence studies revealed that cP450arom and chromogranin A only colocalize in AM 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 than in subjects older than 6 yr.

Conclusions: Our results suggest that estrogens, produced locally in AM, would play a role in ZR functional differentiation through ER{beta}.

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.


Key words: aromatase • estrogen receptors • adrenarche • adrenal medulla




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