Identification and developmental changes of aromatase and estrogen receptor expression in prepubertal and pubertal human adrenal tissues

J Clin Endocrinol Metab. 2007 Jun;92(6):2215-22. doi: 10.1210/jc.2006-2329. Epub 2007 Apr 3.


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)alpha, ERbeta, 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: ERbeta 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, ERbeta was expressed in zona reticularis and fetal zone, GPR30 in zona glomerulosa (ZG) and adrenal medulla, while ERalpha 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 ERbeta. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex / cytology
  • Adrenal Cortex / enzymology
  • Adrenal Cortex / growth & development*
  • Adrenal Medulla / cytology
  • Adrenal Medulla / enzymology
  • Adrenal Medulla / growth & development*
  • Adrenarche / physiology*
  • Adult
  • Aromatase / genetics
  • Aromatase / metabolism*
  • Child
  • Child, Preschool
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism*
  • Exons
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Infant
  • Puberty / physiology
  • RNA, Messenger / metabolism


  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • RNA, Messenger
  • Aromatase