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


METHODS
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.
Baquedano
María Sonia
MS
Endocrinology Service, Hospital de Pediatria Garrahan, C de los Pozos 1881, Buenos Aires, Argentina.
Saraco
Nora
N
Berensztein
Esperanza
E
Pepe
Carolina
C
Bianchini
Michele
M
Levy
Estrella
E
Goñi
Javier
J
Rivarola
Marco A
MA
Belgorosky
Alicia
A
D000293:Adolescent; D000302:Adrenal Cortex / Q000166:cytology / Q000201:enzymology / Q000254:growth & development*; D000313:Adrenal Medulla / Q000166:cytology / Q000201:enzymology / Q000254:growth & development*; D050499:Adrenarche / Q000502:physiology*; D000328:Adult; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007223:Infant; D011627:Puberty / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D001141:Aromatase