Retinoic Acid Receptor Beta (RARβ) Expression Is Not Associated with Postnatal Human Adrenal Cortex Zonation and with the Steroidogenic Pattern of Childhood Virilizing Adrenocortical Tumors

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SUN 203-235-Steroid Hormone Actions, Biosynthesis and Metabolism (posters)
Bench to Bedside
Sunday, April 3, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SUN 211
Cecilia Alonso Burgos*1, Javier Goñi2, Nora Isabel Saraco1, Marco A. Rivarola3, Alicia Belgorosky4 and Maria Sonia Baquedano1
1Endocrine Service, Hospital de Pediatria Garrahan, Buenos Aires, Argentina, 2Hospital de Pediatria Garrahan,Surgery Service, Buenos Aires, Argentina, 3Endocrine Service, Garrahan Pediatric Hospital, Buenos Aires, Argentina, 4Hospital de Pediatria Garrahan, Buenos Aires, Argentina
At adrenarche, the increased androgen production in the zona reticularis (ZR) is characterized by a decrease in HSD3B2. Retinoic acid receptor beta (RARβ) was recently shown to be down-regulated in starved, hyperandrogenic H295R cells model and the study showed evidence that RARβ may regulate HSD3B2 transcription in cooperation with the nuclear hormone receptor, Nur77 (1). Nur77 is critical for HSD3B2 transcription regulation, playing an important role in adult adrenal cortex zonation. Nurr77 expression parallels the minimal expression of HSD3B2 in androgen-producing adrenal cortex tissue such as childhood virilizing adrenocortical tumors (VAT), fetal zone (FeZ) and ZR cells. However, the relevance of RARβ to human adrenal physiology is unknown. The human RARβ gene generates multiple isoforms by use of promoters P1 and P2 and alternative splicing. Reduced expression of RARβ has been reported in human solid tumors often caused by epigenetic silencing of RARβ isoform 2 (RARβ2). Adrenal expression of total RARβ (RARβT) and RARβ2 were studied using quantitative real-time RT-PCR. VAT tissues (n=8, age range 1.3-4.5 yr) and normal human adrenal tissues (HAT) collected from 3 postnatal age groups (2): Gr1: <3 months, n=9, FeZ involution; Gr2: 3 months to 6 yr, n=9, pre-adrenarche; and Gr3: >6 to 20 yr, n=8, post-adrenarche period, were evaluated. Both RARβT and RARβ2 mRNA levels (mean±SD, arbitrary units) were similar among HAT from the 3 age groups (Gr1, 1.44±0.39 and 0.92±0.36; Gr2, 1.32±0.54 and 0.87±0.49; and Gr3, 1.14±0.58 and 0.73±0.53, respectively) and in VAT (RARβT, 0.79±0.55 and RARβ2, 0.51±0.45) without significant differences among them (p>0.05). Laser capture microdissection of ZR and zona fasciculata (ZF) from Gr3 HAT showed no significant differences in RARβT and RARβ2 mRNA expression between micro-dissected ZR (RARβT, 2.42±0.39 and RARβ2, 2.45±0.74) and ZF (RARβT, 2.17±0.31 and RARβ2, 2.14±0.48). Taken together our results suggested that RARβ is not associated with the ZR-specific down-regulation of adrenal HSD3B2 expression of postnatal human adrenal cortex zonation. Furthermore, our study revealed no evidence for RARβ involvement in the regulatory mechanisms underlying hyperandrogenic steroid profile in childhood VAT model.

1) Udhane SS, Pandey AV, Hofer G, Mullis P, Flück C. Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis. Sci Rep 2015 5:10132. 2) Baquedano MS, Saraco N, Berensztein E, Pepe C, Bianchini M, Levy E, Goñi J, Rivarola MA, Belgorosky A Identification and developmental changes of aromatase and estrogen receptor expression in prepubertal and pubertal human adrenal tissues. J Clin Endocrinol Metab 2007 92:2215-2222.

Nothing to Disclose: CA, JG, NIS, MAR, AB, MSB

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Sources of Research Support: CONICET(PIP2014), FONCYT(PICT2013)