Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia

BMC Endocrine Disorders

Tânia ASS Bachega²  Berenice B Mendonca²  Francisco T Denes⁴  Osmar Monte¹  Marta Ribeiro¹  Beatriz M P Mariani²  Antonio M Lerario²  Luciana P Brito²  Laura C Kaupert²  Madson Q Almeida³ 

[1] Unidade de Endocrinologia e Metabologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo, São Paulo, Brasil;Divisão de Endocrinologia e Metabologia, Laboratório de Hormônios e Genética Molecular/LIM42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, 2 andar, Bloco 6, São Paulo, SP 05403-900, Brasil;Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil;Serviço de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil

关键词: Clonality analysis;    Androgen receptor;    MC2R;    ACTH;    Congenital adrenal hyperplasia;    Adrenal myelolipoma;   

Others  :  864922
DOI  :  10.1186/1472-6823-14-42

 received in 2014-01-28, accepted in 2014-05-08,  发布年份 2014

【 摘 要 】

Background

Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far.

Methods

We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases.

Results

The MC2R gene was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors. In addition, X-chromosome inactivation pattern analysis showed a polyclonal origin in all tumors, suggesting a stimulatory effect as the trigger for tumor development.

Conclusion

These findings are the first evidence for MC2R or AR overexpression in giant bilateral myelolipomas from poor-compliance CAH patients.

【 授权许可】

   
2014 Almeida et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Hagiwara H, Usui T, Kimura T, Tagami T, Naruse M, Minamiguchi S, Kato T, Okuno H, Shimatsu A: Lack of ACTH and androgen receptor expression in a giant adrenal myelolipoma associated with 21-hydroxylase deficiency. Endocr Pathol 2008, 19(2):122-127.
• [2]Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR: The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev 2004, 25(2):309-340.
• [3]Hisamatsu H, Sakai H, Tsuda S, Shigematsu K, Kanetake H: Combined adrenal adenoma and myelolipoma in a patient with Cushing's syndrome: case report and review of the literature. Int J Urol 2004, 11(6):416-418.
• [4]Maschler I, Rosenmann E, Ehrenfeld EN: Ectopic functioning adrenocortico-myelolipoma in longstanding Nelson's syndrome. Clin Endocrinol (Oxf) 1979, 10(5):493-497.
• [5]Nermoen I, Rorvik J, Holmedal SH, Hykkerud DL, Fougner KJ, Svartberg J, Husebye ES, Lovas K: High frequency of adrenal myelolipomas and testicular adrenal rest tumours in adult Norwegian patients with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency. Clin Endocrinol (Oxf) 2011, 75(6):753-759.
• [6]German-Mena E, Zibari GB, Levine SN: Adrenal myelolipomas in patients with congenital adrenal hyperplasia: review of the literature and a case report. Endocr Pract 2011, 17(3):441-447.
• [7]Ioannidis O, Papaemmanouil S, Chatzopoulos S, Paraskevas G, Konstantara A, Kotronis A, Kakoutis E, Makrantonakis A: Giant bilateral symptomatic adrenal myelolipomas associated with congenital adrenal hyperplasia. Pathol Oncol Res 2011, 17(3):775-778.
• [8]McGeoch SC, Olson S, Krukowski ZH, Bevan JS: Giant bilateral myelolipomas in a man with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2012, 97(2):343-344.
• [9]Mermejo LM, Elias Junior J, Saggioro FP, Tucci Junior S, Castro M, Moreira AC, Elias PC: Giant adrenal myelolipoma associated with 21-hydroxylase deficiency: unusual association mimicking an androgen-secreting adrenocortical carcinoma. Arq Bras Endocrinol Metabol 2010, 54(4):419-424.
• [10]Plaut A: Myelolipoma in the adrenal cortex; myeloadipose structures. Am J Pathol 1958, 34(3):487-515.
• [11]Dean G: Myelolipoma of the adrenal gland. Scott Med J 1971, 16(12):513-518.
• [12]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25(4):402-408.
• [13]Kaupert LC, Billerbeck AE, Brito VN, Mendonca BB, Bachega TA: Could the leukocyte x chromosome inactivation pattern be extrapolated to hair bulbs? Horm Res Paediatr 2010, 73(4):238-243.
• [14]Rocha RO, Billerbeck AE, Pinto EM, Melo KF, Lin CJ, Longui CA, Mendonca BB, Bachega TA: The degree of external genitalia virilization in girls with 21-hydroxylase deficiency appears to be influenced by the CAG repeats in the androgen receptor gene. Clin Endocrinol (Oxf) 2008, 68(2):226-232.
• [15]Selye H, Stone H: Hormonally induced transformation of adrenal into myeloid tissue. Am J Pathol 1950, 26(2):211-233.
• [16]Kim SC, Ju W, Mahavni V, Geisler JP, Buller RE: CAG repeat length in exon 1 of the androgen receptor gene is related to age of diagnosis but not germ line BRCA1 mutation status in ovarian cancer. Int J Gynecol Cancer 2006, 16(Suppl 1):190-194.
• [17]Gururajan M, Posadas EM, Chung LW: Future perspectives of prostate cancer therapy. Transl Androl Urol 2012, 1(1):19-32.
• [18]Wu MH, Chou YC, Yu CP, Yang T, You SL, Chen CJ, Sun CA: Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility. Eur J Cancer Prev 2008, 17(4):317-322.