Advertisement

Development of Adrenal Cortex Zonation

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Endocrinology and Metabolism Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gruenwald P.
        Embryonic and postnatal development of the adrenal cortex, particularly the zona glomerulosa and accessory nodules.
        Anat Rec. 1946; 95: 391-421
        • Hatano O.
        • Takakusu A.
        • Nomura M.
        • et al.
        Identical origin of adrenal cortex and gonad revealed by expression profiles of Ad4BP/SF-1.
        Genes Cells. 1996; 1: 663-671
        • Luo X.
        • Ikeda Y.
        • Parker K.L.
        A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.
        Cell. 1994; 77: 481-490
        • Morohashi K.
        The ontogenesis of the steroidogenic tissues.
        Genes Cells. 1997; 2: 95-106
        • Le Douarin N.M.
        • Teillet M.A.
        Experimental analysis of the migration and differentiation of neuroblasts of the autonomic nervous system and of neurectodermal mesenchymal derivatives, using a biological cell marking technique.
        Dev Biol. 1974; 41: 162-184
        • Doupe A.J.
        • Landis S.C.
        • Patterson P.H.
        Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity.
        J Neurosci. 1985; 5: 2119-2142
        • Hillarp N.A.
        • Hokfelt B.
        Evidence of adrenaline and noradrenaline in separate adrenal medullary cells.
        Acta Physiol Scand. 1953; 30: 55-68
        • Ce K.
        • Hammer G.D.
        Recent insights into organogenesis of the adrenal cortex.
        Trends Endocrinol Metab. 2002; 13: 200-208
        • Ehrhart-Bornstein M.
        • Hinson J.P.
        • Bornstein S.R.
        • et al.
        Intraadrenal interactions in the regulation of adrenocortical steroidogenesis.
        Endocr Rev. 1998; 19: 101-143
        • Seidl K.
        • Unsicker K.
        The determination of the adrenal medullary cell fate during embryogenesis.
        Dev Biol. 1989; 136: 481-490
        • Finotto S.
        • Krieglstein K.
        • Schober A.
        • et al.
        Analysis of mice carrying targeted mutations of the glucocorticoid receptor gene argues against an essential role of glucocorticoid signalling for generating adrenal chromaffin cells.
        Development. 1999; 126: 2935-2944
        • Gut P.
        • Huber K.
        • Lohr J.
        • et al.
        Lack of an adrenal cortex in Sf1 mutant mice is compatible with the generation and differentiation of chromaffin cells.
        Development. 2005; 132: 4611-4619
        • Bland M.
        • Fowkes R.C.
        • Ingraham H.A.
        Differential requirement for steroidogenic factor-1 gene dosage in adrenal development versus endocrine function.
        Mol Endocrinol. 2004; 18: 941-952
        • Huber K.
        • Combs S.
        • Ernsberger U.
        • et al.
        Generation of neuroendocrine chromaffin cells from sympathoadrenal progenitors: beyond the glucocorticoid hypothesis.
        Ann N Y Acad Sci. 2002; 971: 554-559
        • Unsicker K.
        • Huber K.
        • Schutz G.
        • et al.
        The chromaffin cell and its development.
        Neurochem Res. 2005; 30: 921-925
        • Johannisson E.
        The foetal adrenal cortex in the human. Its ultrastructure at different stages of development and in different functional states.
        Acta Endocrinol (Copenh). 1968; 58: 7
        • Goto M.
        • Piper Hanley K.
        • Marcos J.
        • et al.
        In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development.
        J Clin Invest. 2006; 116: 953-960
        • Hanley N.A.
        • Rainey W.E.
        • Wilson D.I.
        • et al.
        Expression profiles of SF-1, DAX1, and CYP17 in the human fetal adrenal gland: potential interactions in gene regulation.
        Mol Endocrinol. 2001; 15: 57-68
        • Achermann J.C.
        • Meeks J.J.
        • Jameson J.L.
        Phenotypic spectrum of mutations in DAX-1 and SF-1.
        Mol Cell Endocrinol. 2001; 185: 17-25
        • El-Khairi R.
        • Martinez-Aguayo A.
        • Ferraz-de-Souza B.
        • et al.
        Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function.
        Endocr Dev. 2011; 20: 38-46
        • Wong M.
        • Ikeda Y.
        • Luo X.
        • et al.
        Steroidogenic factor 1 plays multiple roles in endocrine development and function.
        Recent Prog Horm Res. 1997; 52: 167-182
        • Doghman M.
        • Karpova T.
        • Rodrigues G.A.
        • et al.
        Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer.
        Mol Endocrinol. 2007; 21: 2968-2987
        • Val P.
        • Martinez-Barbera J.P.
        • Swain A.
        Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage.
        Development. 2007; 134: 2349-2358
        • Bandiera R.
        • Vidal V.P.
        • Motamedi F.J.
        • et al.
        WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP-like progenitors within the adrenal gland.
        Dev Cell. 2013; 27: 5-18
        • Zubair M.
        • Ishihara S.
        • Oka S.
        • et al.
        Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox-Pbx1-Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1.
        Mol Cell Biol. 2006; 26: 4111-4121
        • Zubair M.
        • Parker K.L.
        • Morohashi K.I.
        Developmental links between the fetal and adult zones of the adrenal cortex revealed by lineage tracing.
        Mol Cell Biol. 2008; 28: 7030-7040
        • Ahmad I.
        • Paterson W.F.
        • Lin L.
        • et al.
        A novel missense mutation in DAX-1 with an unusual presentation of X-linked adrenal hypoplasia congenita.
        Horm Res. 2007; 68: 32-37
        • Mantovani G.
        • De Menis E.
        • Borretta G.
        • et al.
        DAX1 and X-linked adrenal hypoplasia congenita: clinical and molecular analysis in five patients.
        Eur J Endocrinol. 2006; 154: 685-689
        • Wood M.
        • Hammer G.D.
        Adrenocortical stem and progenitor cells: unifying model of two proposed origins.
        Mol Cell Endocrinol. 2011; 336: 206-212
        • Scheys J.O.
        • Heaton J.H.
        • Hammer G.D.
        Evidence of adrenal failure in aging Dax1-deficient mice.
        Endocrinology. 2011; 152: 3430-3439
        • Gummow B.M.
        • Scheys J.O.
        • Cancelli V.R.
        • et al.
        Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex.
        Mol Endocrinol. 2006; 20: 2711-2723
        • Kelly V.R.
        • Hammer G.D.
        LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells.
        Mol Cell Endocrinol. 2011; 332: 116-124
        • Khalfallah O.
        • Rouleau M.
        • Barbry P.
        • et al.
        Dax-1 knockdown in mouse embryonic stem cells induces loss of pluripotency and multilineage differentiation.
        Stem Cells. 2009; 27: 1529-1537
        • Feek C.M.
        • Marante D.J.
        • Edwards C.R.
        The hypothalamic-pituitary-adrenal axis.
        Clin Endocrinol Metab. 1983; 12: 597-618
        • Janes M.
        • Chu K.M.
        • Clark A.J.
        • et al.
        Mechanisms of adrenocorticotropin-induced activation of extracellularly regulated kinase 1/2 mitogen-activated protein kinase in the human H295R adrenal cell line.
        Endocrinology. 2008; 149: 1898-1905
        • Pepe G.J.
        • Albrecht E.D.
        Regulation of the primate fetal adrenal cortex.
        Endocr Rev. 1990; 11: 151-176
        • Rainey W.
        • Rehman K.S.
        • Carr B.R.
        Fetal and maternal adrenals in human pregnancy.
        Obstet Gynecol Clin North Am. 2004; 31: 817-835
        • Beshay V.
        • Carr B.R.
        • Rainey W.E.
        The human fetal adrenal gland, corticotropin-releasing hormone, and parturition.
        Semin Reprod Med. 2007; 25: 14-20
        • Hornsby P.J.
        Regulation of adrenocortical cell proliferation in culture.
        Endocr Res. 1984; 10: 259-281
        • Simpson E.R.
        • Waterman M.R.
        Regulation by ACTH of steroid hormone biosynthesis in the adrenal cortex.
        Can J Biochem Cell Biol. 1983; 61: 692-707
        • LeRoith D.
        • Roberts Jr., C.T.
        The insulin-like growth factor system and cancer.
        Cancer Lett. 2003; 195: 127-137
        • Vale W.
        • Spiess J.
        • Rivier C.
        • et al.
        Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin.
        Science. 1981; 213: 1394-1397
        • Spiess J.
        • Rivier J.
        • Rivier C.
        • et al.
        Primary structure of corticotropin-releasing factor from ovine hypothalamus.
        Proc Natl Acad Sci U S A. 1981; 78: 6517-6521
        • Takahashi K.
        • Totsune K.
        • Saruta M.
        • et al.
        Expression of urocortin 3/stresscopin in human adrenal glands and adrenal tumors.
        Peptides. 2006; 27: 178-182
        • Karteris E.
        • Randeva H.S.
        • Grammatopoulos D.K.
        • et al.
        Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals.
        J Clin Endocrinol Metab. 2001; 86: 4512-4519
        • Fukuda T.
        • Takahashi K.
        • Suzuki T.
        • et al.
        Urocortin 1, urocortin 3/stresscopin, and corticotropin-releasing factor receptors in human adrenal and its disorders.
        J Clin Endocrinol Metab. 2005; 90: 4671-4678
        • Dermitzaki E.
        • Tsatsanis C.
        • Minas V.
        • et al.
        Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner.
        Endocrinology. 2007; 148: 1524-1538
        • Sirinanni R.
        • Rehman K.S.
        • Carr B.R.
        • et al.
        Corticotropin-releasing hormone directly stimulates cortisol and the cortisol biosynthetic pathway in human fetal adrenal cells.
        J Clin Endocrinol Metab. 2005; 90: 279-285
        • Andreis P.G.
        • Neri G.
        • Nussdorfer G.G.
        Corticotropin-releasing hormone (CRH) directly stimulates corticosterone secretion by the rat adrenal gland.
        Endocrinology. 1991; 128: 1198-1200
        • Willenberg H.S.
        • Bornstein S.R.
        • Hiroi N.
        • et al.
        Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function.
        Mol Psychiatry. 2000; 5: 137-141
        • Schwartz J.
        • Huo J.S.
        • Piwien-Pilipuk G.
        Growth hormone regulated gene expression.
        Minerva Endocrinol. 2002; 27: 231-241
        • Backlin C.
        • Rastad J.
        • Skogseid B.
        • et al.
        Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex.
        Anticancer Res. 1995; 15: 2453-2459
        • Brice A.L.
        • Cheetham J.E.
        • Bolton V.N.
        • et al.
        Temporal changes in the expression of the insulin-like growth factor II gene associated with tissue maturation in the human fetus.
        Development. 1989; 106: 543-554
        • Coulter C.L.
        • Goldsmith P.C.
        • Mesiano S.
        • et al.
        Functional maturation of the primate fetal adrenal in vivo: I. Role of insulin-like growth factors (IGFs), IGF-I receptor, and IGF binding proteins in growth regulation.
        Endocrinology. 1996; 137: 4487-4498
        • Bendall S.C.
        • Stewart M.H.
        • Menendez P.
        • et al.
        IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro.
        Nature. 2007; 448: 1015-1021
        • Jiang F.
        • Frederick T.J.
        • Wood T.L.
        IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle.
        Dev Biol. 2001; 232: 414-423
        • Pitetti J.L.
        • Calvel P.
        • Romero Y.
        • et al.
        Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice.
        PLoS Genet. 2013; 9: e1003160
        • Morohashi K.
        • Zubair M.
        The fetal and adult adrenal cortex.
        Mol Cell Endocrinol. 2011; 336: 193-197
        • Zubair M.
        • Oka S.
        • Parker K.L.
        • et al.
        Transgenic expression of Ad4BP/SF-1 in fetal adrenal progenitor cells leads to ectopic adrenal formation.
        Mol Endocrinol. 2009; 23: 1657-1667
        • Schulte D.
        • Shapiro I.
        • Reincke M.
        • et al.
        Expression and spatio-temporal distribution of differentiation and proliferation markers during mouse adrenal development.
        Gene Expr Patterns. 2007; 7: 72-81
        • Guasti L.
        • Paul A.
        • Laufer E.
        • et al.
        Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.
        Mol Cell Endocrinol. 2011; 336: 117-122
        • King P.
        • Paul A.
        • Laufer E.
        Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages.
        Proc Natl Acad Sci U S A. 2009; 106: 21185-21190
        • Wood M.A.
        • Acharya A.
        • Finco I.
        • et al.
        Fetal adrenal capsular cells serve as progenitor cells for steroidogenic and stromal adrenocortical cell lineages in M. musculus.
        Development. 2013; 140: 4522-4532
        • Ishimoto H.
        • Jaffe R.B.
        Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit.
        Endocr Rev. 2011; 32: 317-355
        • Havelock J.
        • Auchus R.J.
        • Rainey W.E.
        The rise in adrenal androgen biosynthesis: adrenarche.
        Semin Reprod Med. 2004; 22: 337-347
        • Rosenfield R.L.
        • Lucky A.W.
        Acne, hirsutism, and alopecia in adolescent girls. Clinical expressions of androgen excess.
        Endocrinol Metab Clin North Am. 1993; 22: 507-532
        • Corvalan C.
        • Uauy R.
        • Mericq V.
        Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight.
        Am J Clin Nutr. 2013; 97: 318-325
        • l'Allemand D.
        • Schmidt S.
        • Rousson V.
        • et al.
        Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche.
        Eur J Endocrinol. 2002; 146: 537-543
        • Saenger P.
        • Dimartino-Nardi J.
        Premature adrenarche.
        J Endocrinol Invest. 2001; 24: 724-733
        • Pintor C.
        • Loche S.
        • Faedda A.
        • et al.
        Adrenal androgens in obese boys before and after weight loss.
        Horm Metab Res. 1984; 16: 544-548
        • Howard E.
        The effect of dietary factors on the adrenal X zone.
        Fed Proc. 1947; 6: 133
        • Tanaka S.
        • Matsuzawa A.
        What mouse contributed the first representation of the adrenal cortex X zone?.
        Jikken Dobutsu. 1993; 42 ([in Japanese]): 305-316
        • Nishimoto K.
        • Nakagawa K.
        • Li D.
        • et al.
        Adrenocortical zonation in humans under normal and pathological conditions.
        J Clin Endocrinol Metab. 2010; 95: 2296-2305
        • Nakamura Y.
        • Maekawa T.
        • Felizola S.J.
        • et al.
        Adrenal CYP11B1/2 expression in primary aldosteronism: immunohistochemical analysis using novel monoclonal antibodies.
        Mol Cell Endocrinol. 2014; 392: 73-79
        • Gomez-Sanchez C.E.
        • Qi X.
        • Velarde-Miranda C.
        • et al.
        Development of monoclonal antibodies against human CYP11B1 and CYP11B2.
        Mol Cell Endocrinol. 2014; 383: 111-117
        • Chamoux E.
        • Otis M.
        • Gallo-Payet N.
        A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland.
        Braz J Med Biol Res. 2005; 38: 1495-1503
        • Chamoux E.
        • Narcy A.
        • Lehoux J.G.
        • et al.
        Fibronectin, laminin, and collagen IV as modulators of cell behavior during adrenal gland development in the human fetus.
        J Clin Endocrinol Metab. 2002; 87: 1819-1828
        • Chamoux E.
        • Bolduc L.
        • Lehoux J.G.
        • et al.
        Identification of extracellular matrix components and their integrin receptors in the human fetal adrenal gland.
        J Clin Endocrinol Metab. 2001; 86: 2090-2098
        • Otis M.
        • Campbell S.
        • Payet M.D.
        • et al.
        Expression of extracellular matrix proteins and integrins in rat adrenal gland: importance for ACTH-associated functions.
        J Endocrinol. 2007; 193: 331-347
        • Cheng C.Y.
        • Hornsby P.J.
        Expression of 11 beta-hydroxylase and 21-hydroxylase in long-term cultures of bovine adrenocortical cells requires extracellular matrix factors.
        Endocrinology. 1992; 130: 2883-2889
        • Filippi L.
        • Sardella B.
        • Ciorra A.
        • et al.
        Tumor thrombus in the renal vein from an adrenal metastasis of lung cancer: 18FDG PET/CT findings.
        Cancer Biother Radiopharm. 2014; 29: 189-192
        • Puech A.
        • Pages A.
        • Comelade P.
        Cutaneous metastases as the first manifestation of a cancer of the lungs; adrenal metastasis; terminal acute adrenal insufficiency.
        Montp Med. 1955; 47 ([in French]): 565-566
        • Onuigbo W.I.
        Lung cancer metastasis to adrenal cortical adenomas.
        J Pathol Bacteriol. 1963; 86: 541-543
        • Lever J.D.
        Observations on the adrenal blood vessels in the rat.
        J Anat. 1952; 86: 459-467
        • Anson B.J.
        • Cauldwell E.W.
        • Beaton L.E.
        • et al.
        The blood supply of the kidney, suprarenal gland, and associated structures.
        Surg Gynecol Obstet. 1947; 84: 313-320
        • Johnstone F.R.
        The suprarenal veins.
        Am J Surg. 1957; 94: 615-620
        • Monkhouse W.S.
        • Khalique A.
        The adrenal and renal veins of man and their connections with azygos and lumbar veins.
        J Anat. 1986; 146: 105-115
        • Gagnon R.
        The venous drainage of the human adrenal gland.
        Rev Can Biol. 1956; 14: 350-359
        • Engeland W.C.
        Functional innervation of the adrenal cortex by the splanchnic nerve.
        Horm Metab Res. 1998; 30: 311-314
        • Hinson J.P.
        • Cameron L.A.
        • Purbrick A.
        • et al.
        The role of neuropeptides in the regulation of adrenal vascular tone: effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, neurotensin, Met-enkephalin, and Leu-enkephalin on perfusion medium flow rate in the intact perfused rat adrenal.
        Regul Pept. 1994; 51: 55-61
        • Li Q.
        • Johansson H.
        • Kjellman M.
        • et al.
        Neuroendocrine differentiation and nerves in human adrenal cortex and cortical lesions.
        APMIS. 1998; 106: 807-817
        • Burnay M.M.
        • Python C.P.
        • Vallotton M.B.
        • et al.
        Role of the capacitative calcium influx in the activation of steroidogenesis by angiotensin-II in adrenal glomerulosa cells.
        Endocrinology. 1994; 135: 751-758
        • Johnson B.B.
        • Lieberman A.H.
        • Mulrow P.J.
        Aldosterone excretion in normal subjects depleted of sodium and potassium.
        J Clin Invest. 1957; 36: 757-766
        • Laragh J.H.
        • Stoerk H.C.
        A study of the mechanism of secretion of the sodium-retaining hormone (aldosterone).
        J Clin Invest. 1957; 36: 383-392
        • McCaa R.E.
        • Gillespie J.B.
        Effects of captopril and enalapril on sodium excretion and blood pressure in sodium-deficient dogs.
        Fed Proc. 1984; 43: 1336-1341
        • Deane H.W.
        • Bergner G.E.
        Chemical and cytochemical studies of the rat's adrenal cortex following the administration of pituitary adrenocorticotropic hormone (ACTH).
        J Clin Endocrinol Metab. 1947; 7: 457
        • Hills A.G.
        • Thorn G.W.
        An estimation of the quantity of 11–17-oxysteroid excretion by the human adrenal stimulated by ACTH.
        J Clin Endocrinol Metab. 1948; 8: 606
        • Mason H.L.
        • Power M.H.
        • Rynearson E.H.
        • et al.
        Results of administration of anterior pituitary adrenocorticotropic hormone to a normal human being.
        J Biol Chem. 1947; 169: 223
        • Ingle D.J.
        • Prestrud M.C.
        • Li C.H.
        A further study of the essentiality of the adrenal cortex in mediating the metabolic effects of adrenocorticotrophic hormone.
        Endocrinology. 1948; 43: 202-207
        • Bellamy D.
        • Leonard R.A.
        The effect of cortisol on the activity of glutamate-pyruvate transaminase and the formation of glycogen and urea in starved rats.
        Biochem J. 1964; 93: 331-336
        • Sie H.G.
        • Hablanian A.
        • Fishman W.H.
        Solubilization of mouse liver glycogen synthetase and phosphorylase during starvation glycogenolysis and its reversal by cortisol.
        Nature. 1964; 201: 393-394
        • Bandy H.E.
        • Darrach M.
        • Newsom S.E.
        • et al.
        Metabolism of adrenal steroids in the mouse. I. Observations on 20alpha-dihydrocorticosterone and corticosterone in the plasma of mice treated with corticotropin.
        Can J Biochem Physiol. 1956; 34: 913-918
        • Halberg F.
        • Albrecht P.G.
        • Bittner J.J.
        Corticosterone rhythm of mouse adrenal in relation to serum corticosterone and sampling.
        Am J Physiol. 1959; 197: 1083-1085
        • Halberg F.
        • Haus E.
        Corticosterone in mouse adrenal in relation to sex and heterotopic pituitary isografting.
        Am J Physiol. 1960; 199: 859-862
        • Ortega E.
        • Rodriguez C.
        • Strand L.J.
        • et al.
        Effects of cloprednol and other corticosteroids on hypothalamic-pituitary-adrenal axis function.
        J Int Med Res. 1976; 4: 326-337
        • Storrs F.J.
        Use and abuse of systemic corticosteroid therapy.
        J Am Acad Dermatol. 1979; 1: 95-106
        • Conley A.J.
        • Pattison J.C.
        • Bird I.M.
        Variations in adrenal androgen production among (nonhuman) primates.
        Semin Reprod Med. 2004; 22: 311-326
        • Davison B.
        • Large D.M.
        • Anderson D.C.
        • et al.
        Basal steroid production by the zona reticularis of the guinea-pig adrenal cortex.
        J Steroid Biochem. 1983; 18: 285-290
        • Hyatt P.J.
        • Bhatt K.
        • Tait J.F.
        Steroid biosynthesis by zona fasciculata and zona reticularis cells purified from the mammalian adrenal cortex.
        J Steroid Biochem. 1983; 19: 953-959
        • Kaufman F.R.
        • Stanczyk F.Z.
        • Matteri R.K.
        • et al.
        Dehydroepiandrosterone and dehydroepiandrosterone sulfate metabolism in human genital skin.
        Fertil Steril. 1990; 54: 251-254
        • Rosenfield R.L.
        Hirsutism and the variable response of the pilosebaceous unit to androgen.
        J Investig Dermatol Symp Proc. 2005; 10: 205-208
        • Pelletier G.
        Expression of steroidogenic enzymes and sex-steroid receptors in human prostate.
        Best Pract Res Clin Endocrinol Metab. 2008; 22: 223-228
        • Rege J.
        • Nakamura Y.
        • Satoh F.
        • et al.
        Liquid chromatography-tandem mass spectrometry analysis of human adrenal vein 19-carbon steroids before and after ACTH stimulation.
        J Clin Endocrinol Metab. 2013; 98: 1182-1188
        • Pabon J.E.
        • Li X.
        • Lei Z.M.
        • et al.
        Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands.
        J Clin Endocrinol Metab. 1996; 81: 2397-2400
        • Jaffe R.B.
        • Seron-Ferre M.
        • Crickard K.
        • et al.
        Regulation and function of the primate fetal adrenal gland and gonad.
        Recent Prog Horm Res. 1981; 37: 41-103
        • Vuorenoja S.
        • Rivero-Muller A.
        • Kiiveri S.
        • et al.
        Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6.
        Mol Cell Endocrinol. 2007; 269: 38-45
        • Lacroix A.
        • Hamet P.
        • Boutin J.M.
        Leuprolide acetate therapy in luteinizing hormone–dependent Cushing's syndrome.
        N Engl J Med. 1999; 341: 1577-1581
        • Baker B.L.
        A comparison of the histological changes induced by experimental hyperadrenocorticalism and inanition.
        Recent Prog Horm Res. 1952; 7: 331
        • Zwemer R.L.
        • Wotton R.M.
        • Norkus M.G.
        A study of corticoadrenal cells.
        Anat Rec. 1938; 72: 249-263
        • Salmon T.N.
        • Zwemer R.L.
        A study of the life history of cortico-adrenal gland cells of the rat by means of trypan blue injections.
        Anat Rec. 1941; 80: 421-429
        • Malendowicz L.K.
        • Dembinska M.
        Proliferation and distribution of adrenocortical cells in ACTH treated female hamsters.
        Folia Histochem Cytobiol. 1990; 28: 51-59
        • Stachowiak A.
        • Nussdorfer G.G.
        • Malendowicz L.K.
        Proliferation and distribution of adrenocortical cells in the gland of ACTH- or dexamethasone-treated rats.
        Histol Histopathol. 1990; 5: 25-29
        • Sasano H.
        • Imatani A.
        • Shizawa S.
        • et al.
        Cell proliferation and apoptosis in normal and pathologic human adrenal.
        Mod Pathol. 1995; 8: 11-17
        • Morley S.D.
        • Viard I.
        • Chung B.C.
        • et al.
        Variegated expression of a mouse steroid 21-hydroxylase/beta- galactosidase transgene suggests centripetal migration of adrenocortical cells.
        Mol Endocrinol. 1996; 10: 585-598
        • Ching S.
        • Vilain E.
        Targeted disruption of Sonic Hedgehog in the mouse adrenal leads to adrenocortical hypoplasia.
        Genesis. 2009; 47: 628-637
        • Huang C.
        • Miyagawa S.
        • Matsumaru D.
        • et al.
        Progenitor cell expansion and organ size of mouse adrenal is regulated by sonic hedgehog.
        Endocrinology. 2010; 151: 1119-1128
        • Alex K.
        • Barlaskar F.M.
        • Heaton J.H.
        • et al.
        In search of adrenocortical stem and progenitor cells.
        Endocr Rev. 2009; 30: 241-263
        • Kim A.C.
        • Reuter A.L.
        • Zubair M.
        • et al.
        Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex.
        Development. 2008; 135: 2593-2602
        • Berthon A.
        • Sahut-Barnola I.
        • Lambert-Langlais S.
        • et al.
        Constitutive beta-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development.
        Hum Mol Genet. 2010; 19: 1561-1576
        • Assie G.
        • Guillaud-Bataille M.
        • Ragazzon B.
        • et al.
        The pathophysiology, diagnosis and prognosis of adrenocortical tumors revisited by transcriptome analyses.
        Trends Endocrinol Metab. 2010; 21: 325-334
        • Schteingart D.E.
        • Doherty G.M.
        • Gauger P.G.
        • et al.
        Management of patients with adrenal cancer: recommendations of an international consensus conference.
        Endocr Relat Cancer. 2005; 12: 667-680
        • Berthon A.
        • Drelon C.
        • Ragazzon B.
        • et al.
        WNT/beta-catenin signalling is activated in aldosterone-producing adenomas and controls aldosterone production.
        Hum Mol Genet. 2014; 23: 889-905
        • Mizusaki H.
        • Kawabe K.
        • Mukai T.
        • et al.
        Dax-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) gene transcription is regulated by wnt4 in the female developing gonad.
        Mol Endocrinol. 2003; 17: 507-519
        • Walczak E.M.
        • Kuick R.
        • Finco I.
        • et al.
        Wnt signaling inhibits adrenal steroidogenesis by cell-autonomous and non-cell-autonomous mechanisms.
        Mol Endocrinol. 2014; 28: 1471-1486
        • Freedman B.D.
        • Kempna P.B.
        • Carlone D.L.
        • et al.
        Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells.
        Dev Cell. 2013; 26: 666-673
        • Arboleda V.A.
        • Lee H.
        • Parnaik R.
        • et al.
        Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome.
        Nat Genet. 2012; 44: 788-792
        • Achermann J.C.
        • Ito M.
        • Hindmarsh P.C.
        • et al.
        A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans.
        Nat Genet. 1999; 22: 125-126
        • Habiby R.L.
        • Boepple P.
        • Nachtigall L.
        • et al.
        Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalmic and pituitary defects in gonadotropin production.
        J Clin Invest. 1996; 98: 1055-1062
        • Mandel H.
        • Shemer R.
        • Borochowitz Z.U.
        • et al.
        SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4.
        Am J Hum Genet. 2008; 82: 39-47
        • Clark A.J.
        • McLoughlin L.
        • Grossman A.
        Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor.
        Lancet. 1993; 341: 461-462
        • Gineau L.
        • Cognet C.
        • Kara N.
        • et al.
        Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency.
        J Clin Invest. 2012; 122: 821-832
        • Hughes C.R.
        • Guasti L.
        • Meimaridou E.
        • et al.
        MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans.
        J Clin Invest. 2012; 122: 814-820
        • Meimaridou E.
        • Kowalczyk J.
        • Guasti L.
        • et al.
        Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency.
        Nat Genet. 2012; 44: 740-742
        • Jackson R.S.
        • Creemers J.W.
        • Farooqi I.S.
        • et al.
        Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency.
        J Clin Invest. 2003; 112: 1550-1560
        • Krude H.
        • Biebermann H.
        • Luck W.
        • et al.
        Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans.
        Nat Genet. 1998; 19: 155-157
        • Dattani M.T.
        • Martinez-Barbera J.P.
        • Thomas P.Q.
        • et al.
        Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse.
        Nat Genet. 1998; 19: 125-133
        • Wu W.
        • Cogan J.D.
        • Pfäffle R.W.
        • et al.
        Mutations in PROP1 cause familial combined pituitary hormone deficiency.
        Nat Genet. 1998; 18: 147-149
        • Wettstein M.
        • Diez L.F.
        • Twohig M.
        • et al.
        The role of birth injury and the consequences of inadequately treated hypogonadism in longstanding panhypopituitarism.
        Conn Med. 1996; 60: 583-586
        • Cohen L.E.
        Genetic disorders of the pituitary.
        Curr Opin Endocrinol Diabetes Obes. 2012; 19: 33-39
        • Speiser P.W.
        • Azziz R.
        • Baskin L.S.
        • et al.
        Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline.
        J Clin Endocrinol Metab. 2010; 95: 4133-4160
        • Nimkarn S.
        • New M.I.
        Prenatal diagnosis and treatment of congenital adrenal hyperplasia.
        Horm Res. 2007; 67: 53-60
        • Nimkarn S.
        • Lin-Su K.
        • New M.I.
        Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia.
        Pediatr Clin North Am. 2011; 58: 1281-1300
        • Hauffa B.
        • Hiort O.
        P450 side-chain cleavage deficiency–a rare cause of congenital adrenal hyperplasia.
        Endocr Dev. 2011; 20: 54-62
        • Krone N.
        • Arlt W.
        Genetics of congenital adrenal hyperplasia.
        Best Pract Res Clin Endocrinol Metab. 2009; 23: 181-192
        • Lekarev O.
        • Mallet D.
        • Yuen T.
        • et al.
        Congenital lipoid adrenal hyperplasia (a rare form of adrenal insufficiency and ambiguous genitalia) caused by a novel mutation of the steroidogenic acute regulatory protein gene.
        Eur J Pediatr. 2012; 171: 787-793
        • Louiset E.
        • Duparc C.
        • Young J.
        • et al.
        Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.
        N Engl J Med. 2013; 369: 2115-2125
        • Groussin L.
        • Jullian E.
        • Perlemoine K.
        • et al.
        Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease.
        J Clin Endocrinol Metab. 2002; 87: 4324-4329
        • Lacroix A.
        ACTH-independent macronodular adrenal hyperplasia.
        Best Pract Res Clin Endocrinol Metab. 2009; 23: 245-259
        • Ghayee H.K.
        • Rege J.
        • Watumull L.M.
        • et al.
        Clinical, biochemical, and molecular characterization of macronodular adrenocortical hyperplasia of the zona reticularis: a new syndrome.
        J Clin Endocrinol Metab. 2011; 96: E243-E250
        • Hayashi Y.
        • Takeda Y.
        • Kaneko K.
        • et al.
        A case of Cushing's syndrome due to ACTH-independent bilateral macronodular hyperplasia associated with excessive secretion of mineralocorticoids.
        Endocr J. 1998; 45: 485-491
        • Lerario A.M.
        • Moraitis A.
        • Hammer G.D.
        Genetics and epigenetics of adrenocortical tumors.
        Mol Cell Endocrinol. 2014; 386: 67-84
        • Espiard S.
        • Ragazzon B.
        • Bertherat J.
        Protein kinase A alterations in adrenocortical tumors.
        Horm Metab Res. 2014; 8: 8
        • Grumbach M.M.
        • Biller B.M.
        • Braunstein G.D.
        • et al.
        Management of the clinically inapparent adrenal mass (“incidentaloma”).
        Ann Intern Med. 2003; 138: 424-429
        • Arnaldi G.
        • Boscaro M.
        Adrenal incidentaloma.
        Best Pract Res Clin Endocrinol Metab. 2012; 26: 405-419
        • Mulatero P.
        • Stowasser M.
        • Loh K.C.
        • et al.
        Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents.
        J Clin Endocrinol Metab. 2004; 89: 1045-1050
        • Fernandes-Rosa F.L.
        • Williams T.A.
        • Riester A.
        • et al.
        Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma.
        Hypertension. 2014; 64: 354-361
        • Choi M.
        • Scholl U.I.
        • Yue P.
        • et al.
        K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.
        Science. 2011; 331: 768-772
        • Krapivinsky G.
        • Gordon E.A.
        • Wickman K.
        • et al.
        The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
        Nature. 1995; 374: 135-141
        • Monticone S.
        • Hattangady N.G.
        • Nishimoto K.
        • et al.
        Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenocortical cells.
        J Clin Endocrinol Metab. 2012; 97: 2011-3132
        • Monticone S.
        • Else T.
        • Mulatero P.
        • et al.
        Understanding primary aldosteronism: impact of next generation sequencing and expression profiling.
        Mol Cell Endocrinol. 2015; 399: 311-320
        • Cao Y.
        • He M.
        • Gao Z.
        • et al.
        Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome.
        Science. 2014; 344: 913-917
        • Goh G.
        • Scholl U.I.
        • Healy J.M.
        • et al.
        Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors.
        Nat Genet. 2014; 46: 613-617
        • Sato Y.
        • Maekawa S.
        • Ishii R.
        • et al.
        Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.
        Science. 2014; 344: 917-920
        • Kebebew E.
        • Reiff E.
        • Duh Q.Y.
        • et al.
        Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress?.
        World J Surg. 2006; 30: 872-878
        • Kerkhofs T.M.
        • Verhoeven R.H.
        • Van der Zwan J.M.
        • et al.
        Adrenocortical carcinoma: a population-based study on incidence and survival in the Netherlands since 1993.
        Eur J Cancer. 2013; 49: 2579-2586
        • Abiven G.
        • Coste J.
        • Groussin L.
        • et al.
        Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients.
        J Clin Endocrinol Metab. 2006; 91: 2650-2655
        • Wajchenberg B.L.
        • Albergaria Pereira M.A.
        • Medonca B.B.
        • et al.
        Adrenocortical carcinoma: clinical and laboratory observations.
        Cancer. 2000; 88: 711-736
        • Fassnacht M.
        • Allolio B.
        Clinical management of adrenocortical carcinoma.
        Best Pract Res Clin Endocrinol Metab. 2009; 23: 273-289
        • Beuschlein F.
        • Reincke M.
        • Karl M.
        • et al.
        Clonal composition of human adrenocortical neoplasms.
        Cancer Res. 1994; 54: 4927-4932
        • Gicquel C.
        • Leblond-Francillard M.
        • Bertagna X.
        • et al.
        Clonal analysis of human adrenocortical carcinomas and secreting adenomas.
        Clin Endocrinol. 1994; 40: 465-477
        • Kartheuser A.
        • Walon C.
        • West S.
        • et al.
        Familial adenomatous polyposis associated with multiple adrenal adenomas in a patient with a rare 3' APC mutation.
        J Med Genet. 1999; 36: 65-67
        • Marshall W.H.
        • Martin F.I.
        • Mackay I.R.
        Gardner's syndrome with adrenal carcinoma.
        Australas Ann Med. 1967; 16: 242-244
        • Kim W.
        • Kim M.
        • Jho E.H.
        Wnt/β-catenin signalling: from plasma membrane to nucleus.
        Biochem J. 2013; 450: 9-21
        • Tissier F.
        • Cavard C.
        • Groussin L.
        • et al.
        Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors.
        Cancer Res. 2005; 65: 7622-7627
        • Tadjine M.
        • Lampron A.
        • Ouadi L.
        • et al.
        Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas.
        Clin Endocrinol. 2008; 68: 264-270
        • Assié G.
        • Letouzé E.
        • Fassnacht M.
        • et al.
        Integrated genomic characterization of adrenocortical carcinoma.
        Nat Genet. 2014; 46: 607-612
        • Choufani S.
        • Shuman C.
        • Weksberg R.
        Beckwith-Wiedemann syndrome.
        Am J Med Genet C Semin Med Genet. 2010; 154C: 343-354
        • Gicquel C.
        • Bertagna X.
        • Gaston V.
        • et al.
        Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors.
        Cancer Res. 2001; 61: 6762-6767
        • Giordano T.J.
        • Kuick R.
        • Else T.
        • et al.
        Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling.
        Clin Cancer Res. 2009; 15: 668-676
        • Giordano T.J.
        • Thomas D.G.
        • Kuick R.
        • et al.
        Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis.
        Am J Pathol. 2003; 162: 521-531
        • Gicquel C.
        • Raffin-Sanson M.L.
        • Gaston V.
        • et al.
        Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors.
        J Clin Endocrinol Metab. 1997; 82: 2559-2565
        • Weber M.M.
        • Fottner C.
        • Schmidt P.
        • et al.
        Postnatal overexpression of insulin-like growth factor II in transgenic mice is associated with adrenocortical hyperplasia and enhanced steroidogenesis.
        Endocrinology. 1999; 140: 1537-1543
        • Heaton J.H.
        • Wood M.A.
        • Kim A.C.
        • et al.
        Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and beta-catenin.
        Am J Pathol. 2012; 181: 1017-1033
        • Almeida M.Q.
        • Fragoso M.C.
        • Lotfi C.F.
        • et al.
        Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors.
        J Clin Endocrinol Metab. 2008; 93: 3524-3531
        • Barlaskar F.M.
        • Spalding A.C.
        • Heaton J.H.
        • et al.
        Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma.
        J Clin Endocrinol Metab. 2009; 94: 204-212
        • Haluska P.
        • Worden F.
        • Olmos D.
        • et al.
        Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma.
        Cancer Chemother Pharmacol. 2010; 65: 765-773
        • Lerario A.M.
        • Worden F.P.
        • Ramm C.A.
        • et al.
        The combination of insulin-like growth factor receptor 1 (IGF1R) antibody cixutumumab and mitotane as a first-line therapy for patients with recurrent/metastatic adrenocortical carcinoma: a multi-institutional NCI-sponsored trial.
        Horm Cancer. 2014; 5: 232-239
        • Naing A.
        • Lorusso P.
        • Fu S.
        • et al.
        Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma.
        Br J Cancer. 2013; 108: 826-830
        • Li F.P.
        • Fraumeni J.F.
        • Mulvihill J.J.
        • et al.
        A cancer family syndrome in twenty-four kindreds.
        Cancer Res. 1988; 48: 5358-5362
        • Bougeard G.
        • Sesboüé R.
        • Baert-Desurmont S.
        • et al.
        Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families.
        J Med Genet. 2008; 45: 535-538
        • Libè R.
        • Groussin L.
        • Tissier F.
        • et al.
        Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity.
        Clin Cancer Res. 2007; 13: 844-850
        • Waldmann J.
        • Patsalis N.
        • Fendrich V.
        • et al.
        Clinical impact of TP53 alterations in adrenocortical carcinomas.
        Langenbecks Arch Surg. 2012; 397: 209-216
        • Herrmann L.J.
        • Heinze B.
        • Fassnacht M.
        • et al.
        TP53 germline mutations in adult patients with adrenocortical carcinoma.
        J Clin Endocrinol Metab. 2012; 97: E476-E485
        • Raymond V.M.
        • Else T.
        • Everett J.N.
        • et al.
        Prevalence of germline TP53 mutations in a prospective series of unselected patients with adrenocortical carcinoma.
        J Clin Endocrinol Metab. 2013; 98: E119-E125
        • Ribeiro R.C.
        • Sandrini F.
        • Figueiredo B.
        • et al.
        An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.
        Proc Natl Acad Sci U S A. 2001; 98: 9330-9335
        • Varley J.M.
        • McGown G.
        • Thorncroft M.
        • et al.
        Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors.
        Am J Hum Genet. 1999; 65: 995-1006
        • Wagner J.
        • Portwine C.
        • Rabin K.
        • et al.
        High frequency of germline p53 mutations in childhood adrenocortical cancer.
        J Natl Cancer Inst. 1994; 86: 1707-1710
        • Choudhary B.
        • Karande A.A.
        • Raghavan S.C.
        Telomere and telomerase in stem cells: relevance in ageing and disease.
        Front Biosci. 2012; 4: 16-30
        • Ju Z.
        • Rudolph K.L.
        Telomeres and telomerase in stem cells during aging and disease.
        Genome Dyn. 2006; 1: 84-103
        • Kim N.W.
        • Piatyszek M.A.
        • Prowse K.R.
        • et al.
        Specific association of human telomerase activity with immortal cells and cancer.
        Science. 1994; 266: 2011-2015
        • Keegan C.E.
        • Hutz J.E.
        • Else T.
        • et al.
        Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator.
        Hum Mol Genet. 2005; 14: 113-123
        • Else T.
        • Trovato A.
        • Kim A.C.
        • et al.
        Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis.
        Cancer Cell. 2009; 15: 465-476
        • Shackleton M.
        • Quintana E.
        • Fearon E.R.
        • et al.
        Heterogeneity in cancer: cancer stem cells versus clonal evolution.
        Cell. 2009; 138: 822-829
        • Gupta P.B.
        • Fillmore C.M.
        • Jiang G.
        • et al.
        Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells.
        Cell. 2011; 146: 633-644
        • Welte Y.
        • Adjaye J.
        • Lehrach H.R.
        • et al.
        Cancer stem cells in solid tumors: elusive or illusive? Cell communication and signaling.
        Cell Commun Signal. 2010; 8: 6
        • Lichtenauer U.D.
        • Shapiro I.
        • Geiger K.
        • et al.
        Side population does not define stem cell-like cancer cells in the adrenocortical carcinoma cell line NCI h295R.
        Endocrinology. 2008; 149: 1314-1322