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. 1982 Mar;106(3):332–341.

Multiple cellular forms of corticotrophs in surgically removed pituitary adenomas and periadenomatous tissue in Cushing's disease.

R Martin, Y Cetin, H L Fehm, R Fahlbusch, K H Voigt
PMCID: PMC1916215  PMID: 6278938

Abstract

Transsphenoidally removed samples of pituitary adenomas from 14 patients with Cushing's disease and 5 patients with Nelson's syndrome always contained groups of uniform small ACTH-cells. Antibodies against the pro-opiocortin precursor fragments beta-endorphin, ACTH, and 16k-peptide recognized material in typical adenoma cells. A subpopulation of these cells, varying in number from sample to sample, specifically exhibited alpha-melanotropin immunoreactivity. Most periadenomatous samples showed signs of severe degeneration. Typical Crooke cells only occurred in samples from patients with Cushing's syndrome, but, with this exception, no clear differences between pituitaries of patients with Cushing's and Nelson's syndromes could be discerned. Two other forms of ACTH-immunoreactive cells were observed: rare, single, highly immunoreactive cells, with characteristics of both normal and Crooke cells, and numerous syncytial groups of cells in an advanced state of disintegration, presumably the remnants of hyperplastic follicles. The four different corticotrophs are characterized according to their fine structure and immunoreactivity in this study.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Celio M. R. Distribution of beta-endorphin immunoreactive cells in human fetal and adult pituitaries and in pituitary adenomas. J Histochem Cytochem. 1979 Aug;27(8):1215–1215. doi: 10.1177/27.8.479566. [DOI] [PubMed] [Google Scholar]
  2. Celio M. R., Pasi A., Bürgisser E., Buetti G., Höllt V., Gramsch C. 'Proopiocortin fragments' in normal human adult pituitary. Distribution and ultrastructural characterization of immunoreactive cells. Acta Endocrinol (Copenh) 1980 Sep;95(1):27–40. doi: 10.1530/acta.0.0950027. [DOI] [PubMed] [Google Scholar]
  3. Fehm H. L., Voigt K. H. Pathophysiology of Cushing's disease. Pathobiol Annu. 1979;9:225–255. [PubMed] [Google Scholar]
  4. GARMENDIA F., VAUBEL W. E., PFEIFFER E. F. [On the behavior of endogenous ACTH activity in human plasma after enzymatic block of cortisol synthesis with metopirone (SU 4885). I. Studies on persons with normal metabolism]. Klin Wochenschr. 1963 Apr 1;41:317–321. doi: 10.1007/BF01484327. [DOI] [PubMed] [Google Scholar]
  5. Gillies G., Ratter S., Grossman A., Gaillard R., Lowry P. J., Besser G. M., Rees L. H. Secretion of ACTH, LPH and beta-endophin from human pituitary tumours in vitro. Clin Endocrinol (Oxf) 1980 Aug;13(2):197–205. doi: 10.1111/j.1365-2265.1980.tb01042.x. [DOI] [PubMed] [Google Scholar]
  6. Guy J., Leclerc R., Vaudry H., Pelletier G. Localisation immunocytochimique de l'ACTH, de la gamma-endorphine et du précurseur commun de ces peptides dans l'hypophyse humaine. Union Med Can. 1980 Apr;109(4):483–488. [PubMed] [Google Scholar]
  7. Horvath E., Kovacs K., Killinger D. W., Smyth H. S., Platts M. E., Singer W. Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study. Am J Pathol. 1980 Mar;98(3):617–638. [PMC free article] [PubMed] [Google Scholar]
  8. Höllt V., Müller O. A., Fahlbusch R. beta-Endorphin in human plasma: basal and pathologically elevated levels. Life Sci. 1979 Jul 2;25(1):37–44. doi: 10.1016/0024-3205(79)90487-9. [DOI] [PubMed] [Google Scholar]
  9. Krieger D. T., Glick S. M. Growth hormone and cortisol responsiveness in Cushing's syndrome. Relation to a possible central nervous system etiology. Am J Med. 1972 Jan;52(1):25–40. doi: 10.1016/0002-9343(72)90005-8. [DOI] [PubMed] [Google Scholar]
  10. Krieger D. T., Liotta A., Li C. H. Human plasma immunoreactive beta-lipotropin: correlation with basal and stimulated plasma ACTH concentrations. Life Sci. 1977 Dec 15;21(12):1771–1777. doi: 10.1016/0024-3205(77)90157-6. [DOI] [PubMed] [Google Scholar]
  11. LAQUEUR G. L. Cytological changes in human hypophyses after cortisone and ACTH treatment. Science. 1950 Oct 13;112(2911):429–430. doi: 10.1126/science.112.2911.429-a. [DOI] [PubMed] [Google Scholar]
  12. LIDDLE G. W. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 1960 Dec;20:1539–1560. doi: 10.1210/jcem-20-12-1539. [DOI] [PubMed] [Google Scholar]
  13. Lamberts S. W., Stefanko S. Z., de Lange S. A., Fermin H., van der Vijver J. C., Weber R. F., de Jong F. H. Failure of clinical remission after transsphenoidal removal of a microadenoma in a patient with Cushing's disease: multiple hyperplastic and adenomatous cell nets in surrounding pituitary tissue. J Clin Endocrinol Metab. 1980 Apr;50(4):793–795. doi: 10.1210/jcem-50-4-793. [DOI] [PubMed] [Google Scholar]
  14. MAYOR H. D., HAMPTON J. C., ROSARIO B. A simple method for removing the resin from epoxy-embedded tissue. J Biophys Biochem Cytol. 1961 Apr;9:909–910. doi: 10.1083/jcb.9.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mains R. E., Eipper B. A., Ling N. Common precursor to corticotropins and endorphins. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3014–3018. doi: 10.1073/pnas.74.7.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Martin R., Weber E., Voigt K. H. Localization of corticotropin- and endorphin-related peptides in the intermediate lobe of the rat pituitary. Cell Tissue Res. 1979 Feb 15;196(2):307–319. doi: 10.1007/BF00240104. [DOI] [PubMed] [Google Scholar]
  17. Miller W. L., Johnson L. K., Baxter J. D., Roberts J. L. Processing of the precursor to corticotropin and beta-lipotropin in humans. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5211–5215. doi: 10.1073/pnas.77.9.5211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moriarty G. C. Adenohypophysis: ultrastructural cytochemistry. A review. J Histochem Cytochem. 1973 Oct;21(10):855–894. doi: 10.1177/21.10.855. [DOI] [PubMed] [Google Scholar]
  19. Nakai Y., Nakao K., Oki S., Imura H., Li C. H. Presence of immunoreactive beta-endorphin in plasma of patients with Nelson's syndrome and Addison's disease. Life Sci. 1978 Dec 4;23(23):2293–2298. doi: 10.1016/0024-3205(78)90194-7. [DOI] [PubMed] [Google Scholar]
  20. Nakanishi S., Inoue A., Kita T., Nakamura M., Chang A. C., Cohen S. N., Numa S. Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor. Nature. 1979 Mar 29;278(5703):423–427. doi: 10.1038/278423a0. [DOI] [PubMed] [Google Scholar]
  21. Nelson D. H., Sprunt J. G., Mims R. B. Plasma ACTH determinations in 58 patients before or after adrenalectomy for Cushing's syndrome. J Clin Endocrinol Metab. 1966 Jul;26(7):722–728. doi: 10.1210/jcem-26-7-722. [DOI] [PubMed] [Google Scholar]
  22. Oki S., Nakai Y., Nakao K., Imura H. Plasma beta-endorphin responses to somatostatin, thyrotropin-releasing hormone, or vasopressin in Nelson's syndrome. J Clin Endocrinol Metab. 1980 Jan;50(1):194–197. doi: 10.1210/jcem-50-1-194. [DOI] [PubMed] [Google Scholar]
  23. Oki S., Nakao K., Tanaka I., Horii K., Nakai Y., Shimbo S., Watanabe M., Nakane T., Kuwayama A., Kageyama N. Concomitant secretion of adrenocorticotropin, beta-endorphin, and gamma-melanotropin from perfused pituitary tumor cells of Cushing's disease: effects of lysine vasopressin, rat median eminence extracts, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone. J Clin Endocrinol Metab. 1981 Jan;52(1):42–49. doi: 10.1210/jcem-52-1-42. [DOI] [PubMed] [Google Scholar]
  24. Osamura R. Y., Watanabe K., Nakai Y., Imura H. Adrenocorticotropic hormone cells and immunoreactive beta-endorphin cells in the human pituitary gland: normal and pathologic conditions studied by the peroxidase-labeled antibody method. Am J Pathol. 1980 Apr;99(1):105–124. [PMC free article] [PubMed] [Google Scholar]
  25. Raux M. C., Binoux M., Luton J. P., Gourmelen M., Girard F. Studies of ACTH secretion control in 116 cases of Cushing's syndrome. J Clin Endocrinol Metab. 1975 Feb;40(2):186–197. doi: 10.1210/jcem-40-2-186. [DOI] [PubMed] [Google Scholar]
  26. Roberts J. L., Herbert E. Characterization of a common precursor to corticotropin and beta-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4826–4830. doi: 10.1073/pnas.74.11.4826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saeger W. Die Morphologie der paraadenomatösen Adenohypophyse. Ein Beitrag zur Pathogenese der Hypophysenadenome. Virchows Arch A Pathol Anat Histol. 1977 Jan 20;372(4):299–314. doi: 10.1007/BF00432405. [DOI] [PubMed] [Google Scholar]
  28. Scott A. P., Lowry P. J., Bennett H. P., McMartin C., Ratcliffe J. G. Purification and characterization of porcine corticotrophin-like intermediate lobe peptide. J Endocrinol. 1974 Jun;61(3):369–380. doi: 10.1677/joe.0.0610369. [DOI] [PubMed] [Google Scholar]
  29. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  30. Suda T., Abe Y., Demura H., Demura R., Shizume K., Tamahashi N., Sasano N. ACTH, beta-LPH and beta-endorphin in pituitary adenomas of the patients with Cushing's disease: activation of beta-LPH conversion to beta-endorphin. J Clin Endocrinol Metab. 1979 Sep;49(3):475–477. doi: 10.1210/jcem-49-3-475. [DOI] [PubMed] [Google Scholar]
  31. Tanaka K., Nicholson W. E., Orth D. N. The nature of the immunoreactive lipotropins in human plasma and tissue extracts. J Clin Invest. 1978 Jul;62(1):94–104. doi: 10.1172/JCI109119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ueda M., Takeuchi T., Abe K., Miyakawa S., Ohnami S., Yanaihara N. beta-Melanocyte-stimulating hormone immunoreactivity in human pituitaries and ectopic adrenocorticotropin-producing tumors. J Clin Endocrinol Metab. 1980 Mar;50(3):550–556. doi: 10.1210/jcem-50-3-550. [DOI] [PubMed] [Google Scholar]
  33. Weber E., Voigt K. H., Martin R. Pituitary somatotrophs contain [Met]enkephalin-like immunoreactivity. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6134–6138. doi: 10.1073/pnas.75.12.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yoshimi H., Matsukura S., Sueoka S., Fukase M., Yokota M., Hirata Y., Imura H. Radioimmunoassay for beta-endorphin: presence of immunoreactive "big-big" beta-endorphin ("big" beta-lipotropin) in human and rat pituitaries. Life Sci. 1978 Jun 26;22(24):2189–2195. doi: 10.1016/0024-3205(78)90570-2. [DOI] [PubMed] [Google Scholar]

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