Virchows Archiv B

, 49:93 | Cite as

Aminoglutethimide-stimulated corticotrophs

An immunocytologic, ultrastructural and immunoelectron microscopic study of the rat adenohypophysis
  • Marek Zak
  • Kaiman Kovacs
  • Donna J. McComb
  • Philipp U. Heitz


Thirty-six rats of both sexes in two groups were treated with aminoglutethimide (AG), a steroid synthesis inhibitor, for 1 and 8 weeks respectively. The anterior pituitaries were investigated by light and electron microscopy, the techniques used including immunocytochemical and morphometric methods. Corticotrophs were identified by the avidinbiotin-peroxidase complex technique at the light and electron microscopic levels. AG administration resulted in hyperplasia of ACTH-containing cells. The increase in the volume density of corticotrophs was prevented by simultaneous medication with 3 mg corticosterone in male rats, whereas in female rats a larger dose of corticosterone was required to suppress pituitary corticotroph hyperplasia. Electron microscopy revealed that in AG-treated rats, corticotrophs were larger and contained more secretory granules than those in controls, the mean secretory granule diameter increasing from 100 nm to 165 nm. Under AG stimulation, corticotrophs showed considerable variations in structural features probably reflecting differences in their functional state. It was apparent that only one ACTH-producing cell type existed in the pars distalis of the rat adenohypophysis, although this cell type may undergo substantial morphologic alterations due to changes in endocrine activity. Gonadotrophs and thyrotrophs showed morphologic signs of stimulation and exhibited hyperplasia following AG treatment indicating that the effect of the drug was not restricted to corticotrophs.

Key words

Anterior pituitary Aminoglutethimide Immunocytology Rats Ultrastructure 


  1. Baker BL, Pek S, Midgley AR Jr, Gersten BE (1970) Identification of the corticotropin cell in rat hypophyses with peroxidase labeled antibody. Anat Rec 166: 557–568PubMedCrossRefGoogle Scholar
  2. Bowie EP, Williams G, Shiino M, Rennels EG (1973) The corticotroph of the rat adenohypophysis: a comparative study. Am J Anat 138: 499–520PubMedCrossRefGoogle Scholar
  3. Bowie EP, Williams MG, Rennels EG (1974) Evidence for PAS positive reaction of the corticotroph granules of the rat adenohypophysis. Histochem 38: 281–284CrossRefGoogle Scholar
  4. Caselitz J, Saeger W (1979) The ultrastructure of the pituitary gland under chronic stimulation of the ACTH-cells in human pathology and animal experiments. Endokrinologie 74: 163–176PubMedGoogle Scholar
  5. Cash R, Brough AJ, Cohen MNP, Satoh PS (1967) Aminoglutethimide (Elipten-Ciba) as an inhibitor of adrenal steroidogenesis. Mechanism of action and therapeutic trial. J Clin Endocrinol Metab 27: 1239–1248PubMedGoogle Scholar
  6. Childs G, Unabia G (1982a) Application of the avidin-biotin-peroxidase complex (ABC) method to the light microscopic localization of pituitary hormones. J Histochem Cytochem 30: 713–716PubMedGoogle Scholar
  7. Childs G, Unabia G (1982 b) Application of a rapid avidin-biotin-peroxidase complex (ABC) technique to the localization of pituitary hormones at the electron microscopic level. J Histochem Cytochem 30: 1320–1324PubMedGoogle Scholar
  8. Daniels-Severs AE, Vernikos-Danellis J (1973) Effect of aminoglutethimide and glutethimide on the pituitary-adrenal system. Pharmacology 10: 111–122PubMedGoogle Scholar
  9. Dexter RN, Fishman LM, Ney RL, Liddle GW (1967) Inhibition of adrenal corticosteroid synthesis by aminoglutethimide. Studies of the mechanism of action. J Clin Endocrinol Metab 27: 473–480PubMedGoogle Scholar
  10. Emery FE, Winter CA (1934) The adrenotropic substance of the hypophysis as influenced by age, castration, sex and thyroparathyroidectomy. Anat Rec 60: 381–390CrossRefGoogle Scholar
  11. Farquhar MG (1957) “Corticotrophs” of the rat adenohypophysis as revealed by electron microscopy. Anat Rec [Abstr] 127: 291Google Scholar
  12. Gemzell CA, Van Dyke DC, Tobias CA, Evans HM (1951) Increase in the formation and secretion of ACTH following adrenalectomy. Endocrinology 49: 325–336PubMedGoogle Scholar
  13. Graves PE, Salhanick HA (1979) Seroselective inhibition of aromatase by enantiomers of aminoglutethimide. Endocrinology 105: 52–57PubMedGoogle Scholar
  14. Herlant M, Klastersky J (1963) Etude au microscope electronique des cellules corticotropes de l’hypophyse. CR Acad Sci 256: 2709–2711Google Scholar
  15. Kurosumi K, Kobayashi Y (1966) Corticotrophs in the anterior pituitary glands of normal and adrenalectomized rats as revealed by electron microscopy. Endocrinology 78: 745–758PubMedGoogle Scholar
  16. Marek J, Motlik K (1975) Ultrastructural changes of the adrenal cortex in Cushing’s syndrome treated with aminoglutethimide (Elipten Ciba). Virchows Arch [Cell Pathol] 18: 145–156Google Scholar
  17. Marek J, Motlik K (1978) Ultrastructure of acute adrenocortical damage due to aminoglutethimide (Elipten Ciba) in rats. Virchows Arch [Cell Pathol] 27: 173–187Google Scholar
  18. Moriarty GC, Halmi NS (1972) Electron microscopic study of the adrenocorticotropin cell with the use of unlabeled antibody and the soluble peroxidase-antiperoxidase complex. J Histochem Cytochem 20: 590–603PubMedGoogle Scholar
  19. Nakane PK (1970) Classifications of anterior pituitary cell types with immunoenzyme histochemistry. J Histochem Cytochem 18: 9–20PubMedGoogle Scholar
  20. Nakane PK (1971) Application of peroxidase-labeled antibodies to the intracellular localization of hormones. Acta Endocrinol 153: 190–204Google Scholar
  21. Nakayama I, Nickerson PA, Skelton FR (1969) An ultrastructural study of the adrenocorticotrophic hormone-secreting cell in the rat adenohypophyis during adrenal cortical regneration. Lab Invest 21: 169–178PubMedGoogle Scholar
  22. Nuesch H, Siebenmann R (1973) Die Wirkung von Aminoglutethimid auf die Zwischenzellen des Rattenhodens. Virchows Arch [Pathol Anat] 358: 149–162Google Scholar
  23. Pelletier G, Racadot J (1971) Identification des cellules hypophysaires secretant l’ACTH chez le rat. Z Zellforsch 116: 228–239PubMedCrossRefGoogle Scholar
  24. Pittman JA, Brown RW (1966) Antithyroid and antiadrenocorticoid activity of aminoglutethimide. J Clin Endocrinol Metab 26: 1014–1016PubMedGoogle Scholar
  25. Rennels EG, Shiino M (1968) Ultrastructural manifestations of pituitary release of ACTH in the rat. Arch Anat [Strasbourg] 51: 575–590Google Scholar
  26. Saeger W (1974) Ultrastruktur der gonadotropen Zellen der Rattenhypophyse nach Gabe antiandrogener Substanzen. Virchows Arch [Pathol Anat] 363: 47–64CrossRefGoogle Scholar
  27. Saeger W, Caselitz J (1974) Zur Ultrastruktur der ACTH-Zellen in der Rattenhypophyse nach Gabe von Adrenostatika und Methylprednisolon. Virchows Arch [Pathol Anat] 364: 199–214CrossRefGoogle Scholar
  28. Santen RJ, Lipton A, Kendall J (1974) Successful medical adrenalectomy with aminoglutethimide. Role of altered drug metabolism. J Am Med Assoc 230: 1661–1665CrossRefGoogle Scholar
  29. Siperstein ER (1963) Identificiation of the adrenalcorticotrophin-producing cells in the rat hypophysis by autoradiography. J Cell Biol 17: 521–546PubMedCrossRefGoogle Scholar
  30. Siperstein ER, Allison VF (1965) Fine structure of the cells responsible for secretion of adrenocorticotrophin in the adrenalectomized rat. Endocrinology 76: 70–79PubMedCrossRefGoogle Scholar
  31. Siperstein ER, Miller KJ (1970) Further cytophysiological evidence for the identity of the cells that produce adrenocorticotrophic hormone. Endocrinology 86: 451–486PubMedCrossRefGoogle Scholar
  32. Sydnor KL, Sayers G (1954) Blood and pituitary ACTH in intact and adrenalectomized rats after stress. Endocrinology 55: 621–636PubMedGoogle Scholar
  33. Yoshimura F, Nogami H (1981) Fine structural criteria for identifying rat corticotrophs. Cell Tissue Res 219: 221–228PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Marek Zak
    • 1
    • 2
  • Kaiman Kovacs
    • 1
    • 2
  • Donna J. McComb
    • 1
    • 2
  • Philipp U. Heitz
    • 1
    • 2
  1. 1.Department of Pathology, St. Michael’s HospitalUniversity of TorontoTorontoCanada
  2. 2.Department of PathologyUniversity of BaselBaselSwitzerland

Personalised recommendations