Skip to main content
Log in

Aminoglutethimide-stimulated corticotrophs

An immunocytologic, ultrastructural and immunoelectron microscopic study of the rat adenohypophysis

  • Published:
Virchows Archiv B

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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: 557–568

    Article  PubMed  CAS  Google Scholar 

  • Bowie EP, Williams G, Shiino M, Rennels EG (1973) The corticotroph of the rat adenohypophysis: a comparative study. Am J Anat 138: 499–520

    Article  PubMed  CAS  Google Scholar 

  • Bowie EP, Williams MG, Rennels EG (1974) Evidence for PAS positive reaction of the corticotroph granules of the rat adenohypophysis. Histochem 38: 281–284

    Article  CAS  Google Scholar 

  • 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: 163–176

    PubMed  CAS  Google Scholar 

  • 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: 1239–1248

    PubMed  CAS  Google Scholar 

  • 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: 713–716

    PubMed  CAS  Google Scholar 

  • 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: 1320–1324

    PubMed  CAS  Google Scholar 

  • Daniels-Severs AE, Vernikos-Danellis J (1973) Effect of aminoglutethimide and glutethimide on the pituitary-adrenal system. Pharmacology 10: 111–122

    PubMed  CAS  Google Scholar 

  • 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: 473–480

    PubMed  CAS  Google Scholar 

  • Emery FE, Winter CA (1934) The adrenotropic substance of the hypophysis as influenced by age, castration, sex and thyroparathyroidectomy. Anat Rec 60: 381–390

    Article  CAS  Google Scholar 

  • Farquhar MG (1957) “Corticotrophs” of the rat adenohypophysis as revealed by electron microscopy. Anat Rec [Abstr] 127: 291

    Google Scholar 

  • Gemzell CA, Van Dyke DC, Tobias CA, Evans HM (1951) Increase in the formation and secretion of ACTH following adrenalectomy. Endocrinology 49: 325–336

    PubMed  CAS  Google Scholar 

  • Graves PE, Salhanick HA (1979) Seroselective inhibition of aromatase by enantiomers of aminoglutethimide. Endocrinology 105: 52–57

    PubMed  CAS  Google Scholar 

  • Herlant M, Klastersky J (1963) Etude au microscope electronique des cellules corticotropes de l’hypophyse. CR Acad Sci 256: 2709–2711

    CAS  Google Scholar 

  • Kurosumi K, Kobayashi Y (1966) Corticotrophs in the anterior pituitary glands of normal and adrenalectomized rats as revealed by electron microscopy. Endocrinology 78: 745–758

    PubMed  CAS  Google Scholar 

  • 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: 145–156

    CAS  Google Scholar 

  • Marek J, Motlik K (1978) Ultrastructure of acute adrenocortical damage due to aminoglutethimide (Elipten Ciba) in rats. Virchows Arch [Cell Pathol] 27: 173–187

    CAS  Google Scholar 

  • 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: 590–603

    PubMed  CAS  Google Scholar 

  • Nakane PK (1970) Classifications of anterior pituitary cell types with immunoenzyme histochemistry. J Histochem Cytochem 18: 9–20

    PubMed  CAS  Google Scholar 

  • Nakane PK (1971) Application of peroxidase-labeled antibodies to the intracellular localization of hormones. Acta Endocrinol 153: 190–204

    CAS  Google Scholar 

  • 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: 169–178

    PubMed  CAS  Google Scholar 

  • Nuesch H, Siebenmann R (1973) Die Wirkung von Aminoglutethimid auf die Zwischenzellen des Rattenhodens. Virchows Arch [Pathol Anat] 358: 149–162

    CAS  Google Scholar 

  • Pelletier G, Racadot J (1971) Identification des cellules hypophysaires secretant l’ACTH chez le rat. Z Zellforsch 116: 228–239

    Article  PubMed  Google Scholar 

  • Pittman JA, Brown RW (1966) Antithyroid and antiadrenocorticoid activity of aminoglutethimide. J Clin Endocrinol Metab 26: 1014–1016

    PubMed  CAS  Google Scholar 

  • Rennels EG, Shiino M (1968) Ultrastructural manifestations of pituitary release of ACTH in the rat. Arch Anat [Strasbourg] 51: 575–590

    Google Scholar 

  • Saeger W (1974) Ultrastruktur der gonadotropen Zellen der Rattenhypophyse nach Gabe antiandrogener Substanzen. Virchows Arch [Pathol Anat] 363: 47–64

    Article  CAS  Google Scholar 

  • Saeger W, Caselitz J (1974) Zur Ultrastruktur der ACTH-Zellen in der Rattenhypophyse nach Gabe von Adrenostatika und Methylprednisolon. Virchows Arch [Pathol Anat] 364: 199–214

    Article  CAS  Google Scholar 

  • Santen RJ, Lipton A, Kendall J (1974) Successful medical adrenalectomy with aminoglutethimide. Role of altered drug metabolism. J Am Med Assoc 230: 1661–1665

    Article  CAS  Google Scholar 

  • Siperstein ER (1963) Identificiation of the adrenalcorticotrophin-producing cells in the rat hypophysis by autoradiography. J Cell Biol 17: 521–546

    Article  PubMed  CAS  Google Scholar 

  • Siperstein ER, Allison VF (1965) Fine structure of the cells responsible for secretion of adrenocorticotrophin in the adrenalectomized rat. Endocrinology 76: 70–79

    Article  PubMed  CAS  Google Scholar 

  • Siperstein ER, Miller KJ (1970) Further cytophysiological evidence for the identity of the cells that produce adrenocorticotrophic hormone. Endocrinology 86: 451–486

    Article  PubMed  CAS  Google Scholar 

  • Sydnor KL, Sayers G (1954) Blood and pituitary ACTH in intact and adrenalectomized rats after stress. Endocrinology 55: 621–636

    PubMed  CAS  Google Scholar 

  • Yoshimura F, Nogami H (1981) Fine structural criteria for identifying rat corticotrophs. Cell Tissue Res 219: 221–228

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zak, M., Kovacs, K., McComb, D.J. et al. Aminoglutethimide-stimulated corticotrophs. Virchows Archiv B Cell Pathol 49, 93–106 (1985). https://doi.org/10.1007/BF02912088

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02912088

Key words

Navigation