Anatomy and Embryology

, Volume 191, Issue 2, pp 139–143

Early expression of chromogranin A and tyrosine hydroxylase during prenatal development of the bovine adrenal gland

  • Ines Totzauer
  • Werner Amselgruber
  • Fred Sinowatz
  • Manfred Gratzl
Original Article


The present study was undertaken to define the temporal pattern and distribution of cells positive for chromogranin A (CgA) and tyrosine hydroxylase (TH) in various developmental stages of fetal bovine adrenal gland. CgA is an acidic protein, co-stored and co-released with amines and a variety of peptide hormones and neurotransmitters in dense core vesicles of neural and endocrine cells and can be used as a marker for these cells and their malignant counterparts. TH is the rate-limiting enzyme in catecholamine biosynthesis and reflects noradrenergic differentiation. The expression of CgA and TH was examined by immunohistochemistry. CgA immunoreactivity appears first in 35-day-old bovine fetuses. By the end of the second month, CgA-labelled cells are scattered throughout the entire primordium of the adrenal gland, and at a fetal age of 85–91 days most of these cells concentrate in the developing adrenal medulla. From this stage onwards, immunoreactive cells of the marginal zone of the medulla exhibit significantly stronger CgA immunoreaction than the central area. TH immunoreactivity appeared in the adrenal primordium for the first time at the end of the second month of gestation. The distribution pattern of TH-positive cells was similar to that described for CgA, and no significant differences in topographical arrangement between TH- and CgA-positive cells can be detected. The results show that bovine adrenal chromaffin cells express CgA already during their earliest stages of development and prior to TH. The stronger immunoreaction of marginal adrenal medullary cells suggests an adrenalcortical effect of glucocorticoids on the expression of CgA.

Key words

Chromogranin A Tyrosine hydroxylase Development Adrenal gland Bovine fetus 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Banks P, Helle K (1965) The release of protein from the stimulated adrenal medulla. Biochem J 97:40cGoogle Scholar
  2. Benedum UM, Bauerle PA, Konecki DS, Frank R, Powell J, Mallet J, Huttner B (1986) The primary structure of bovine chromogranin A: a representative of a class of acidic secretory proteins common to a variety of peptidergic cells. EMBO J 5:1495–1502Google Scholar
  3. Bohn MC, Goldstein M, Black I (1981) Role of glucorticoids in expression of the adrenergic phenotype in rat embryonic adrenal gland. Dev Biol 82:1–10Google Scholar
  4. Cochard P, Goldstein M, Black I (1978) Ontogenetic appearance and disappearance of tyrosine hydroxylase and catecholamines in the rat embryo. Proc Natl Acad Sci USA 75:2986–2990Google Scholar
  5. Deftos LJ (1991) Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocrinol Rev 12:181–187Google Scholar
  6. Eiden LE (1987) Is chromogranin a prohormone? Nature 325:301Google Scholar
  7. Erhart M, Grube D, Bader M, Aunis D, Gratzl M (1986) Chromogranin A in the pancreatic islet: cellular and subcellular distribution. J Histochem Cytochem 34:1673–1682Google Scholar
  8. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. Histochem Cytochem 29:577–580Google Scholar
  9. Kent C, Coupland RE (1989) Localization of chromogranin A and B, met-enkephalin-arg-gly-leu and PGP9. 5-like immunoreactivity in the developing and adult rat adrenal medulla and extra-adrenal chromaffin tissue. J Anat 166:213–225Google Scholar
  10. Molenaar WS, Lee VMY, Trojanowski JQ (1990) Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins. Exp Neurol 108:1–9Google Scholar
  11. Murakami T, Oukouchi H, Uno Y, Ohtsuka A, Taguci T (1989) Blood vascular beds of rat adrenal and accessory glands, with special reference to the corticomedullary portal system: a further scanning electron microscopic study of corrosion casts and tissue specimens. Arch Histol Cytol 52:461–476Google Scholar
  12. Reiffen FU, Gratzl M (1986a) Chromogranins, widespread in endocrine and nervous tissue, bind Ca++. FEBS Lett 195:327Google Scholar
  13. Reiffen FU, Gratzl M (1986b) Ca2+-binding to chromaffin vesicle matrix proteins: effect of pH, Mg2+ and ionic strength. Biochemistry 25:4402Google Scholar
  14. Rohrer H, Acheson AL, Thibault J, Thoenen H (1986) Developmental potential of quail dorsal root ganglion cells analyzed in vitro and in vitro. J Neurosci 6:2616–2624Google Scholar
  15. Romeis B (1989) Nebennieren und chromaffines Gewebe. In: Mikroskopische Technik, 17. Urban & Schwarzenberg, München Wien Baltimore, pp 621–623Google Scholar
  16. Seidl K, Unsicker K (1989) The determination of the adrenal medullary cell fate during embryogenesis. Dev Biol 136:481–490Google Scholar
  17. Sternberger LA (1986) Immunohistochemistry, 3rd edn. Wiley, New YorkGoogle Scholar
  18. Winkler H, Fischer-Colbrie R (1992) The chromogranins A and B: the first 25 years and future perspectives. Neuroscience 49:497–528Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Ines Totzauer
    • 1
  • Werner Amselgruber
    • 1
  • Fred Sinowatz
    • 1
  • Manfred Gratzl
    • 2
  1. 1.Institut für Tieranatomie II, Universität MünchenMünchenGermany
  2. 2.Abteilung Anatomie und Zellbiologie, Universität UlmUlmGermany

Personalised recommendations