Anatomy and Embryology

, Volume 178, Issue 4, pp 327–336 | Cite as

The development and morphogenesis of the human pituitary gland

  • Hidetoshi Ikeda
  • Jiro Suzuki
  • Nobuaki Sasano
  • Hiroshi Niizuma


In order to clarify the environmental factors which are involved in the development of the primordium of the pituitary gland such as cell-cell interactions, a three-dimensional reconstruction of this organ and its surrounding tissues was carried out. Pituitary material was obtained from human fetuses mainly during the period of organogenesis. Rathke's diverticulum was found to stretch rostrally from the stomodeal epithelium to the middle of the mesoderm, and already by the 5th week of fetal growth, it was clearly seen to be involved with the diencephalon. The area of contact between Rathke's pouch and the diencephalon gradually moved from the rostral to caudal regions and, after 13 weeks of development, had a position similar to that found in the newborn infant.

Among the cells forming Rathke's pouch, it was found that the closer their relationship was to the diencephalon, the greater were their epithelial characteristics. When the relationship of such cells to the diencephalon was weaker, their differentiation to endocrine cells occurred earlier. Immunohistochemically, that portion of the pituitary primordium which has a close relationship with the diencephalon, later to become the pars intermedia, showed an adrenocorticotropic hormone (ACTH) immunoreactivity later than that of the pars anterior. On the other hand, in the 21st fetal week, nearly all of the cells of the pars intermedia were found to be ACTH-positive. This finding is thought to indicate a close connection between the physical contact between the brai (diencephalon) and the pituitary primordium and the development of the pars intermedia; the differentiation of ACTH cells. The surface of the epithelium of Rathke's cavity continues to increase at least until the 21st fetal week, so the growth of the epithelium of Rathke's pouch is thought to be heavily involved in the growth of the primordium of the pituitary gland in the early stages of development.

Key words

Pituitary gland Immunohistochemistry Three-dimensional reconstruction Rathke's pouch 


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  1. Asa SL, Kovacs K, Laszlo FA, Domokos I, Ezrin C (1986) Human fetal adenohypophysis. Neuroendocrinology 43:308–316Google Scholar
  2. Atwell WJ (1926) The development of the hypophysis cerebri in man, with special reference to the pars tuberalis. Am J Anat 37:159–193Google Scholar
  3. Atwell WJ (1939) The morphogenesis of the hypophysis cerebri of the domestic fowl during the second and third weeks of incubation. Anat Rec 73:57–71Google Scholar
  4. Baker BL, Jaffe RB (1975) The genesis of cell types in the adenohypophysis of the human fetus as observed with immunocytochemistry. Am J Anat 143:137–162Google Scholar
  5. Begeot M, Dubois MP, Dubois PM (1977) Growth hormone and ACTH in the pituitary of normal and anencephalic human fetuses: Immunocytochemical evidence for hypothalamic influences during development. Neuroendocrinology 24:208–220Google Scholar
  6. Ciocca DR, Puy LA, Stati AO (1985) Identification of seven hormone-producing cell types in the human pharyngeal hypophysis. J Clin Endocrinol Metab 60:212–215Google Scholar
  7. Conklin JL (1968) The development of the human fetal adenohypophysis. Anat Rec 160:79–92Google Scholar
  8. Daikoku S (1958) Studies on the human foetal pituitary. Tokushima J Exp Med 5:214–231Google Scholar
  9. Daikoku S, Kawano H, Abe K, Yoshinaga K (1981) Topographical appearance of adenohypophysial cells with special reference to the development of the portal system. Arch Histol Jpn 44:103–116Google Scholar
  10. Daikoku S (1986) Development of the hypothalamic-hypophysial axis in rats. In: Yoshimura F, Gorbman (ed) Pars distalis of the pituitary gland. Elsevier, Amsterdam, pp 21–27Google Scholar
  11. Dubois P, Vargues-Regairaz H, Dubois MP (1973) Human foetal anterior pituitary immunofluorescent evidence for corticotropin and melanotropin activities. Z Zellforsch Mikrosk Anat 145:131–143Google Scholar
  12. Friedman B (1934) The mesodermal relations of the pars buccalis of the hypophysis in the duck. J Morphol 55:611–631Google Scholar
  13. Fujita S (1960) Mitotic pattern and histogenesis of the central nervous system. Nature 185:702–703Google Scholar
  14. Gibert MS (1935) Some factors influencing the early development of the mammalian hypophysis. Anat Rec 62:337–357Google Scholar
  15. Green JD (1951) The comparative anatomy of the hypophysis, with special reference to its blood supply and innervation. Am J Anat 88:225–312Google Scholar
  16. Grobstein C (1953) Morphogenetic interaction between embryonic mouse tissues separated by a membrane filter. Nature 172:869–870Google Scholar
  17. Hamilton WJ, Mossman HW (1972) Growth of the embryo and fetus; Development of external form; Estimation of embryonic and fetal age. In: Human Embryology: Chapter 8, Hefter W & Sons, Cambridge, pp 174–191Google Scholar
  18. Hsu SM, Raine L, Fanger H (1981) Use of avidine-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580Google Scholar
  19. Kraicer J (1976) Lack of release of ACTH from the denervated rat pars intermedia in vivo. Can J Physiol Pharmacol 54:809–813Google Scholar
  20. Kusakabe M, Sakakura T, Sano M, Nishizuka Y (1986) Epithelialmesenchymal interaction in early development of the mouse pituitary gland. In: Yoshimura F, Gorbman A (ed) Pars distalis of the pituitary gland. Elsevier, Amsterdam, pp 15–16Google Scholar
  21. Leatherland JF, Renfree MB (1982) Ultrastructure of the nongranulated cells and morphology of the extracellular spaces in the pars distalis of adult and pouch-young tammer wallabies. Cell Tissue Res 227:439–450Google Scholar
  22. Ludel E (1918) Formentwicklung der menschlichen Hypophysis cerebri. Anat Hefte 55:187–225Google Scholar
  23. Mcgrath P (1978) Aspects of the human pharyngeal hypophysis in normal and anencephalic fetus and neonate and their possible significance in the mechanism of its control. Anat 127:65–81Google Scholar
  24. Macphie JL, Beck JS (1973) The histological features and human growth hormone content of the pharyngeal pituitary gland in normal and endocrinologically-disturbed patients. Clin Endocrinol 2:157–173Google Scholar
  25. Mihalkivics V (1875) Wirbelsaite und hirnanhang. Arch Mikrosk Anat 11:388–441Google Scholar
  26. Moriarty GC, Halmi NS, Moriarty CM (1975) The effect of stress on the cytology and immunocytochemistry of pars intermedia cells in the rat pituitary. Endocrinol 96:1426–1436Google Scholar
  27. Nishimura H, Takano K, Tanimura T, Yasuda M (1968) Normal and abnormal development of human embryos: First report of the analysis of 1213 intact embryos. Teratology 1:281–290Google Scholar
  28. Nishimura H, Tanimura T, Semba R, Uwabe C (1974) Normal development of early human embryos: Observation of 90 specimens at Carniegie stages 7 to 13. Teratology 10:1–8Google Scholar
  29. Ohtsuka Y, Ishikawa H, Omoto T, Takasaki Y, Yoshimura F (1971) Effect of CRF on the morphological and functional differentiation of the cultured chromophobes isolated from rat anterior pituitaries. Endocrinol Jpn 18:133–153Google Scholar
  30. Painter BT (1942) Studies of avian pituitary. Anat Rec 84:387–400Google Scholar
  31. Phifer RF, Orth DN, Spicer SS (1974) Specific demonstration of the human hypophyseal adrenocortico-melanotropic (ACTH/MSH) cells. J Clin Endocrinol Metabol 39:684–692Google Scholar
  32. Rathke H (1938) Über die Entstehung der Glandula pituitaria. Arch Anat Physiol Wissensch Med 5:482–485Google Scholar
  33. Rahn H (1939) The development of the chick pituitary with special reference to the cellular differentiation of the pars buccalis. J Morphol 64:483–517Google Scholar
  34. Rinne UK (1963) Neurosecretary material passing into the hypophyseal portal system in the human infundibulum, and its fetal development. Acta Neuroveg 25:310–324Google Scholar
  35. Saxen L, Ekblom P, Thesleff I (1980) Development in mammals. In: Johnson MH (ed). Elsevier, Amsterdam, pp 161–169Google Scholar
  36. Shanklin WM (1951) The incidence and distribution of cilia in the human pituitary with a description of micro-follicular cysts derived from Rathke's cleft. Acta Anatomica 11:361–382Google Scholar
  37. Streeter GL (1948) Developmental horizons in human embryos: Description of age group XV, XVI, XVII, and XVIII. Contrib Embryol 32:133–203Google Scholar
  38. Takahashi T, Iwama N (1984) Atypical glands in gastric adenoma. Virchows Arch [A] 403:135–148Google Scholar
  39. Tilney F (1913) An analysis of the juxtaneural elements of the pituitary. Int Monatsch Anat Physiol 30:258–293Google Scholar
  40. Vila-Porcile W (1972) Le résau des cellules folliculostéllaires et les follicles de ládenohypophyse du rat (pars distalis). Z Zellforsch 129:328–369Google Scholar
  41. Waterstone D (1926) The development of the hypophysis cerebri in man, with a note upon its structure in the human adult. Transl R Soc Edin 55:125–143Google Scholar
  42. Yoshimura F, Soji T, Kiguchi Y (1977) Relationship between the follicular cells and marginal layer cells of the anterior pituitary. Endocrinol Jpn 24:301–305Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Hidetoshi Ikeda
    • 1
  • Jiro Suzuki
    • 1
  • Nobuaki Sasano
    • 2
  • Hiroshi Niizuma
    • 1
  1. 1.Division of Neurosurgery, Institute of Brain DiseasesTohoku University School of MedicineSendaiJapan
  2. 2.Department of PathologyTohoku University School of MedicineSendaiJapan

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