Author Institution: The Ohio State Universit

Baker, Rollo C.

Edwards, Linden F.

The Ohio Journal of Science

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EARLY DEVELOPMENT OF THE HUMAN PHARYNGEALHYPOPHYSIS — A PRELIMINARY REPORT1ROLLO C. BAKER AND LINDEN F. EDWARDS,The Ohio State UniversityMost textbooks of Embryology and of Histology generally agree on the followingmore or less well-known facts: (1) the hypophysis or pituitary gland occupies adepression (the hypophyseal fossa) within the sella turcica which is located on thecranial aspect of the body of the sphenoid bone; (2) the hypophysis is a compositeorgan consisting of two main portions, an anterior and a posterior; (3) the anteriorportion is further divisible into the pars distalis (or anterior lobe proper), the parstuberalis and the pars intermedia, the posterior portion being designated usuallyas the neural lobe or pars neuralis; (4) three types of cells are recognizable in theanterior lobe; namely chromophobes, or reserve cells, which lack secretory granules,acidophiles, which contain alpha or acidophilic granules and basophiles, so-calledbecause they contain beta or basophilic secretory granules; (5) the pars anterioris derived from the distal closed end of Rathke's pouch and the pars posteriorarises from the infundibulum of the hypothalamic region of the diencephalon;(6) Rathke's pouch develops as a hollow epithelial diverticulum from the roof ofthe embryonic oral cavity or stomodaeum; (7) the original point of union ofRathke's pouch with the oral epithelium comes to be located well back on the roofof the primitive mouth, and still later when the palate separates off the nasalfossae from the oral cavity proper its site of origin lies at the postero-superiorborder of the nasal septum at its junction with the roof of the nasal pharynx; and(8) the distal end or hypophyseal portion of Rathke's pouch becomes separatedfrom the stomodaeal epithelium by the obliteration of its original connecting ductor stalk.Obliteration of the proximal connecting portion of Rathke's pouch with theoral epithelium is a gradual process. When the para-axial mesenchyme differen-tiates into embryonic connective tissue in the region of the future body of thesphenoid bone the connection of Rathke's pouch with its site of implantation tothe epithelium becomes elongated and is gradually reduced to a narrow duct orstalk, which is termed the hypophyseal stalk or craniopharyngeal canal. When,later on, the process of chondrification takes place in the connective tissue, by meansof which the cartilaginous body of the sphenoid is formed, the pharyngeal stalkis gradually compressed into a slender epithelial strand which is said to normallydegenerate and disappear.Most textbooks of embryology fail to give much detail concerning the originand fate of Rathke's pouch and they dismiss the subject usually by merely statingthat the stalk by which Rathke's pouch was attached to the stomodael epitheliumcompletely disappears (2, 6, 10, 13, 14, 17, 18, 19, 21). On the other hand, someauthors mention the occasional persistence of remnants of the connecting stalk ofRathke's pouch (1, 4, 7, 8, 11, 22, 24). Three typical sites of locations of theseremnants have been described, namely "intracranial"—within the hypophysealfossa adjacent to the hypophysis but separated from it by cranial dura mater,"interosseous"—embedded within the body of the sphenoid bone, and "phar-yngeal"—within the soft tissue in the roof of the nasal pharynx. The term "phar-yngeal hypophysis" is applied to the epithelial remnant in the roof of the nasal1This investigation was aided by a grant from the Ohio State University DevelopmentFund, for which the authors make grateful acknowledgment.241242 ROLLO C. BAKER AND LINDEN F. EDWARDS Vol. X L V I I Ipharynx as opposed to the other two which are usually considered as a "persistentcraniopharyngeal canal" (8, 22).These epithelial remnants are generally considered to be anomalies or abnor-malities. However, a few authors point out that the pharyngeal hypophysis issaid to be constantly present (1, 4, 7, 22, 24). Thus, according to Smith andCopenhaver (24) "There occurs constantly in the vault of the nasopharynx, inman, a body of typical anterior lobe tissue. It has not been demonstrated in otherspecies. This body lies in the midline and is elongated, its longitudinal axis beingparallel to the sagittal plane of the body. It measures from 3.5 to 7 mm. in lengthby 1 mm. or less in diameter. The cells of the pharyngeal hypophysis are struc-turally identical with those of the anterior lobe and parallel them in theirdifferentiation and development."In view of the general agreement, among these outstanding embryologists andhistologists, as to the constancy of occurrence of the pharyngeal hypophysis itseems strange that it is so frequently ignored in many textbooks of embryology,histology and human anatomy and that studies on its frequency of occurrence inthe vertebrate series and on its histogenesis in man and other species have beenso generally neglected. Aside from scattered reports in the literature concerningits involvement in neoplastic growths, which would appear very likely, surprisinglyfew papers bearing on its frequency in man and lower animals and on detail studiesof its development have appeared. Haberfeld (9) reported the results of his studieson its development in a few human fetuses including the newborn; Christeller (5)reported its normal and pathological appearance in adults and in 1938 there ap-peared for the first time in the English literature a report of its occurrence in humanautopsy material. This was by Melchionna and Moore (20) who found it in 51out of 53 unselected autopsied bodies which they studied, ranging in age from thenewborn to 69 years. These authors claimed its cellular constituents were histo-logically identical with those in the pars anterior of the hypophysis except thedifferentiated cells were relatively fewer. Hertwig (11) claimed that in manyvertebrates, e.g. Selachians, the pharyngeal stalk is retained throughout life as ahollow canal which perforates the base of the skull and is united with the oralepithelium. Kingsbury (15, 16) made a detail study of it in the dog in which heclaimed it occurred in almost 100% of the cases examined and mentioned that ithad been reported seen in the cat (3) and rabbit. Its presence in the rat (23) andox (12) however, has been denied.Inasmuch as so few studies have been made of this structure, and in viewof its possible involvement in pathological conditions of the hypophysis and possiblyother endocrine organs, the authors have launched upon a research program toinvestigate its frequency of appearance in man and other vertebrates, its histo-genesis and fate and eventually to determine whether or not pathological conditionsor experimental procedures may affect it in any way. The present report on itsearly development in man is the first to come out of this projected study.In a six mm. (about four weeks) human embryo Rathke's pouch is well defined(Fig. A). It appears in a sagittal section as a finger-like epithelial diverticulumin close relation to the floor of the fore-brain and with a narrow, slit-like lumenopening inferiorly into the oral cavity. However, in a transverse section at thisstage it is, in reality, wide and flattened.By the 12 mm. stage (about five weeks) the continuity of Rathke's pouchthroughout its length is broken, its distal free end, which is destined to differentiateinto the pars anterior of the hypophysis, is enlarged and its proximal end persistsfor some distance and retains its connection with the oral epithelium (Fig. B).Condensation of the mesenchyme in the area intervening between the remainingportions of Rathke's pouch (4 and 5) indicates the beginning of chondrification ofthe future body of the sphenoid and may explain the constriction of the neck of theDevelopment of the Pharyngeal HypophysisRollo C. Baker and Linden F. EdwardsPLATE IPhotomicrographs of sections of human embryos showing stages in developmentof the pharyngeal hypophysis.A. 6 mm. Human—Sagittal section—Mag. 84X—H. & E.B. 12 mm. Human—Sagittal section—Mag. 81X— H. & E.C. 22 mm. Human—Cross section —Mag. 387X—H. & E.D. 25 mm. Human—Sagittal section—Mag. 44X—H. & E.E. 50 mm. Human—Sagittal section—Mag. 778X—H. & E.F. 80 mm. Human—Sagittal section—Mag. 84X—Hem. & Orange G.1. Rathke's pouch. 5. Pars anterior of hypophysis.2. Oral cavity. 6. Nasal pharynx.3. Fore-brain. 7. Infundibulum.4. Pharyngeal hypophysis. 8. Basi-sphenoid.243244 ROLLO C. BAKER AND LINDEN F. EDWARDS Vol. X L V I I Ipouch. The persistent site of implantation of the proximal end of the pouch is theprimordium of the pharyngeal hypophysis.Figure C shows a magnification of the pharyngeal hypophysis (4) in a 22 mm.(about eight weeks) human embryo. The epithelial cells composing it are un-differentiated, although they exhibit evidence of elongation and proliferation atthe site of implantation on the free surface of the oral epithelium. The persistentstalk is- surrounded by mesenchyme with the exception of its periphery where aconnective tissue capsule is differentiating and an embryonic blood vessel is makingits appearance at its free distal extremity.In an embryo 25 mm. in length (about 10 weeks) the future body of the sphenoidis cartilaginous, the sella turcica is outlined and is occupied by the future hypophy-sis, the pars anterior of which shows vesicle-formation, and the pharyngeal hypo-physis is well marked and distinguishable from the surrounding cells, its originaldirection with respect to the differentiating pars anterior of the hypophysis beingmaintained. By this stage the palate has formed and the original site of attachmentof the pharyngeal hypophysis to the epithelium of the primitive, oral cavity hasshifted caudally (rather the head has grown forward from that point) so that itnow lies in the roof of the nasal pharynx, where its presence has been described inthe adult stage (5, 9, 20).No evidence could be found in the present series of human embryos of thebeginning of cellular differentiation in either the future hypophysis or the pharyh-geal hypophysis until the 50 mm. stage (about 12 weeks), at which time (Fig. E)the cellular constituents of both (4, 5) were almost identical and consisted of twotypes, one type having an oval, vesicular nucleus with relatively sparse, more orless colorless cytoplasm and the other type having a smaller, rounder and moredarkly staining nucleus with more abundant, and slightly acidophilic, cytoplasm.The oldest human embryo included in the present study was an 80 mm. (about14 weeks) stage (Fig. F). As can readily be seen from the photomicrograph thepharyngeal hypophysis is well marked and, in comparison with previous stages,has undergone considerable hypertrophy and is quite vascular when examinedunder high magnification. Cellular differentiation in the pars anterior and in thepharyngeal hypophysis showed little advancement over the 50 mm. stage. Acursory examination of stages 115 mm. (about 4 months), 138 mm.(about 4 ^months) and 160 mm. (about 5 months) revealed its presence and to be undergoingcontinued hypertrophy and increased vascularity.Further studies of the fate of the pharyngeal hypophysis in older human embryosare in progress and will be reported in the future.REFERENCES(1) Arey, L, B. Developmental Anatomy. W. B. Saunders Company, Philadelphia, Fifthedition, 1947, p. 205.(2) Bailey, F. R., and Miller, A. M. Text-book of Embryology. William Wood and Company,New York. Second edition, 1911, p. 538.(3) Brahms, S. The development of the hypophysis of the Cat (Felis domestica). Am. Jour-Anat. 50: 251-281, 1932.(4) Bremer, J. L., and Weatherford, H, L. A Text-book of Histology. The Blakiston Com-pany, Philadelphia, sixth edition of Lewis and Stohr, 1944, p. 419.(5) Christeller, E. Die Rachendachhypophyse des menschen unter normalen und pathologischenVerhaltnissen. Virchow's Arch. f. path. Anat. 218: 185-223, 1914.(6) Dodds, G. S. The essentials of Human Embryology. John Wiley and Sons, Inc., NewYork, second edition, 1938, p. 136.(7) Frazer, J. E. A Manual of Embryology. Bailtiere, Tindall and Cox, London, 1940, p. 286.(8) Gudernatsch, J. F. The glands of Internal Secretion. In Morris' Human Anatomy,edited by J. Parsons Schaeffer. The Blakiston Company, Philadelphia, tenth edition,1942, p. 1511.(9) Haberfeld, W. Die Rachendachhypophyse, andere Hypophysengangreste, und derenBedentung fur die Pathologic Beitrage z. path. Anat. u. z. Allg. Path. 46: 133-232,1909.N o . 6 DEVELOPMENT OF THE PHARYNGEAL HYPOPHYSIS 245(10) Hamilton, W. J., Boyd, J. D., and Mossman, H. W. Human Embryology. Williamsand Wilkins Company, Baltimore, 1945, p. 253.(11) Hertwig, O. Text-book of the Embryology of Man and Mammals. Translated fromthe third German edition by E. L. Mark, The Macmillan Company, New York, 1892,p. 437.(12) House, E. L. The development of the hypophysis of the Ox. Am. Jour. Anat. 73: 1-24,1943.(13) Jordan, H. E., and Kindred, J. E. A Text-book of Embryology. D. Appleton and Com-pany, New York, fourth edition, 1942.(14) Keibel, F., and Mall, F. P. Manual of Human Embryology. J. B. Lippincott Company,Philadelphia, 1910.(15) Kingsbury, B. F. The pharyngeal hypophysis of the dog. Anat. Rec. 82: 39-55, 1942.(16) Kingsbury, B. F., and Roemer, F. J. The development of the hypophysis of the dog.Am. Jour. Anat. 66: 449-476, 1944.(17) Krafka, J. Human Embryology. Paul B. Hoeber, Inc., New York, 1942, p. 169.(18) Maximow, A. A., and Bloom, W. A Text-book of Histology. W. B. Saunders Company,Philadelphia, fourth edition, 1942, p. 309.(19) McMurrich, J. P. The Development of the Human Body. The Blakiston Company,Philadelphia, seventh edition, 1923, p. 404.(20) Melchionna, R. H., and Moore, R. A. The Pharyngeal Pituitary Gland. Am. Jour.Path. 14: 763-771, 1938.(21) Minot, C. S. A Laboratory Text-book of Embryology. The Blakiston Company, Phila-delphia, 1903, p. 207.(22) Patten, B. M. Human Embryology. The Blakiston Company, Philadelphia, 1946,p. 528.(23) Schwind, J. L. The development of the hypophysis cerebri of the Albino rat. Am. Jour.Anat. 41: 295-319, 1928.(24) Smith, P. E., and Copenhaver, W. M. Bailey's Text-book of Histology. Williams andWilkins Company, Baltimore, eleventh edition, 1944, p. 657.

Early Development of the Human Pharyngeal Hypophysis--A Preliminary Report

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Early Development of the Human Pharyngeal Hypophysis--A Preliminary Report

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