The Fine Structure of the Parathyroid Gland

25 Pages·2003·2.01 MB·English

The Fine Structure of the Parathyroid Gland*
BY JERRY STEVEN TRIER, M.D.
(From eht Department of Anatomy, University of School Washington of Medicine, )elttaeS
SETALP 3 OT 01
(Received for publication, July 29, 1957)
ABSTRACT
The fine structure of the parathyroid of the macaque is described, and is cor-
related with classical parathyroid cytology as seen in the light microscope. D
o
The two parenchymal cell types, the chief cells and the oxyphil cells, have wn
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been recognized in electron mierographs. The chief cells contain within theirc yto- a
d
e
plasm mitochondria, endoplasmic reticulum, and Golgi bodies similar to those d
found in other endocrine tissues as well as frequent PAS-positive granules. The from
juxtanuclear body of the light microscopists is identified with stacks of parallel http
lamellar elements of the endoplasmic rcticulum of the ergastoplasmic or granular ://ru
type. pre
Oxyphll cells are characterized by juxtanuclear bodies and by numerous mito- ss.o
chondria found throughout their cytoplasm. Puzzling lamellar whorls are described rg
in the cytoplasm of some oxyphil cells. /jcb
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and The contains endothelium numerous of pfeanresattrhatyironosi d capillaries as well as is extraemne ly thin extensive system in some of vesicles. areas rticle-p
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The possible significance of these structures is discussed. f/4
The connective tissue elements found in the perivascular spaces of macaque /1/1
3
parathyroid are described. /1
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6
9
7
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INTRODUCTION Other contributions to the present concepts con 0/1
3
cerning the human parathyroid can be found in the .p
some It is observatitohnes purpose ofo n the the present fine structurep aper to of report the reports of Bergstrand (7), Morgan (34), Pappen- df by g
heimer and Wilens (45), Castleman and Mallory u
psacorpae thyroid and tghlea nd techniques employing of the thin electron micro- sectioning. (10), and Gilmour (20). est on
Throughout this study an attempt is made to cor- Valuable contributions to the understanding of 09 M
parathyroid structure of other mammals are con- a
rweiltah te those fibnadsiendg s made on wiltihg ht them icroscopy. electron microscope tained in the descriptions of the parathyroids of the rch 20
In 1880 Sandstr6m (32), in a classical paper, cat by Kohn (25), the horse by Bobeau (8), the 23
described the constant presence of small epithelial rat by Rosof (51) and by De Robertis (15), the
glandular organs in or near the thyroid of man and mouse by Foster (17), the dog by Bensley (5), and
several other mammalian species. Since then many the macaque monkey by Cowdry and Scott (11)
anatomists and cytologists have studied the and by Baker (3). An extensive review of the
parathyroid glands of a variety of mammalian literature regarding parathyroid structure up to
species. Welch in 1898 (55) outlined much of the 1939 can be found in the report of Bargmann (4).
classical histology of human parathyroid as it is More recently Lever (29, 30), utilizing the elec-
generally accepted today and was the first to tron microscope, has described some aspects of the
recognize and describe accurately the oxyphil cells. fine structure of rat parathyroids.
This present paper confirms many of the obser-
* This study was supported in part by grants from
vations reported in papers mentioned above, and
the Life Insurance Medical Research Fund and from
the United States Public Health Service, Department in addition presents some new findings not yet in-
of Health, Education and Welfare (Grant H-2598.) cluded in the literature.
31
J. BIOCHEM. CYTOL., AlqV BIOPHYSIC. 1~58, Vol. 4, No. 1
14 FINE STRUCTURE OF PARATHYROID GLAND
Materials and Methods of ribonucleaso prepared from a commercial prepara-
tion 1 of crystalline salt-free ribonudease and distilled
The macaque monkey was selected as the animal of
water. The sections were flooded with the enzyme solu-
choice for this study, since the parathyroids obtained
tion and incubated at 37°C. for 3 hours. Control sections
from the mature monkey possess both chief cells and
were handled in exactly the same manner as the experi-
oxyphil cells (11, 3). The parathyroids of the more
mental sections, except that distilled water was substi-
common laboratory animals are said to contain only
tuted for the enzyme solution. Following the incubation
chief cells.
both experimental and control sections were simul-
Mature male and female monkeys of the species,
taneously stained with various dyes, including iron
Macaca mulatta, were anesthetized by intravenous
hematoxylin, gallocyanin-chromalum, and others
injection of pentobarbital sodium. The thyroid gland
known to stain intensively structures with a high con-
was exposed with a minimum of trauma and the ex-
tent of nucleic acids.
ternal parathyroids were located on the lateral aspect of
each thyroid lobe, embedded within the tissue of the
SNOITAVRESBO
thyroid just below its surface.
In most animals one external parathyroid was pre- ehT lanretxe dioryhtarap sdnalg fo eht euqacam
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pared for examination with the electron microscope yeknom era desopmoc fo a compact amyhcnerap ow
n
while the other was reserved for study by light micros- gniniatnoc owt basic cell types: chief sllec dna lo
a
copy. lihpyxo .sllec A profuse krowten fo ralucsav ded
The parathyroids used for study with the electron ,slennahc with detaicossa raluesavirep ,serutcurts fro
m
amliicrvoesc ope and were were fixed removed immediately while thien a animal 1 per cent was solu- still sesrevart eht esned stroma fo eht .dnalg http
tion of osmic acid buffered with veronal acetate to pH ://ru
hou7.3-7.5 r. (35). The duration of the fixation was ~ to 1 Chief General Cells: Features.--The chief cell is by far the press.org
Attempts were made to perfuso the parathyroids of predominant cellular element in the parathyroid of /jcb
tdthohrueeb et thyroid anaism als to theg land withsuccess darkened the of fixattihvee, immediatelyperfusions, but there since, on completion was although some cetlhl,e monkey. can be Only identified one distinct in these type, tphree parations, pale chief /article-pd
of the pedusion, rapid blackening of the external although Baker (3), it should be noted, has de- f/4/1
parathyroids was not observed. The parathyroids were scribed pale and dark chief cells in this same /13
removed immediately following the perfusion and were species. The appearance of the pale chief cell as /106
9
then handled in the same manner as described above for observed here confirms, in general, the descrip- 79
0
tissue prepared by immersion fixation only. Little dif- tion of this cell by Baker (3). Certain cytoplasmic /1
3
ference was noted in the quality of fixation between the structures can be identified in virtually each chief .pd
perused tissue and the tissue exposed only to immersion cell ~ollowing adequate preparation of the tissue. f by g
fixation. Numerous small, rod-shaped and filamentous ue
Following fi afion, the tissue was washed, dehy- mitochondria are seen which, though distributed st on
drated in alcohol, embedded in methacrylate, and 0
diffusely throughout the cytoplasm, have a 9
sectioned in the usual manner on a Servall microtome M
originally designed by Porter and Blum (49), with glass tendency to be congregated at the vascular pole of arch
knives similar to those described by Latta and Hart- the cell (Fig. 1). A distinctive, compact, relatively 20
2
mann (28). The sections were examined with an RCA large, dense, deeply basophilic structure, pre- 3
EMU 2C electron microscope equipped with a com- viously described in the parathyroids of man and
pensated objective. Either 50 or 001 ~ objective aper- the macaque monkey (45, 11, 3) and designated by
tures were used. Original magnifications of the electron Pappenheimer and Wilens as the "juxtanuclear
micrographs ranged from 1500 to 7500 diameters, as body," is present in each chief cell. Several pro-
calibrated with polystyrene latex (2, 19). Further
files of juxtanuclear body material are frequently
magnification was achieved photographically.
present in a single chief cell (Figs. 2 to 4).
The parathyroids used for study with the light
When tissue sections of macaque parathyroid are
microscope were fixed immediately after extirpation in
subjected to hydrolysis with a ribonuclease solu-
either Bouin's or Helly's solution. The glands were
sectioned at 4/~ and a variety of staining techniques tion and subsequently stained with basic stains as
were employed, including the Altmann-Kull method described above, the juxtanuclear bodies still stain
for mitochondria (9), the periodic acid Schiff technique lightly and can be identified, but the basophilia is
(23), toluidine blue, hematoxylin and eosin, and others.
In addition, mounted sections from 2 parathyroids 1 The ribonuclease enzyme preparation was obtained
were subjected to hydrolysis by a 0.15 per cent solution from General Biochemicals, Inc., Chagrin Fails, Ohio.
JERRY STEVEN TRIER 51
strikingly less intense when compared with those in length. The submicroscopic structure fo the mito-
control sections which have not been treated with chondria present in parathyroid chief cells is consistent
ribonuclease solution (compare Fig. 4 with Fig. 5). with Palade's description fo mitochondrial structure in
other mammalian tissues (36, 37).
The background basophilia of the cytoplasm is
Endoplasmic Ret~dum.--The endoplasmic reticulum
reduced only slightly following hydrolysis with
as seen in a variety of cells has been well described by
ribonuclease.
Porter (47, 48), Palade and Porter (41) and Palade ,83(
In many of the chief cells one can see discrete
39). Its presence in the chief cells of the rat parathyroid
small granules which stain brightly with the has already been noted by Lever (30). It has also been
periodic acid Schiff technique (23). These granules found to be a component fo the cytoplasm fo the chief
are scattered throughout the cytoplasm, often in cells fo the macaque (Figs. 6 to 8), where it is desopsid
close relation to the juxtanuclear bodies (Fig. 3). both diffusely and in well organized masses of oriented
They are here designated the PAS-positive lamellae resembling some fo the Nissl bodies described
granules. in nerve ceils by Palay and Palade .)24(
The dark chief cell described by Baker (3) could
not be identified in this study with either the light The distribution and size of the masses of Do
oriented lamellae as seen with the electron micro- w
or electron microscope. scope correlates well with the distribution and size nloa
Fig. 6 represents a low power electron micro- de
graph of a group of parathyroid chief cells. The of the jnxtanuclear body seen with the light micro- d fro
scope in virtually each chief cell. The masses have m
area portrayed is somewhat unusual in that no h
blood vessels are seen in the relatively large area of dfirmeeqnusieonntsl y fouof nd 1 to in 3 # close in section relation and to are the most cell ttp://ru
parenchyma represented. Chief cells tend to be p
caaopdmppejaaacrctalenycn et to arranged, of neighboring these cells each chief acell t low usuaolr ly opxoywpehr il lying is cells. much directly The as npuoc11). rletuis.o n This of They similaritthye cytoplasm may, permits however, (Figs. one b2 e to to foucnodnc lude 4, 6, ,01in thaaatnn dy ress.org/jcb/a
opnaer athyroid would anticipate chief cells from as the seen structure with of the macaque light chatrhaec terized juxtanuclear by body organized of the light stacks microscopist of parallel is rticle-pd
microscope. Structures easily identified include the lamellae of the endoplasmic reticulum. f/4/1
Within a single juxtanuclear body two to fifteen /1
cell nuclei, numerous mitochondria, endoplasmic 3
reticulum, fairly large granules of moderate of these membrane pairs may be present in profile /106
in normal or nearly normal sections. The mem- 97
density, and diffuse fine cytoplasmic granulation. 90
branes delimit flattened vesicles or cisternae. /1
In many places plasma membranes of adjacent 3
cchoiuefr se; cells this tend is discussed to pursue in a decotmapilelx later and in undulatthie ng paper. pOacrcaasliloneall flattened anastomoses vesicles joining are encounteredt he stacks iof n .pdf by g
favorable profiles. Thus this system of membranes ue
Nudd.--The chief cell nuclei show characteristic forms a true reticulum (Fig. 8). Numerous small, st o
n
elliptical profiles and contain one or more nucleoli (Figs. spherical, or rod-shaped particles 001 to 300 A in 09
6 and .)7 The nuclear matrix appears to contain many size, as described by Palade (39), are applied to the Ma
very fine densely packed granules, 051 to 052 A in diam- rch
outer surface of the individual membranes com- 2
eter, which are slightly more numerous at the periphery prising the granular reticulum. This feature permits 023
.sgiF( 6 and .)7 Favorable sections reveal a double
one to speak of these masses as belonging to the
nuclear membrane as described by Hartmann (22) for
nerve cells. One may also find nuclear pores (Fig. )7 ergastoplasmic or granular portion of the endo-
resembling those reported by Watson (54). plasmic reticulum.
Mitochondria.--The mitochondria fo the chief cell, In addition to the granular component of the
although numerous, are not evenly distributed through- endoplasmic reticulum described above, small oval
out the cytoplasm (Figs. ,6 ,7 and 11). Thus various and circular agranular profiles 500 to 2000 A in
sections fo the same cell may show a marked variation diameter (and looking like vesicles) are seen
in the number of mitochondria seen, depending upon
throughout the cytoplasm of the chief cells (Figs.
which area of the cell is represented. As mentioned
7 and 11).
previously, there is a distinct tendency toward congre-
gation of the mitochondria at the vascular pole of the igloG Bodies.--The presence fo the Golgi complex in
cell (Figs. 11 and 13). The chief cell mitochondria ap- chief cells fo the parathyroid as seen with the light
pear as rods or filaments of varying length, as originally microscope has been reported in a variety of mam-
described (3). In electron micrographs the profiles malian species ,7( ,61 ,81 ,62 27). However, Baker was
may be approximately 0.2/~ in width and up to 1 # in unable to demonstrate this structure in cells of macaque
61 FINE STRUCTURE OF PARATHYROID GLAND
parathyroid despite the utilization of specific stains Plasma Mer#branes.--When visualized through the
and techniques (3). light microscope, the plasma membrane surrounding
In recent years the appearance of Golgi bodies when the parathyroid chief cell appears as a straight, thin
viewed through the medium of the electron microscope membrane applied directly to the plasma membranes
has been well characterized (12, ,31 42, 53). Its presence of neighboring parenchymal cells, or, in the case of the
in rat parathyroid chief cells studied with the electron vascular pole of the ceU, applied directly to a thin
microscope has been reported (30). Golgi membranes basement membrane which stains prominently with the
and vesicles can be identified in virtually each macaque periodic acid Schiff technique (Fig. 3).
parathyroid chief cell adequately prepared for electron With the greater detail revealed by the electron
microscopic study. They occupy an area of up to 4/~2 in microscope, it is evident that in some areas the apposed
favorable profiles and are generally located in the plasma membranes of adjacent macaque chief cells tend
perinuclear zone of cytoplasm (Figs. ,7 8, and 10). The to pursue complex and undulating courses, with fre-
Goigi bodies of the parathyroid are similar in structure quent infoidings of the membranes, much as reported in
to those of the gall bladder epithelium, as described by rat parathyroids by Lever (30). As a result, a complex
Yamada (56) and to the "agranular reticuinm" de- interdigitation of cytoplasmic processes of adjacent
scribed in nerve cells by Palay and Palade (42). They cells is seen, reminiscent of the manner in which pieces D
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are characterized by a series of paired, parallel agranu- of an intricate jigsaw puzzle interlock (Figs. 6 and 15). w
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lar membranes intimately associated with many small In other areas apposed cell membranes pursue a more or loa
d
vesicles. No large vacuoles in close relation to the Golgl less straight uncomplicated course with only occasional ed
substance, as described in pancreatic acinar cells (53) plicatiuns and interdlgitatlons (Fig. 11). Generally one fro
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and anterior pituitary cells (16) are seen in parathyroid sees between the dense portions of the plasma mem- h
chief cells. bofr ane lesser profiles density of aboaudtj acent 001 chief to 200 calls A ina narrowwi dth. interval ttp://rup
or PAS-Pveossiictlievse are commonly Granules.--Fairly seen in the large cytoplasm granules of adjacent In other chief areas, cells are portions separated of plasma by a variable membranes but con- of ress.org
parathyroid chief cells. These granules are filled siderable distance (Fig. 7). The intercellular space /jcb
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dweinths ity homogeneous than the surroaupnpdeianrgi ng material cytoplasm of greatofe r the la ocated connective between tissue these or plasma interstitial membranes fluid may space. represent Many rticle-p
chief cells. They are ellipsoidal and measure about finger-like projections of chief cell cytoplasm enclosed df/4
0.5 to I ~ in their greatest diameter. Several of by the continuous plasma membrane extend into this /1/1
interstitial space. A similar intercellular space has been 3/1
these granules are commonly encountered in a 0
described in rat parathyroid by Lever (29, 50). 69
section of a single chief cell. They may be found in It is possible that the plications of the chief cell 790
any cytoplasmic area of the cell, but are most phsma membranes allow the individual cells to vary /13
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commonly seen in close relation to the endoplasmic their size to some degree, as may be required during df b
retieulum (Figs. 6, 7, 11, and 15). These granules different stages of activity, without undue stretching or y g
garraen ules believed described to correspond above in the to paratghrea ph PAS-positive dealing rupture The portioofn the cell of membtrahnee. plasma membrane limiting the uest on
with light microscopic observations (p. 15) surface of the chief cell that faces the capillary, pursues 09 M
(Fig. 3). Similar structures described as ellipsoidal, eclosely ssentially applied a straight to a continuous course without basement pleatings. membrane, It is arch
spherical, or U-shaped vesicles but of greater size 2
designated as the parenchymal cell basement mem- 02
have been described previously in macaque para- 3
brane. This separates the cell from the perivascuiar
thyroid by Baker (3). Whether or not these structures surrounding the blood vessels of the para-
granules represent stored secretory product of the thyroid gland. Numerous minute vesicles, from 200 to
parathyroid, perhaps in the form of colloid, is a 400 A in diameter, similar to those described in gall
matter of conjecture. The granules have not been bladder epithelium by Yamada (56), are seen in close
observed in the process of traversing the plasma relation to this portion of the plasma membrane of the
membrane of the chief cell. chief ceil (Figs. 11 and 12). In addition, tiny cave-like
indentations similar to those described along the cell
Cytoplasmic MoJrix.--The background cytoplasmic membrane of capillary endothelial cells by Palade (38)
~natrix of parathyroid chief ceils contains small, moder- and seen in gall blaxider epithelial cells by Yamada (56)
ately dense granules approximately 100 to 200 A in (who called them ealoevac )siralulleeartni are seen along
diameter. In addition larger, irregularly shaped in- this portion of the cell membrane in favorable sections.
clusions of homogeneous dense material, thought to
Oxyphil Cell:
represent accumulations of lipide, are encountered in
varying quantities in the cytoplasm of chief cells A second, less abundant basic cell type in the
(Figs. 7 and 11). macaque parathyroid parenchyma is the oxyphil
JERRY STEVEN TRIER 17
cell. Oxyphil cells as seen with the light micro- gestive of Golgi membranes are seen. Many small
scope have been described in the parathyroid of vesicles and fine, dense granules are present in the
man (10, 20, 34, 55), cow and steer (31), and cytoplasmic matrix. Dense inclusions of ralugerri
macaque monkey (3, 11). shape and size, similar in appearance to those
Baker described pale and dark oxyphil cells in described in the section dealing with chief cells and
macaque parathyroid prepared by the usual tech- presumed to be lipide inclusions, are present.
niques. The dark oxyphils were characterized by No oxyphil cells sectioned so as to show a surface
large numbers of mitochondria and the frequent presented to a capillary were observed with the
occurrence of the juxtanudear body. In the pale electron microscope, but these were seen with the
oxyphils fewer mitochondrla were observed, and light microscope (Fig. 3).
the juxtanuclear body was seen infrequently (3). In addition to the characteristic oxyphil cells
The light microscope observations made in this described above, several other large ceils of com-
study are essentially in accord with those of Baker. parable size containing different and peculiar
Fig. 1 represents a photomicrograph of a portion of cytoplasmic structures were encountered in
monkey parathyroid prepared and stained by the macaque parathyroid. The outstanding structural Do
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Altmann-Kull technique (9). An oxyphil cell con- element present in these cells is a whorl-like struc- nlo
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taining numerous mitochondria is seen in the ture composed of laminated, concentrically ar- de
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center of the field. Fig. 3 reveals a group of oxyphil ranged, agranular membrane pairs (Figs. 61 and fro
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cells. One of them displays a prominent juxta- 17), similar in appearance to a structure described h
nuclear body. It must be emphasized that the in the cytoplasm of sympathetic ganglion cells by ttp://ru
number of oxyphil cells present in the parathyroids Palay and Palade (42). It also appears similar in p
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of the macaque monkey is extremely small. Often structure to, but of different dimensions than, ss.o
none or only one oxyphil can be identified in a cross developing myelin in peripheral nerves of chick rg
section measuring four or more mm .~ embryos as reported by Geren (18). In favorable /jcb/a
Because of this infrequency, relatively few well profiles as many as nine lamellar, agranular mem- rticle
fixed oxyphil cells could be studied via the electron brane pairs can be identified disposed around a -pd
microscope. Frequently tissue areas were en- central core of variable density. This central core f/4/1
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countered in which chief cell fixation was con- varies in appearance. It may consist of homo- 3
/1
sidered good by current criteria, but the adjacent geneous material with a density similar to that of 06
9
7
oxyphil cells revealed much fragmentation and the surrounding cytoplasm; of fine, moderately 9
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distortion of cellular contents. No distinction be- dense granular material; of uniform, dense material /13
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tween dark and pale oxyphil cells could be made in resembling lipide inclusions; or of combinations of df b
tissue studied with the electron microscope. the above (Figs. 16 and 17). The individual mem- y g
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Oxyphil cells were recognized and distinguished branes comprising the lamellar structures are st o
from chief ceils by their greater size, greater cyto- about 50 A thick and the distance between mem- n 0
9
plasm to nucleus ratio, smaller, more dense nuclei, brane pairs is about 150 A. The individual mem- M
a
and distinctive cytoplasmic content. They oc- brane pairs are in turn separated from each other rch
curred singly or in groups of two or three. by larger but variably sized spaces of intervening 20
2
3
The most striking characteristic of oxyphil cells material of the density of the cytoplasmic matrix.
is the tremendous number of mitochondria present In some profiles, anastomoses between membrane
throughout the cytoplasm (Figs. 9 and 10). pairs can be seen (Figs. 61 and 17).
These cells virtually represent sacs stuffed with Structures up to 0.5/z in their smallest diameter,
mitochondria. The mitochondrla are packed so here thought to be specialized mitochondria, are
closely that in some instances they indent one seen in intimate association with some of these
another. Their fine structure is similar to that lamellar whorls. Often these whorls appear to be
described by Palade (36, 37). These mitochondria encircled partially by bodies which might be con-
differ from those of chief cells in that the former are strued as incompletely formed mitochondria. It is
of larger size (up to 0.35 # in diameter in contrast difficult to separate the anatomic limits of these
to 0.25 # for chief cell mitochondria). Filamentous mitochondria from those of the whorl-like struc-
forms are less common, while plump, rod-shaped tures (Figs. 61 and 17). To state that these ele-
forms predominate. ments function in mitochondrial formation would
In favorable profiles small accumulations of the be pure conjecture, since no concrete evidence for
granular endoplasmic reticulum and material sug- this is at hand. However, the dimensions of the
18 FINE STRUCTURE OF PARATHYROID GLAND
membrane system of mitochondria (36) and the only barrier, other than the actual pore itself, to
membrane system of these enigmatic structures free communication of the capillary lumen with the
correlate well. Further information regarding them surrounding perivascular space is the uninter-
is desirable. rupted, thin (100 to 150 A) basement membrane,
which is closely applied to the outer limits of the
Capillaries:
capillary endothelinm. The possible significance of
The macaque parathyroid is generously en- this is discussed below.
dowed with an extensive capillary network which Other portions of the capillary endothelium re-
courses through the parenchymal substance of the veal a much thicker cytoplasmic wall without
gland. The capillary wall is described by light interrupting pores. In these thick portions are
microscopists as being composed of a single layer of cytoplasmic structures such as mitochondria, endo-
endothelial ceils closely applied to a surrounding plasmic reticulum, and Golgi bodies. In addition,
continuous thin basement membrane (4), (Fig. in these thicker areas, one sees numerous fine ves-
3). In most areas this capillary wall is so thin that icles and caveolae intraceilulares, similar to those
its total thickness is considerably less than the described in capillaries of other tissues (24, 38, 50, Do
w
limit of resolution of the light microscope. 56, 57) (Figs. 11 to 14). Larger, irregularly shaped nlo
a
Electron micrographs of parathyroid capillaries vesicles or cisterns, identified as part of the endo- de
d
confirm the presence of a single cell layer of plasmic reticulum, can also be recognized (Fig. 13). fro
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endothelium dosely applied to a thin basement In some areas small, thin, finger-like projections of h
mreegimobn rane. of the The nucleus, endothelial but frcell om is theq uite nuclear thick in area, the etndhoeth elial capillary cytoplasm lumen (Fig. can 12). be seen extending into ttp://rupre
sheet-like extensions of cytoplasm, which vary The intercellular attachments of the endo- ss.o
scaomnes iderably cell, spread in thickness circumferentially, in different foramrienags of tthhee tthheyliralo id cells are similar lining in the structure capillaries to the of the" terminal para- rg/jcb/a
capillary wall. In some areas the endothelial wall is bars" as described in gall bladder epithelium (56), rticle
extremely thin, measuring only about 250 A in its kidney glomerular endothelial cells (57), and -pd
entire thickness (Figs. 11, 12, and 14). In these pulmonary endothelium (24). f/4/1
/1
thin areas, the capillary wall appears to consist Perivascular Space: 3/10
only of two cell membranes, one facing the capil- 6
9
7
lary lumen and the other facing the adjacent base- Utilizing the light microscope, AUara (1) de- 90
/1
ment membrane, separated by a small quantity of scribed the presence of two thin basement mem- 3.p
cytoplasm. These extremely thin portions of the branes delineating the space between the paren- df b
endothelium are further characterized by the chymal ceils and the capillary endothelium of y g
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presence of numerous rounded fenestrations or human parathyroid. The presence of collagen st o
pores (Figs. 11, 12, and 14). These pores are 300 to fibers and mesenchymal cellular elements including n 0
9
700 A in diameter, approximating the size of the fibroblasts, reticnlo-endothelial ceils, and mast M
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pores described in the peritubtflar capillaries of the cells within the confines of this space has been de- rch
2
rat kidney (46). They are similar in structure, but scribed (27, 32). Lever (29) studied the subendo- 0
2
3
smaller than the pores described in the endothelium thelial space of the rat parathyroid with the
of the kidney glomerulus (21, 57) and the capillaries electron microscope and described the presence of
of the neurohypophysis (43). an amorphous material applied to, but distinct
At the peripheral limit of each capillary pore, the from, the plasma membrane of both the paren-
endothelial plasma membrane facing the capillary chymal and the endothelial cells.
lumen and the plasma membrane facing the base- The present studies with the light microscope
ment membrane are seen to be in continuity with demonstrate that this space is present in the
each other (Figs. 11, 12, and 14); hence the cyto- macaque. The two basement membranes lining it
plasm of the endothelial cell is completely in- stain intensely with the periodic acid Scbiff
vested by a plasma membrane. This type of profile technique (Fig. 3). Between these basement mem-
would be difficult to explain by artefactual rupture branes is homogeneous material which stains
of the thin, delicate endothelial process; therefore faintly with the periodate Schiff method and which
there is little doubt that these pores are definitive is thought to represent connective tissue ground
structures. In areas where the pores are present, the substance. Many cells which stain metachromati-
JERRY STEVEN TRIER 19
cally with toluidine blue are thought to represent the cytoplasm of virtually all macaque parathyroid
mast cells (Fig. 2). Other cells morphologically chief cells, is characterized by intense basophilia
suggestive of fibroblasts and macrophages are (Figs. 2 to 4). This intense basophilia is greatly re-
seen within the confines of this perivascular space. duced following enzymatic hydrolysis of tissue
Electron micrographs confirm many of the above sections of parathyroid with ribonuclease (see
findings. The submicroscopic structure of the space above, Figs. 4 and 5), and this supports the view
is in essence very similar to the fine structure of an that much of the basophilia of the juxtanudear
analogous space described in the anterior pituitary body can be attributed to ribonucleic acid. It is
(50) and the thyroid gland (14). Two distinct, con- also now known that the granular component as-
centric, thin (I00 to 150 A thick), homogeneous sociated with the endoplasmic reticulum is com-
appearing, uninterrupted, moderately dense base- posed largely of ribonucleoprotein, and it has been
ment membranes are seen completely encircling the suggested that these submicroscopic cytoplasmic
perivascular space and separating it from neighbor- particles are responsible for much of the cyto-
ing tissues. One membrane is closely applied to the plasmic basophilia encountered in active tissue
antiluminal cell membrane of the capillary endo- cells (40). The amounts, distribution, and dimen- Do
w
thelial ceils, the other basement membrane is sions of the juxtanuclear bodies within parathyroid nlo
a
closely applied to the cell membrane limiting the chief cells as seen with the light microscope and de
d
vascular pole of the parathyroid parenchymal cells. aggregations of granular elements of the endo- fro
m
These basement membranes follow closely the plasmic reticulum as seen with the electron micro- h
course of the cell membranes and are separated scope are essentially identical (Figs. 2 to 4, and ttp://ru
from them by an irregular space of decreased den- 6). Baker (3), in his description of the structure of pre
sity usually 250 to 500 A in width (Figs. ,11 12, and the juxtanudear body as observed with the light ss.o
spa15). ce However, between in basement some sections, membrane portions and poafr en- the mmaicdroesc ope, up of thresatdast es "It which frequently were somewhat appeared parallel to be rg/jcb/a
chymal cell border may be as much as 1 g wide. to each other. Usually this organelle was compact rticle
The width of the space between the two base- and elongated with some lighter internal areas." -pd
ment membranes shows considerable variation, This description correlates well with the actual ob- f/4/1
/1
some of which may be due to shrinkage artifact. served structure of this portion of the endoplasmic 3/1
The content of this space is also variable. In some reticulum as seen in parathyroid chief cells with 06
9
7
sections cellular dements suggestive of fibroblasts, the electron microscope. Thus it is apparent that 90
/1
macrophages (Fig. 15), and mast cells are seen the juxtanuclcar bodies of macaque parathyroid 3
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together with collagen fibers. In other sections chief cells represent stacks of lamellar elements of df b
only connective tissue fibers and homogeneous the endoplasmic reticuhim which are readily recog- y g
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material of medium density, interpreted as being nized with the electron microscope. st o
connective tissue ground substance, are visualized. The functional cytology of the oxyphil cells of n 0
9
There is very little connective tissue material the parathyroid continues to be an enigma. The M
a
between the parenchymal ceils of the parathyroid. long standing problem of whether the oxyphil cells rch
2
These cells are generally closely applied to one have a physiologically important but as yet un- 0
2
3
another and only infrequently is an actual space recognized role to play in the function or functions
resolved between these cellular elements. There of the parathyroid gland remains unanswered. One
are, however, sections in which a sizable inter- can suspect that a cell virtually packed with
cellular space between parenchymal cells can be mitochondria might be an important functional
seen and it is uncertain if this space represents a component of the parathyroid gland, but it must be
connective tissue space containing ground sub- admitted that few other tissue components are
stance and fibrlllar connective tissue elements currently as incompletely understood as the
(Fig. 7). parathyroid oxyphil cells, and much further work is
necessary before the full significance of these cells
DISCUSSION may be appreciated.
It is known that cytoplasmic structures contain- The fine structure of capillary endothelia of
ing a high percentage of ribonudeic acid stain endocrine glands other than the parathyroid has
intensely with ordinary basic stains. The juxta- been reported. Monroe (33) described areas of dis-
nuclear body, as seen with the light microscope in continuity in the capillary endothelium of the
20 FINE STRUCTURE OF PARATHYROID GLAND
thyroid, but Dempsey and Peterson (14) reported only structures traversed by all materials exchang-
a continuous endothelial lining in thyroid capil- ing between the parenchymal cells and the blood
laries. A similar continuous, but in some areas plasma are the two thin basement membranes and
extremely thin endothelium is reported in the the perivascular space they delineate.
electron microscopic study of the anterior pituitary
by Rinehart and Farquhar (50). Palay (43) re- The author wishes to thank Dr. H. Stanley Bennett
ported the presence of small pores or fenestrations and the other members of the Department of Anatomy
about 1000 A in diameter in the endothelium of the at the University of Washington whose kind advice,
capillaries traversing the neurohypophysis. Thus encouragement, and criticism made this study .elbissop
two types of endothelia, the continuous and the
YH'IARGOILBIB
fenestrated, have been described in endocrine
glands in recent years. .1 AUara, E., Anat. Anz., 1935, 80, 401.
Since there are numerous pores in the para- .2 Backus, R. C., and Williams, R. C., J. Appl.
thyroid endothelium, it appears that the basement Physics, ,9491 ,02 .422
membrane closely applied to the antiluminal 3. Baker, B. L., Anat. Rex,, 1942, 83, .74 Do
w
border of the endothelium may well represent the 4. Bargmann, W., I-Iandbuch der mikroskopischen nlo
ultimate filter for material exchanging across the Anatomie des Menschen .W( yon ,ffrodnelli~M ed- ade
capillary barrier between the perivascular space of 5. Bennett, itor),Berlin, H. ,.S Julius J. Biophysic. Springer, and 1939, Biochem. 6, part 2, Cyfol., .731 d from
mtahteer ial parathyroid with dimensions and the capillary smaller lumen.t han the Thus dimen- any 6. Bensley, ,6591 2, .S No. H., ,4Anat. suppl., Rec., .99 ,7491 98, 361. http://ru
sions of the pores (which would include high .7 Bergstrand, H., Acta Ideal. Scan&, 1919, 52, H. 6. pre
molecular weight proteins), may cross the endo- 8. Bobeau, G., . anat. et physiol., 1919, 47, 371. ss.o
tmheelmibalr anes barrier or cytowpilatshmo ut passing by utilizing through the paassnayge - cell .01 9. Cain, Castleman, A. J., Quart. B., and . Mallory, Micr. $c., B., 1948, Am. 89, J. 229. Path., rg/jcb/a
way afforded by the pores. It must be noted that ,5391 ,11 .1 rticle
the pores present in parathyroid endothelium have .11 Covqdry, E. ,.V and Scott, C. H., Arch. Path., ,6391 -pd
roughly 100 times the cross-sectional area of the 22,1. f/4/1
.21 Dalton, A. J., and Felix, M. D., Am..1. Anat., ,3591 /1
pores of 60 to 90 A in diameter postulated by 95, 277. 3/1
0
Pappenheimer (44) to be present in the capillaries 6
.31 Dalton, A. J., and Felix, M. D., Am. J. A~at., 9
7
of the hind limb of the cat. Why a perforated ,4591 94, .171 90
/1
endothelium is present in some endocrine glands .41 Dempsey, E. W., and Peterson, R. R., Endo- 3.p
d
but appears absent in others remains an unan- crinology, 1955, ,05 46. f b
swered question. .51 De Robertis, E., Anat. Rex., 1940, ,87 473. y g
u
of An transport alternate across or perhaps the capillary coincidental barrier mechanism of para- .61 Farquhar, ogy, 1954, M. ,45 G., 516. and Rinehart, J. F., Endocrinol- est on 0
thyroid is by that of membrane vesiculation de- .71 Foster, C. L., J. Anat., ,6491 80, .171 9 M
scribed by Palade (38) and Bennett (5). Many ..8911 GeGerould, ren, B. C. B., H., Exp. J. AppI. Cell Research, Physics, 1954, ,0591 7, ,12 .855 .381 arch 2
minute vesicles and caveolae intracellulares are 0
.02 Gilmour, J. R., J. Path. and Baa., ,9391 ,84 .781 23
present in close association with the endothelial cell
.12 Hall, B. V., Roth, E., and Johnson, ,.V Anat. Re*.,
membranes, representing structural evidence that ,3591 1.5, 315, (abstract).
the vesiculation mechanism may well be at play in .22 Hartmann, J. F., J. Comp. Neural., ,3591 ,99 .102
the transport of materials across the capillary .32 Hotchkiss, R. D., Arch. Biochcm., 1948, ,61 .131
barrier of macaque parathyroid. The minute .42 Karrer, H. E., ."3 Biophysic. and Biochem. Cytol.,
vesicles and caveolae may also be seen in favorable ,6591 2, 241.
sections in association with the parenchymal cell .52 Kohn, A., Arch. mikr. Anat., 1895, ,44 .663
.62 Kolmer, W., Anat. Anz., 1917, ,05 271.
membrane limiting the vascular pole of the paren-
.72 Landau, E., Anat. An~., 1929, 6/, .18
chymal cell. Thus the mechanism of membrane
.82 Latta, H., and Hartmann, J. F., Proc. Soc. Exp.
vesiculation may also play an important role in the
Biol. and Med., 1950, ,47 436.
exchange of material between the parenchymal cell
.92 Lever, J. D., J. Biophysic. and Biochem. Cytol.,
and the perivascular space. ,6591 2, No. 4, suppl., 293.
Thus if the endothelial pores and the mechanism .03 Lever, J. D., J. Anat., 1957, 91, .37
of membrane vesiculation are both utilized, the .13 Levine, M., Anat. Rex., ,8291 39, 293.
JERRY STEVEN TRIER 12
.23 Marine, D., in Special Cytology, (E. V. Cowdry, .64 Pease, D. C., Anat. Reg., 1955, 121, 701.
editor), New York, Paul Hoeber, 1932, 2, 823. .74 Porter, K. R., J. Exp. Mat., 1953, 97, .727
.33 Monroe, B. G., Anat. Reg., 1953, 116, 345. .84 Porter, K. R., J. Histochem. and Cytochcm., ,4591
.43 Morgan, J. R., Arch. Path., 1936, ,12 .01 2, 346.
.53 Palade, .G E., Y. Exp. Meal., ,2591 95, 285.
.94 Porter, K. R., and Blum, J., Anat. Reg., 1953, 117,
.63 Palade, G. E., Anat. Rec., 1952, 114, 427.
.586
.73 Palade, G. E., J. Histochem. and Cytochem., ,3591
.05 Rinehart, J. F., and Farquhar, M. G., Anat. Reg.,
1, .881
,5591 121, .702
38. Palade, G. E., J. Appl. Physics, 1953, 24, 1424,
.15 Rosof, J. A., J. Exp. Zool., 1934, 68, .121
(abstract).
.25 Sandstr~m, I., Upsala L~karef~ren. F~rh., 1880, 15,
39. Palade, G. E., J. Biophysic. and Biochem. Cytol.,
441, English translation by .C M. Seipel, Balti-
1955, 1, 59.
more, Johns Hopkins Press, .3391
.04 Palade, G. E., J. Biophysic. and Biochem. Cytol.,
,5591 1, 567. .35 Sj~strand, F. ,.S and Hanson, V., Exp. Cdl Re-
.14 Palade, .G E., and Porter, K. R., J. Exp. Med., search, 1954, 7, 415.
1954, 100, 641. .45 Watson, M. L., Biochim. et Biophysi~a Acta, 1954,
D
42. Palay, .S L., and Palade, G. E., J. Biophys~. and ,51 475. ow
Biockem. Cytol., 1955, 1, .96 .55 Welch, D. A., J. Anat. and Physiol., 1898, 82, 292. nlo
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.34 Palay, .S L., Anat. Reg., ,5591 121, 348, (abstract). .65 Yamada, E., J. Biophysic. and Biochem. Cytol., de
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44. Pappenheimer, J. R., Phys. Rev., 1953, ,33 387. ,5591 1, 445. fro
m
45. Pappenheimer, A. M., and Wilens, .S L., Am. J. 57. Yamada, E., J. Biophysic. and Biocl.em. Cytol., h
Path., 1935, ,11 .37 ,5591 1, 551. ttp://ru
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22 FINE STRUCTURE OF PARATHYROID GLAND
EXPLANATION OF P~TXS
snoitaiverbbA Used in serugiF
A, PAS positive granules. No, Chief ceil nucleus.
B, Basement membrane. ,cO Oxyphil cell.
C, Caveolae intracellulares. P, Endothelial pore.
,oC Chief cell. Q, Finger-like endothdial cell processes.
D, Perivascular ceil. ,gR Granular component of the endoplasmic retieulum.
E, Endothelial cell. Ra, Agranular vesicles. D
o
,G Golgi substance. S, Perivascular space. wn
H, Lipide inclusions. T, Terminal bar. loa
d
I, Interstitial space between parenchymal ceils. U, Chief cell "membrane vesicles." ed
, Jaxtanuclear bodies. V, Vesicles of Palade. from
K, Whorl-like structures. W, Plasma membrane. http
L, Capillary lumen. X, Polymorphonuclear leukocyte. ://ru
M, Mitochondrion. Z, Pores in the nuclear membrane. pre
The line in the lower right comer of each illustration equals I micron unless otherwise indicated. ss.o
rg
ETALP 3 /jcb
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Fins. 1 to 5 represent photomicrographs of macaque parathyroid. rticle
FIO. .1 An oxyphil cell, containing many mitochondrla which appear bright red in the original preparation, -p
d
is seen in the center of the micrograph. Although individual mitochondria located within the chief cell cytoplasm f/4
/1
are not resolved, the accumulation of mitochondrlal substance at the vascular pole of the chief cell can be recog- /1
3
nized in the original preparation by the more intense staining (arrow) observed in this region. Altmann-Kull, /10
6
X 1400. 97
9
FIo. 2. Two dark mast cells, staining metachromatically, are present in the perivascular space. The deeply 0/1
basophilic juxtanuclear bodies () of surrounding chief cells are dearly demonstrated. Toluidine blue, × 1400. 3.p
d
FIO. 3. A typical area of parathyroid parenchyma traversed by a profuse capillary network (L). A group of f b
oxyphll ceils is seen in the upper right comer. A basophih'c juxtanuclear body is shown to advantage in one of y g
u
e
the oxyphils (J). Small, dark granules which appear deep magenta in the original preparation are seen in the st o
chief ceils in the left half of the micrograph. In the original slide, the perivascular space (S) is a light magenta n
0
hue, outlined by the dark magenta basement membranes (B) located at the vascular poles of the chief ceils and 9 M
the antiluminal wail of the capffiary endothelinm. Periodic acid Schiff, X 1400. arch
Fro. 4. A group of chief cells representing a control section handled in the same manner as the tissue illustrated 2
0
in Fig. 5, except that this preparation was incubated with distilled water rather than ribonuclease solution. Note 23
the prominent, deeply basophilic juxtanuclear bodies (arrow). Gallocyanin-chromalum, X 1400.
FIo. 5. A group of chief cells following incubation with a 0.15 per cent solution of crystalline ribonuclease at
37 ° C. for 3 hours, followed by staining. Note the pale representation of the juxtanuclear body (arrow), which,
indeed, is scarcely discernible (compare with Fig. 4). Galloeyanin-chromalum, X 1400.