Endocrine (or internally secreting) glands are also named
ductless glands, since they lack excretory ducts. Instead, the
secretory cells release their products,
hormones, into the extracellular space. From the
extracellular space, the hormones may enter the blood stream, by
which they reach their target organs. Alternatively, the hormones
may affect nearby cells (paracrine
acting hormones).
The major endocrine glands are the pituitary gland, the pineal body, the thyroid
gland, the parathyroid gland, the pancreas, the adrenal glands, the ovaries
and the testes. In some of these glands/organs (Which
ones?) the endocrine tissue constitutes only part of the parenchyma
of the organ. Small groups or individual endocrine cells are also found in
a variety of other organs (for example the GIT and the kidneys).
The pituitary gland (or hypophysis) is attached to the inferior
surface of the brain by an extension of the nervous tissue of the tuber cinereum /eminentia mediana
of the hypothalamus, the infundibulum. The infundibulum and
small amounts of non-neural secretory tissue surrounding it form
the hypophyseal stalk. The pituitary gland is located in the sella turica, the
hypophyseal fossa of the sphenoid bone. The pituitary gland
is surrounded by a thin connective tissue capsule. The loose
connective tissue between the capsule and the periosteum of the
sphenoid bone contains a dense
plexus of thin-walled veins, which surround the entire pituitary
gland.
Macroscopically, the pituitary gland can be divided into neurohypophysis,
which includes all neuroectodemal hypophyseal derivatives, and adenohypophysis,
which includes all ectodermal hypophyseal derivatives. Adenohypophyseal tissue
extending dorsally along the anterior and lateral surfaces of the hypophyseal
stalk is also called pars tuberalis of the
hypophysis. The remainder of the adenohypophysis can be divided into a pars
intermedia and a pars distalis.
It becomes a little easier to understand the
structural divisions of the pituitary gland if you understand the
pattern of the development of this gland.
Lab: Any of
the pituitary slides available are suitable to look at the
general organization of the pituitary. Try also to identify the
portal venules (read below). Several of them can usually be seen in
the pars tuberalis, where they descend towards the pars distalis of
the pituitary. Compare your observations with plate 99 (p.622) in
Ross et al.
Draw the pituitary at low magnification and
identify its divisions (those visible in the slide) and portal
venules on your drawing.
Cells and secretory products of the hypophysis:
The pars distalis of the adenohypophysis accounts for about 75%
of the hypophyseal tissue. The glandular cells are arranged in
irregular clumps or cords between a network of capillaries with
large and irregular lumina. Connective tissue, which supports the
glandular cells, is scant. Traditionally, glandular cells are
subdivided into chromophobe cells
and acidophil and basophil (chromophil)
cells. This division into three cell types is based on their
differential staining with H&E.
Cocktails of other dyes, some of which are mentioned below, also
allow a differentiation between these cell types.
All known hormones of the
adenohypophysis are proteins or glycoproteins.
The contents of the secretory vesicles are responsible for the
staining characteristics of the chromophil cells.
Acidophil cells
(or acidophils)
Acidophils are rounded cells and typically smaller than basophil
cells. Acidophils account for roughly 65% of the cells in the
adenohypophysis.
- The most frequent subtype of acidophils are the somatotrophs (which can
be stained with the dye orange G). Somatotrophs produce
growth hormone (GH or somatotropin), which e.g. stimulates liver
cells to produce polypeptide growth factors which stimulate growth
(e.g. somatomedin which stimulates
epiphyseal cartilage - overproduction of this hormone may result in
gigantism or acromegaly).
- Mammotrophs (or lactotrophs), the second group of
acidophils, secrete prolactin. Their
number increases significantly in late pregnancy and the early
months of lactation.
Basophil cells (or
basophils)
Based on their hormone products basophils are divided into three
subtypes.
- Thyrotrophs produce thyroid stimulating
hormone (TSH or
thyrotropin).
- Gonadotrophs produce follicle stimulating
hormone (FSH), which stimulates the seminiferous
epithelium in males in addition to early follicular growth in
females. Gonadotrophs also produce luteinizing
hormone (LH), which stimulates production of
testosterone by Leydig cells in males in addition to late
follicular maturation, oestrogen secretion and formation of corpus
luteum in females.
- Corticotrophs (or
adrenocorticolipotrophs) secrete adrenocorticotropic
hormone (ACTH or corticotropin) and
lipotropin (LPH, no known function in humans). Corticotropes
are the most frequent cell type in the pars intermedia. In the pars
intermedia, the precursor of ACTH and LPH undergoes further
hydrolysis into
melanocyte stimulating hormone (MSH, increased pigmentation in patients with Addison's
disease) and a number of other peptides (among them
endogenous opioids).
When stained with the PAS reaction all three types of basophils
appear reddish. Morphological criteria may
be used, aside from the secretory products, to distinguish between
the cells, but differences are so subtle that it is hopeless to try
to tell them apart in the available preparations.
Chromophobe
cells
Chromophobe cells are unstained or weakly stained cells. Most
chromophobe cells can be assigned to the different classes of
chromophils if EM and immunocytochemistry are used. They are now
thought to represent acidophil and basophilic cells in a dormant or
recently degranulated stage (degranulation
= release of most of the secretory vesicles), but may also
include stem cells of the secretory cells.
Lab: Slides PITUITARY
(SHEEP) H&E, PITUITARY (SHEEP) PAAB+PAS+OG or PITUITARY
(SHEEP) PAS+ORANGE G. The best slide to identify the different cell
types of the adenohypophysis is the PAS+Orange G
stained one. Identify acidophils, basophils and chromophobes. Survey the tissue,
and verify that the relative frequencies of the cells are different in different
parts of the adenohypophysis.
In the H&E stained sections acidophils are dark
pink and basophils look light pink/blue. Staining in the PAAB+PAS+OG section
corresponds largely to that in the other PAS+ORANGE G section but the colours
are somewhat subdued because of the additional PAAB stain.
Draw part(s) of the adenohypophysis which contains, if
possible, all three cell types at high magnifications.
The blood supply to the pituitary gland takes on an
extraordinary complex form (e.g. confer
figure 20.2 in Ross et al.; even
this picture is a slight simplification). At this stage of
the course it is important to know that the primary capillary network in the neural part of
the hypophyseal stalk drains into 20 or more portal venules, which form a secondary capillary network in the pars distalis
of the pituitary gland. The release of
hormones from the adenohypophysis is under the control of hormones
which are produced by nerve cells in the hypothalamus. For
each hormone released by the adenohypophysis there exist release-inhibitory factors and releasing-factors. These factors are also
hormones. The axons of hypothalamic nerve cells terminate within
the neural stalk and release these regulatory factors into the
extracellular space associated with the primary capillary plexus.
They are transported towards the adenohypophysis within the portal
venules and reach their target cells via the secondary capillary
plexus.
The neurohypophysis consists of
- unmyelinated nerve fibres derived from neurosecretory cells of
the supraoptic and paraventricular hypothalamic nuclei and
- pituicytes.
Usually only the oval or round nuclei of the pituicytes are
visible. Nerve fibres typically terminate close to capillaries.
Scattered, large, and bluish-violet masses in the neurohypophysis
represent dilation of nerve fibres in which the secretory vesicles,
which contain the products of the neurosecretory hypothalamic
cells, have accumulated - they are named
Herring bodies.
The neurophypophysis expands posterior to the adenohypophysis,
where it forms the posterior lobe of the pituitary.
Release-inhibiting and releasing factors are not the only
hormones secreted in the neurohypophysis.
Oxytocin (contraction of smooth muscle cell in the uterus in
late pregnancy, milk ejection reflex) and
antidiuretic
hormone (ADH or
vasopressin) are secreted in the neurohypophysis in addition
to the hormones which regulate the activity of the
adenohypophysis.
Lab: Slides PITUITARY (SHEEP) PAAB+PAS+O.G.
or PITUITARY (SHEEP) LFB. Identify nuclei of
pituicytes and Herring bodies. Herring bodies are not quite as well-defined
structures as e.g. Hassal bodies, but rather areas of darker staining in the
tissue. You may also want to take a quick look at neurones of the hypothalamus,
part of which should be visible on the slides.
Sketch the appearance of the tissue of the
neurohypophysis at high magnification and label the structures you
can identify.
The pineal body is a flattened,
cone-shaped organ attached to the roof of the third ventricle,
where it occupies a depression between the superior
colliculi.
The pineal body is surrounded by pia mater, which functions as its
capsule and which sends connective tissue septae into the pineal
body, subdividing it into lobules.
In the pineal we find two cell types:
pinealocytes (about 95% of the cells; large, light and round
nuclei) and astrocytes (glial cells;
dark, elongated nuclei).
Aside from the cells the pineal gland also contains ..... sand -
well - brain sand (or acervuli cerebri or -
just for good measure - corpora arenacea). These are
calcium-containing concretions in the pineal parenchyma, which
increase in size and number with age. These concretions are
radioopaque, and since the pineal is located in the midline of the
brain they provide a good
midline-marker. They have have no other known function.
The most prominent secretory product of the pineal body is melatonin. The cocktail of substances
released by the pinealocytes can have several functions: they may
decrease secretory activity in most other endocrine glands (in part indirectly, by way of influencing
hypothalamic neurones), and they may "delay" puberty through
antigonadotrophic effects.
Secretory activity in the pineal gland is stimulated by darkness
and inhibited by light. Via the effects of pineal hormones on the
adenohypophysis and sex hormones it is likely that the pineal body
is involved in phenomena associated with the circadian rhythm and
seasonal phenomena (e.g. seasonal
affective disorder,
SAD). The pineal body is innervated by postganglionic
sympathetic fibres derived from the superior cervical ganglion.
Lab: Slides of the pineal body are
unfortunately not yet available. There is a chance that they will
become available in the course of the semester. Until then, have a
look at your textbook/atlas instead.
The thyroid gland is situated on the lateral
sides of the lower part of the larynx and upper part of the
trachea. The two lateral lobes of the thyroid are connected by a
narrow isthmus in front of the trachea. The size is quite variable
but typically ranges around 20g (slightly larger in females than in
males).
The thyroid gland consists almost entirely of rounded cysts,
follicles, which are separated by
scant interfollicular connective tissue. The follicle is the
structural and functional building block of the thyroid gland. It
consists of a simple cuboidal epithelium (variable - depending on
the functional state) which surrounds a lumen filled with a viscous
substance, colloid. The size of the follicles is variable ranging
from about 50 µm to about 1 mm.
The colloid is the secretory product of the follicular cell
(extracellular storage!). Its main
component, thyroglobulin, consists
of triiodothyronine and tetraiodothyronine (or thyroxine).
C cells
(or parafollicular cells) are part of the follicles. There
are only few of them, and they are typically situated basally in
the epithelium, without direct contact with the follicular lumen.
They are always situated within the basement membrane, which
surrounds the entire follicle.
Arterial supply is abundant with a dense network of capillaries
between the follicles. Sympathetic fibres
(from the superior, middle and inferior cervical ganglia)
are mainly vasomotor (there is some
evidence that sympathetic input may have a stimulatory effect on
secretory activity).
Hormones of the
thyroid gland
The main secretory products of the thyroid gland are thyroxine
and triiodothyronine. TSH stimulates the endocytosis of
thyroglobulin from the follicular lumen and the subsequent release
of its components into the blood stream. TSH also stimulates their
synthesis and release into the follicular lumen.
These thyroid hormones increase
metabolic activity in almost all tissues and organs. Many of
the other effects of the hormones are secondary to an increased
oxygen consumption of the affected cells and the energy that, as a
consequence, becomes available for cellular processes (exceptions
to this rule are e.g. effects on lipid metabolism and increases in
carbohydrate absorption in the small intestine).
C cells produce the hormone
calcitonin, which decreases blood calcium concentration by
inhibiting the resorption of bone (primarily by inhibiting
osteoclast activity).
Lab: Slide THYROID
HUMAN H&E. Identify the follicles of the thyroid gland. Have a
look at the height of the epithelium and make an educated guess at the functional
activity in the thyroid (well, when it was still alive!).
Notice the capillaries in the interstices between the thyroid follicles. C
cells are very difficult to identify.
Pick a nice follicle and draw it.
The parathyroid glands are four small oval
bodies located at the posterior surface of the thyroid gland (close
to the middle and inferior ends of the lateral thyroid lobes - but
a bit variable; the inferior pair may actually be located in the
mediastinum).
These glands are small (average total weight is about 130 mg - that's 130
milligrams) but essential for
life.
Each parathyroid gland is surrounded by a thin connective tissue
capsule. Parenchymal cells are arranged in anastomosing chords
surrounded by delicate connective tissue septae. Capillaries are
abundant. A considerable number of fat cells infiltrate the gland
(beginning around puberty) and may account for about half the
weight of the parathyroid glands in adults.
Two cell types can be
distinguished in the parathyroid glands:
- Chief cells are the most
numerous type. They are rather small, a round, light and centrally
placed nucleus and a very weakly acidophilic cytoplasm. They
synthesise
parathyroid hormone (PTH or parathormone) which is of
pivotal importance for normal calcium concentrations in the fluids
and tissues of the body. The effect is mediated by a stimulation of
osteoclastic bone resorption, intestinal calcium uptake and calcium
resorption in the kidneys. If the parathyroid glands are removed
completely, calcium concentrations decrease rapidly, leading to
tetany within 2-3 days and
eventually death if left untreated.
- Oxyphilic cells are less
frequent (entirely lacking in small children; occurring first in
children six to seven years old and afterwards increasing in number
with age - funny enough they have so far
only been demonstrated in Rhesus monkey, the ox and, of course,
humans). Their cytoplasm is strongly acidophilic, the
nucleus is small and uniformly intense basophilic. They contain
large amounts of mitochondria.
There are plenty of transitional cells, i.e. cells that
morphologically represent transitions between chief cells and
oxyphilic cells.
Both the release of calcitonin by C
cells in the thyroid gland and the release of parathyroid hormone
are regulated by negative feedback from blood calcium
concentrations.
Lab: Slides PARATHYROID
HUMAN H&E or THYROID AND PARATHYROID H&E.
Your first task, which may not be that easy, is to find the parathyroid glands.
The glands are small and usually occupy only a small fraction of the tissue
on the slide. Give it a good try before you call for help. Identify chief
cells and oxyphilic cells.
Draw a part of the tissue in which both cell types are
both visible. Include if possible some of the fat cells which may occupy a
large part of the parenchyma of the parathyroid.
This slide will not
be available in the revision boxes.
Th adrenal (or suprarenal) glands consist of an outer cortex (the main part of the adrenal
glands) and an inner medulla (which accounts for about 10% of the adrenal
glands). The gland is surrounded by a thick connective
tissue capsule. Vessels and nerves reach the medulla by way of
connective tissue trabeculae which extend from the capsule towards
the medulla. Cortex and medulla are two distinct endocrine
organs(in lower vertebrates they may
actually form two entirely separate organs).
Cortex
The cortex is divided into three concentric zones which, from
the surface inwards, are termed the zona
glomerulosa (accounting for about
15% of the cortical thickness), the
zona fasciculata (about 75%)
and the zona reticularis(about 10%). Transitions are usually
gradual.
- Cells of the zona glomerulosa are organised into small rounded
groups or curved columns. Cells are smaller than in the two other
zones, their nuclei are dark and round, and the cytoplasm is light
basophilic. The zona glomerulosa is not
influenced by ACTH.
- The zona fasciculata consists of radially arranged cell cords
separated by fenestrated sinusoid capillaries. The nucleus is light
and typically located centrally. The cytoplasm is also light and
often has a characteristic foamy or spongy appearance (lipid
droplets in the cytoplasm extracted during tissue processing) -
they are for this reason also called spongiocytes.
- Anastomosing cell chords separated by sinusoid spaces form the
zona reticularis. Cells are typically smaller than in the zona
fasciculata. Their cytoplasm is eosinophilic and less spongy than
that of other cells in the cortex. The nucleus is rather light and
large. Lipofucsin, a pigment, accumulates
in the cells with age. These accumulations have an orange tinge in
H&E stained preparations.
Both the zona fasciculata and zona reticularis depend on ACTH to
sustain their function and survival.
Lab: Slide ADRENAL MKY H&E.
Try to find a transect through the adrenal gland where you can see all three
zones of the cortex and, if possible, also a bit of the medulla (see below).
Note that the relative thickness of the cortical zones may vary. It is not
always possible to identify the adrenal medulla beneath the cortex. In addition
to chromaffin cells you may find ganglion cells, sometimes in small clusters, in
the medulla. They can be recognized by the "typical" ganglion cell nucleus
- LARGE, light and with a distinct nucleolus.
Draw and label a transect of the adrenal gland which contains
the three zones and the medulla.
Hormones produced in the cortex are all steroids (consequently,
cortical cells contain large amounts of SER and lipids). Since the
hormones are synthesised in the cortex they are more precisely
termed corticosteroids.
Corticosteroids are further subdivided into mineralocorticoids (most important aldosterone; in renal tubular resorption of
sodium, excretion of potassium) and
glucocorticoids (most important
cortisol; protein catabolism in
almost all cells aside from liver cells, gluconeogenesis, glycogen
storage, mobilisation of fat from lipocytes, anti-inflammatory
effects, inhibition of allergic reactions). Small amounts of
androgens, oestrogens and progesterone are also produced.
The morphological zonation of the cortex reflects a functional
zonation in that
- mineralocorticoids are produced in the
zona glomerulosa,
- glucocorticoids are produced in the
zona fascicularis and reticularis, and
- sex hormones are produced in the zona
reticularis.
Medulla
The medulla is not sharply delimited from the cortex. Cells are
arranged in strands or small clusters with capillaries and venules
in the intervening spaces. Their cytoplasm is weakly basophilic.
They are called
chromaffin cells because the granules of these cells can be
stained with potassium bichromate. Chromaffin cells correspond to
the adrenaline- (80%) and noradrenaline-containing cells of the
medulla. The two groups cannot be
distinguished using routine histology. Chromaffin cells are
innervated by preganglionic sympathetic fibres and correspond
functionally to postganglionic neurones. The correspondence is not
only functional - chromaffin cells are,
like ganglion cells of the PNS, derived from neural crest
cells.
The adrenal medulla is not essential for life.
