William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA
A GENERAL CHARACTER
l These are potent chemical substances travelling via the bloodstream from
one cell to another. They work in conjunction with the nervous system to
control the homeostasis of the body, and to anticipate future
events such as birth, lactation, fighting or fleeing. Powerpoint
2 The hormone reaches many cells but, except for hormones affecting
growth and some general metabolic processes, only certain target or
end-organ cells respond. The response is often a start or increase in a
cell's activity, e.g., contraction, release of a secretion, growth by
proliferation (hyperplasia) or by an increase in size (hypertrophy).
However, a hormone may sometimes inhibit a cell's activity, e.g.,
calcitonin inhibits osteoclasts' resorption of bone.
3 The hormone may stimulate its target cell either by binding with a
membrane receptor in the plasmalemma that starts a signal
transduction sequence, say, to alter the level of a second, internal,
messenger, within the cell, e.g., cyclic AMP or GMP; or by penetrating the
cell membrane and binding with a cytoplasmic receptor. Once inside the
cell the bound hormone itself, the second messenger, or downstream
effectors such as Ca2+, can trigger the release of secretion, an increase
in nucleus-controlled synthesis, a contraction, or some other useful task.
4 In its usual concentrations, a hormone's action is called physiological.
Pharmacological effects are seen when abnormally high quantities are
Pathological effects are observed when: too little or too much hormone
is present; the target organ is insensitive to the hormone; or the hormone
molecule is defective.
B CHEMISTRY OF HORMONES
l Hormones differ chemically and may be classified thus:
2 Hormones may be bound to proteins for storage, e.g., to
thyroglobulin in thyroid colloid; or for transport, down a
neurosecretory cell's axon, or in the blood.
- (a) Amino-acid derivatives
.. (i) iodinated, e.g., tetraiodothyronine
.. (ii) catecholamines, e.g., norepinephrine
.. (iii) melatonin
- (b) Polypeptides
.. (i) oxytocin, and vasopressin (ADH)
.. (ii) glucagon and insulin
.. (iii) neuroendocrine hormones, e.g. gastrin, motilin
.. (iv) parathormone and calcitonin
.. (v) adrenocorticotrophic hormone (ACTH)
.. (vi) melanocyte-stimulating hormone (MSH)
.. (vii) hypothalamic releasing factors and somatostatin
.. (ix) atrial natriuretic factor (ANF)
.. (x) pancreatic polypeptide (PP), and leptin
- (c) Proteins and glycoproteins
.. (i) thyrotrophic hormone (TH/TSH)
.. (ii) growth hormone (GH/STH) and prolactin (PRL/MTH)
.. (iii) gonadotrophins; follicle stimulating hormone (FSH)
luteinizing hormone (LH/ICSH); chorionic gonadotrophin (hCG)
.. (iv) renin
.. (v) erythropoietin (EPO)
.. (vi) inhibin
- (d) Steroids
.. (i) mineralocorticoids
.. (ii) glucocorticoids
.. (iii) sex hormones
.. (iv) vitamin D and its metabolites.
- (e) Various agents act rather like hormones, but are not
classified as such, e.g., kinins, prostaglandins. Some peptide hormones
have local paracrine, rather than distant, endocrine, effects.
3 The small amounts of hormone normally circulating in the blood, or
present in a tissue, can be measured by two principal methods:
- (a) Bioassay - a known volume of fluid is injected into an animal
lacking the hormone, and showing some measurable deficiency. The extent to
which the injected fluid restores the animal to a normal condition gives a
measure of its hormone content. (The method is old, but still useful.)
- (b) Radioimmunoassay - using antibody to the hormone, a
radioactive label, a method of separating immunologically bound from free
hormone, a scintillation counter for determining the concentration of
radioactive material, and previously established curves.
C CYTOLOGY OF HORMONE SECRETION
l Hormones are formed in:
.. (a) pure endocrine glands, e.g., thyroid;
.. (b) mixed exocrine and endocrine glands, e.g., pancreas and testis;
.. (c) some of the cells in organs having other functions, e.g., placenta,
kidney, GI tract.
2 The hormone is a product synthesized and released by glandular cells,
mostly epithelial, but some are modified neurons or muscle cells.
3 Cells have organelles associated with synthesis, e.g., granular or
smooth ER, Golgi complex, and may store the hormone or prohormone as
membrane-bound inclusion granules. Lysosomes may be used to
destroy excess hormone. Actin filaments are used to discharge the granules
by exocytosis. The chemical nature of the hormone is reflected in the
cytology, e.g., steroid cells store the lipid precursor, but not the hormone,
and have much smooth ER.
4 The secretory granules may stain selectively because of the chemical
nature of the hormone, e.g., glycoprotein with the PAS reaction, and have a
distinctive size, shape and density in EM.
5 The stored hormone can be demonstrated in its cell by immunostaining,
using an antibody that binds specifically with that hormone, coupled with a
visually demonstrable tag, e.g., a fluorescent compound (for LM) or a
peroxidase (for EM and LM).
Catecholamines can be seen with
fluorescence microscopy after treatment with an aldehyde. The mRNA for
the hormone or its precursor, or for enzymes necessary to its synthesis, can
be seen by using in situ hybridization.
6 The synthesis of a hormone can be followed within the cell, moving
progressively between organelles and inclusions, by sequential
radioautographic following of a radioactively labelled precursor, e.g.,
an amino acid, or 125I.
7 The stimulus for the release of hormone, and the synthesis of more hormone,
.. nervous by synaptic action, e.g., adrenal medulla;
.. another hormone, e.g., TSH for thyroid follicular cells; or
.. the blood level of a non-hormonal chemical, e.g., Ca2+
for parathyroid chief cells.
8 To facilitate the blood-endocrine cell interactions, cords and small
clusters of endocrine cells are supported by reticular fibres, close to numerous
wide capillaries (sinusoidal capillaries), lined by fenestrated but
non-phagocytic endothelial cells.
D QUESTIONS TO CHARACTERISE A HORMONE
l For each hormone - questions for the physiological state:
2 For each hormone - questions for abnormal states, pathological
- Its chemical nature?
- What cell, in what part, of which organ, forms it?
- What cell specializations are associated with its synthesis, storage and
- What are other morphological details of the cell? e.g., size.
- What controls hormone release?
- Is the pathway for the control of release simple and direct, or complex
- What are the target tissues?
- What actions does the hormone have on those tissues?
- Do some effects appear more important than others?
- Do other hormones affect the same tissue? If so, how do the hormones interact?
- Do the endocrine cells and the effects of the hormone on the target change
with time? e.g., the timescales of menstruation, gestation, childhood growth.
- Are the hormone's effects the same in the two genders? e.g., the role of
prolactin in the male?
- What pre-secretion proteolytic processsing is required to release active hormone? For example,
the corticotrophs of the anterior pituitary gland employ a serine endoprotease to release ACTH
and small amounts of beta-endorphin from a 30 kDa peptide precursor - Pro-OpioMelanoCortin (POMC).
In the intermediate lobe, extra convertase enzymes increase the output of endorphin and process
ACTH to alpha-Melanocyte Stimulating Hormone (MSH).
- What are the effects of its loss?
- Is it essential for life?
- What happens when there is an excess from a tumour, or by experiment?
- To find out the pathways and mechanisms controlling hormone release: What
are the effects on the endocrine cells of:
- (a) Removing the target tissue, when it itself forms a hormone?
- (b) Giving an excess of the material, e.g., water or glucose, whose
homeostasis is being controlled?
- (c) Removing from the animal's diet the substance, e.g., Na+,
whose homeostasis is being controlled?
- (d) Interfering with possible links in the control, e.g., by cutting the
pituitary stalk, giving an antibody to neutralize a releasing factor,
sectioning nerves, e.g., vagus, or transplanting the endocrine cells?