BS2050 Essential Human
Physiology in Health and Disease
Dr D R Davies
Lecture 1
Principles of Endocrinology
Hormones
• a specific chemical substance produced in
specialized endocrine cells and is released
into the bloodstream where it can exert its
effects on different cell types in other tissues
• . These are referred to as Target Cells and are
characterized by the presence of a specific
hormone receptor which is involved in the
transduction of the hormonal signal.
Endocrine Gland
• collection of specific cells (endocrine cells)
organised into a tissue whose major function
is to produce hormones in response to a
particular physiological signal or signals.
• hormones may be stored in the endocrine
gland in secretory granules as is the case with
catecholamine, peptide and polypeptide
hormones or synthesised on demand as is the
case for steroid and thyroid hormones.
Hormones exhibit a diversity of
chemical structure and size
• ranging from the glycoprotein hormones (LH, FSH,
hCG, TSH),
• larger polypeptides (insulin, ACTH, Gastrin, CRH),
• smaller modified peptides (TRH, GnRH)
• lipophilic steroid hormones (testosterone,
oestradiol, cortisol , aldosterone),
• hormones derived from amino acids (adrenaline and
thyroxine)
• or derived from fatty acids like prostaglandins.
Hormones
• produced and secreted in small quantities
(ng – mg range per day) and the blood
plasma concentration is low (1 pM – 10nM
depending on the hormone) but changes
may be 10 –100 fold in response to a
physiological signal.
• The physiological or metabolic response to
a hormonal signal is greatly amplified
compared to the change in hormone
concentration.
Hormones
• Hormones are subject to rapid turnover, so
that hormone levels rapidly rise in response
to a physiological signal and as soon as the
need for the signal disappears, the hormone
is rapidly removed from the system. The
physiological effects of the hormone may
not appear until well after the hormone
levels have returned to their original level.
Plasma Hormone Levels
• The concentration of hormone in the
blood is normally determined by its rate of
secretion by the endocrine gland. The rate
of degradation or modification of a
hormone, and thus its inactivation, is
usually a fairly constant process and can
occur in different sites within the body (e.g.
liver and kidney).
The effect of a hormone on a target
cell is dependent on two factors: (1)
 capacity of the tissue to respond to the hormone
which, in turn, is dependent on the presence of a high
affinity receptor, which binds hormone at low
concentrations of the ligand (hormone).
 receptors may be associated with the outside of the
plasma membrane (e.g. peptide, polypeptide and
catecholamine receptors) or in the cell cytoplasm or
nuclei, e.g. steroid and thyroid hormones).
The effect of a hormone on a target
cell is dependent on two factors: (2)
• concentration of hormone in the blood which,
can change about 10 –100 fold.
• This change is normally induced over a small
range of concentrations on either side of the
dissociation constant (Kd) for the hormonereceptor interaction
• depends on the rate of secretion of hormone
Sigmoidal relationship between hormone
concentration and Biological Effect
• At low concentrations the hormone level can change
without much effect, until it reaches a threshold
concentration where the magnitude of the physiological
effect is directly proportional to the hormone
concentration. At higher concentrations this proportionality
disappears and the physiological effect reaches a
maximum. An useful measurement is the concentration of
hormone at which half of the maximal physiological effect
is found. (estimated by plotting the magnitude of the
physiological response against the Log10[Hormone]).
• usually closely related to the Kd of the hormone-receptor
interaction.
Hormones regulate one or more
existing functions of target cells
 Metabolism via alterations in enzyme activities
(positive or negative effects)
 Alter Membrane permeability to specific ions
and metabolites
 Gene transcription of specific gene products, in
turn regulating cell-specific protein synthesis
 can induce secretory activity of cell
• can cause mitotic cell division
The functions of hormones are
many and varied e.g..
 The maintenance of homeostasis i.e. the
maintenance of the composition of the tissues and
body fluids for the benefit of the organism as a
whole (e.g. insulin and glucagon regulate blood
glucose within strict limits by integrated effects on
glucose metabolism various tissues).
 Hormones allow an appropriate response to
external stimuli (e.g. the effect of adrenaline in
the fight or fright response).
The functions of hormones are
many and varied e.g..
 Some hormones control cyclic and developmental
changes (e.g. they regulate the growth of the individual,
circadian rhythms or sexual function such as the
menstrual cycle, pregnancy, spermatogenesis etc)
 Hormones can cause changes in brain function and
behaviour
 Hormones often have synergistic effects – on their own
they are inactive or poorly active but, at the same
concentration, in combination with one or more other
hormones, they produce a full physiological effects.
Some hormones bind to plasma membrane receptors
and generate second messengers e.g cAMP
Others work via Inositol Phosphate and Ca2+ as
second messengers
Steroid and thyroid hormones enter cells and interact
with nuclear receptors and regulate gene expression
Major Endocrine
Glands
• Hypothalamus, and
pituitary
• Thyroid, parathyroid
• Adrenal glands - cortex
and medulla
• Pancreas - islets of
Langerhans
• Gonads – testes and
ovaries
Pituitary gland (hypophysis)
• two-lobed organ that secretes nine major
hormones
• Neurohypophysis – posterior lobe (neural tissue)
Hormones synthesised in cell body in hypothalamus
hormones, stored and released at nerve endings in the
posterior pituitary
• Adenohypophysis – anterior lobe (glandular
tissue) Synthesizes and secretes a number of hormones
in response to hormonal signals from the hypothalamus
Pituitary gland (Hypophysis)
Anterior pituitary (adenohypohysis)
• anterior pituitary arises from oral mucosa in
embryological development
• no direct neural contact with the hypothalamus
• vascular connection, the hypophyseal portal
system, consisting of:
– The primary capillary plexus
– The hypophyseal portal veins
– The secondary capillary plexus
Hormonal Stimuli
• Hormonal stimuli – release
of hormones in response to
hormones produced by
other endocrine organs
– The hypothalamic hormones
stimulate the anterior
pituitary
– In turn, pituitary hormones
stimulate targets to secrete
still more hormones
Figure 16.4
Neural Stimuli
• Neural stimuli – nerve
fibers stimulate hormone
release
– Preganglionic sympathetic
nervous system (SNS) fibers
stimulate the adrenal medulla
to secrete catecholamines adrenaline and noradrenaline
Figure 16.4
Humoral Stimuli
• Humoral stimuli – secretion
of hormones in direct
response to changing blood
levels of ions and nutrients
• Example: concentration of
calcium ions in the blood
– Declining blood Ca2+
concentration stimulates the
parathyroid glands to secrete
PTH (parathyroid hormone)
– PTH causes Ca2+
concentrations to rise and the
stimulus is removed
Figure 16.4
Hormones secreted by the Anterior
Pituitary
•
•
•
•
•
•
Adrenocorticotrophic hormone (ACTH)
Thyroid Stimulating Hormone (TSH)
Luteinizing Hormone (LH)
Follicle Stimulating Hormone (FSH)
Growth Hormone (GH)
Prolactin
Effect of
hypothalamic
releasing
hormones
TRH
CRH
GnRH
TSH
ACTH
FSH
LH