Download Introduction to endocrinology 12_13

TNTRODUCTTON TO
ENDOCRTNOLOGY
E
HOMEOSTASIS
............maintains a constant internal environment.
Appropriate responses to changes in external
environment require precise coordination of the
activities of body organs and of the individual cells that
compose them.
Coordination requires exchange of information
.
.
,
between the external environment and the organism;
between the internal environment and tissue cells;
between individual tissue cells.
Thg essential information is mediated by neural and
endocrine signals.
Endocrine signals arise from
I
ClaSSical endoCrine Organs
O diffUSe endOCfing CellS
fgonads, adrenat, thyroid, pancreas........)
( in stomach, intesrine, kidney, heart........)
Routes to coordination
central:
neuroendocrine control of most classical endocrine
glands by the hypothalamus and pituitary gland.
peripheral:
more local neuroendocrine regulation of
r components of some classical endocrine glands;
, diffuse endocrine cells in the stomach, intestine,
kidney and heart.
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HORMONES
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CUBIvTICAL NATURE
Classical hormones fall into 3 categories:
{. derivatives Of tyrOsine: er*,rNES (rhyroid hormones, catecholamines)
{. derivatives of cholesterol: sTERoIDS (cortisol, oestradiol)
*
proteins and peptides: insulin, ACTH, oxytocin
AnAmnS: epinephrine, norepinephrine, T3, T4
Derived from tyrosine
Biological differences:
TuynOID HORMONES
cross cell membranes; intracellular receptors
in blood, protein-bound
stored in thyroid follicle
CeTBcnoLAMINES
do not cross membranes; cell surface receptors
in blood, free or only lightly bound
stored in membrane-bound granules
SfnnOIDS:
cortisol, oestrogen, vitamin D
derived from cholesterol
intracellul ar receptors
in blood, protein-bound
not stored in endocrine gland
PrprrnES/PROTEINS
peptides : ACTH, insulin
glycoproteins: FSH, LH, TSH
stored in membrane-bound granules
in blood, often unbound
cell membrane receptors
Endocrine
signals
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Detected only by cells that have specific receptors to which the
particular hormone will bind.
Location of receptors
Receptors may be located in the cell membrane or within the
cell, mainly in the nucleus.
Lipid-soluble steroids and thyroid hormones can pass
through the cell membrane to interact with intracellular
receptors, principally with nuclear receptors. Hormonereceptor complex activates a particular gene which is
responsible for production of a protein that causes the
hormonal effect.
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Hormones with low lipid solubility [e.g., peptide/protein
hormones and catecholamines) interact with receptors in
the cell membrane. The received signals are relayed by
second messengers that induce enzymes present already
within the cell to produce the characteristic response by the
cell.
Number of receptors
At any time, the number of receptors depends on the balance
between degradation and synthesis of receptors.
A hormone may increase the rate of synthesis of the specific
receptors in a target tissue: e.g., the increase ['up regulation')
in LH receptors induced by FSH in the granulosa cells of the
preovulatory follicle.
Alternatively, a hormone may increase the degradation
and/or decrease the synthesis of receptors in the target
organ: e.9., GnRH can 'down regulate' its own receptors in
the anterior pituitary , especially when the gonadotropes are
subjected to constant stimulation by the releasing hormone
rather than the physiological pulsatile stimulation.
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CELLS
HORMONES BINI} TO TARGET
AUT'CRINE STIMULATION:
hormone enters extracellular
spaceandbindstoreceptorsonthecellthatproducesit.
space
hormone enrers extracellular
near the producer cell'
,yprio"ated
cell
another
to
and binds
stream and
ACTIVITY: hormone enters blood
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ENDOCRINE
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THE CIASSICAI ENDOCRINE SYSTEM
NEUROENDOCRINE SYSTEM: SALIENT FEATURES
ANATOMICAL COMPONENTS
HYPOTHALAMUS
PITUITARY GLAND
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THYROID GLAND
PARATHYROID GLANDS
GONADS
PUTCENTA
MAMMARY GLI\NDS
REGULITTION OF HORMONE SECRETION
Dominant role is played by the hypothalamus, which acts as
a relay station where neural and hormonal messages are
decoded and translated into appropriate signals to ensure
the cooperation of the endocrine system with the nervous
system in regulation of the peripheral endocrine glands.
Hypothalamus contains many peptidergic neurons that
function as nerve cells and as endocrine cells. Groups of
nerve cells constitute the nuclei of the hypothalamus (e.9.,
the supraoptic and paraventricular nuclei).
The peptidergic neurons use their electrical activity to
release peptide hormones that regulate peripheral endocrine
glands--some directly, others via trophic hormones from the
anterior pituitary gland.
TYPICAL PATTERN
Hypothalamus.
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HYPOTHALAMIC. PITUITARY AXIS
ANATOMICAL COMPONENTS
Hypothalamus
Median eminence
Pituitary stalk
Pituitary gland: anterior and posterior lobes
EMBRYOLOGY OF PITUITARY GTAND
PosrenIoR L0BE : neural tissue.....downgrowth from brain......axons of peptidergic
neurons extend from hypothalamic nuclei into this lobe.....released hormones
formed in hypothalamus, not in posterior lobe ( e.g., oxytocin, vasopressinJ
ArurrnIoR LoBE: glandular tissue.... upgrowth from primitive mouth.... various
Wpes of epithelial cells, each secreting "its own" trophic hormone in response to
specific regulatory hormone delivered by the portal blood supply [e.g., thyroidstimulating hormone in response to thyrotropin-releasing hormoneJ
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Portal blood supply to anterior lobe
Primary capillary plexus.....fenestrated vessels around top of pituitary stalk
Portal venules .......running down pituitary stalk
Secondary capillary plexus..... fenestrated vessels within the anterior lobe
Secretory cells
Peptidergic neuro[S......in discrete hypothalamic nuclei-)
Epithelial cells in anterior lobe --> trophic hormones
regulatory peptides
Secretion by hypothalamic-pituitary axis
Pulsatile secretion is absolutely essential for normal hypothalamicpituitary function. Information is transferred from hypothalamus to
anterior pituitary by amplitude and frequency of pulses.
A PULSE: a discrete burst of secretion of relatively short duration and modest
amplitude.
A SUHGE occurs when a sequence of frequent pulses, often of high amplitude,
produces a massive increase extending over a period of some hours.
Cell membrane
receptors
Nuclear
recePtors
Dendrites
Uptake of
signals:..
neural
hormonal
.
Stimulatory
inPuts exceed
tfrreshold
Nucleui
Syntlresis of
regulatorY
peptide
Generate
action Potential
CellbodY
Axonal
transPort
Fenestrated caPillary
Disehai'ge of
regulatory PePtide
Storage of
regulatory
peptide
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pgpnOencrc NEURON depicts:
This diagrammatic representation of a typical
(i) the uptake of neural signals by dendrites;
iih ttr* uptake of endocrine signals by speeific receptors located either in the cell
nfembfaire (for water-soluble hormones: peptides, proteins) or in the nucleus (for
tiptC;dotuOle hormones: steroids, thyroid hormones);
(iii,,ine-eadocrine response to signals (synthesis, transport and storage of
regule{ory peptide};
(irjtr{tg *e*r^rui r""pon"" to signals (generation and conduction of action potential'
*lrict is responsible for the discharge of the regulatory peptide).
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Axons to primary
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Primary
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Portal venules
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Secondary
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Posterior pituitary
Anterior pituitary
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Gontrol of the Anterior Pituitary by Hormores
Secreted by the Hypothalamus
Hormone Secretion: Pulses and Surges
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Time
The inherent mode of secretion of hormones in the
neuroendocrine system is pulsatile and it is controlled
by an oscillator or pulse generator in the
hypothalamus.
The activity of the putse generator can be modulated
both
by neural inputs and by feedback signals from regutatory
hormones, trophic hormones and/ or hormones secreted
by peripheral endocrine cells.
FEEDBACKLOOPS
Peripheral effects of the hypothalamic-pituitary-peripheral
gland system on such key homeostatic variables as blood
concentrations of glucose, gonadal hormones or
gonadotrophic hormones are subject to self-modulation by
feedback on the activities of the hormones that regulate the
variables.
Appropriate adjustments may call for negative feedback or
positive feedback.
Some endocrine products are not regulated by feedback
(..e.,
production of androgen by the adrenal cortex is stimulated by ACTH but the androgen
does not effect the secretion of ACTH).
Three types of complex feedback loops are recognized:
. LoNc LooP: for example, gonadal hormones acting at the
level of the brain and/or pituitary gland.
.
sHoRT LooP:e.g., pituitary gonadotrophins acting at the
level of the hypothalamus.
.
uLTRA-SH0RT Loop: hypothalamic peptides acting at the
level of the hypothalamus.
The feedback effect of a particular hormone is not an
intrinsic property of the molecule itself; for instance,
although oestrogen is inhibitory (negative long loop
feedback) during most of the menstrual cycle, it exercises
an essential stimulatory effect (positive long loop feedback)
shortly before ovulation. Clearly, the message conveyed
by a hormone can vary depending on fluxes in frequency
and amplitude of its secretion.
NEGATIVE FEEDBACK
a.:.
Figure 5
.
EHDOCRINE CELL
HOHM6I.{E A
HOBMONE B
+ : STIMUI-ATI0N
.
:INHIBITION
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NEGATnIE FEEDBACK IN
OPERAIION
(a NEGATTYE FEEDBACK
ATTENUATED
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POSITIVE FEEDBACK
ENDOCRINE CELL
HOFMONEA
HOHMONE B
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POSITI\E FEEDBACK IN
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INCRE.ASED TI1OPHIC
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INCREASED POSITI1IB
FEEDBACK
:
fhe gonad,otrophias FBH and LH ftlormone lll') stimulate the secretion of oestrogen
I Herry.one B] by the graat{osa eells of the preornrlatory ovarian fotricle ( see Figure
21 )" Ee,e rryi&y ffiiffig d,Giit6ffif*tien of oestregen ( the "oestrogen s:!rger' )
stimu*ates the hypotiralam.us and ttre pittitary glaad to rBlease a srrge of
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ACTIONS of HORMONES
Stimulate ceII function
[e.9., insulin stimulates glucose uptake)
Inhibit cell function
I e.g.,somatostatin inhibits secretion of
growth hormone)
Maintain the status quo
[e.9., maintain blood calcium levels)
Stimulate or inhibit cell division
fgrowth or renewal of tissues or organs)
Stimulate cell differentiation
Stimulate or inhibit apoptosis
[programmed cell death)
Permissive role
fHormone alters sensitivity of cells to the
action of other hormones)
HORMONE ACTING PERMISSIVELY
......when presence is necessary for , or permits, a
biological response, even though the hormone does not
initiate the response.
MODE OF ACTION
I
Hormone alters sensitivity of cells to the action of
other hormones.
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May operate at level of receptors, intracellular
messengers or effector systems.
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Role often played by glucocorticoids and thyroid
hormones.
EXAMPTES
Thyroid hormone [T3J enhances the effect of epinephrine on the
mobilization of free fatty acids from adipose tissue.
In the absence of cortisol, the lipolytic effects of catecholamines
are negligible.
In the absence of cortisol, the vasoconstrictor action of norepinephrine
is compromised.
Cortisol is required for full effect of glucagon on the regulation of
glucose metabolism.
HORMONE.HORMONE INTERACTIONS
) Synergistic effects :combined effect is greater than sum
of individual effects.
F Agonistic effects: two hormones have similar effects.
F Antagonistic effects: two hormones have opposing
effects.
F Trophic effects: hormone stimulates development of
another gland and secretion of that gland's hormones.
F Permissive effects: one hormone allows another
hormone to have its full effect.
D Redundancy: crucial homeostatic variables (e.g., blood
glucose, body temperature etc) are regulated by duplicative
or overlapping controls, so that the same end result can be
produced by different hormones from different sources (e.9.,
conversion of liver glycogen to glucose by glucagon from
the pancreas and by epinephrine from the adrenal medulla).
Biological significance: fail.ure of one mechanism can be
compensatedby increased activity of another mechanism.