Download Endocrine Glands 11

ENDOCRINE SYSTEM
PHYSIOLOGY
Endocrine vs Nervous System
NERVOUS
ENDOCRINE
• Uses action potentials
along axons and chemical
neurotransmitters at
synapses
• Receptors are on postsynaptic membrane
• Uses chemical hormones
released from glands into
the blood
• Receptors are on the
plasma membranes of
target cells or intercellular
• Signals are very fast
(milliseconds)
• Signals are slower
(seconds to days)
• Response is immediate
but short-lived
• Response is delayed
but more sustained
Fig. 11.1
P. 286
Endocrine glands
are ductless
glands
Blurring the edges
Specialized neurons can secrete
chemicals into the blood rather than
synaptic cleft.
• Chemical secreted is called neurohormone.
• Hypothalamus primary secretor of
neurohormones.
Some chemicals like norepinephrine is
both a neurotransmitter and a hormone.
Characteristics of Hormones
• Hormones:
– exert their effects some distance from where
they are produced
– are active under very low (picogram to
nanogram) concentrations in the blood
– usually have a short half-life in the body several seconds to 60 mins. They are degraded
by enzymes in their target cells or in the kidney
or liver.
Characteristics of Hormones
• Hormones bring about their effects by
altering cell activity. The precise response
depends on the target cell type. Typical
cellular effects include:
– Altering plasma membrane permeability
– Stimulating protein synthesis
– Activating enzymes
– Inducing secretory activity
– Stimulating mitosis
Characteristics of Hormones
• Hormones levels depend on:
– Rate of release
– Speed of inactivation and removal from
the body
• Pharmacological levels of a hormone
may have different functions than
physiological levels of the hormone
Chemical Classes of Hormones
• Amines - Derived from tyrosine or tryptophan.
Includes: epinephrine, T4, and melatonin.
• Proteins and peptides - Made from amino acid
chains. Includes: antidiuretic hormone, growth
hormone, and insulin.
• Glycoproteins - A polypeptide chain bound to one
or more carbohydrates. Includes: folliclestimulating hormone and luteinizing hormone.
• Steroids - Lipids derived from cholesterol.
Includes: testosterone, estradiol, and cortisol.
Chemical Classes of Hormones
• Hormones can also be divided into:
– Polar:
• H20 soluble.
– Catecholamines, peptides, and glycoproteins
– Nonpolar (lipophilic):
• H20 insoluble (but lipid soluble).
– Can gain entry into target cells
– Steroid hormones and T4
– Pineal gland secretes melatonin:
• Has properties of both H20 soluble and lipophilic
hormones.
Control of Hormone Release
• Synthesis and release of most
hormones are regulated by a negative
feedback system. As hormone levels
rise, they cause target organ effects
which inhibit further hormone release.
Hormone - Target Cell Specificity
• Hormones circulate to virtually all
tissues but influence the activity of
only certain tissue cells, known as its
target cells.
Hormone - Target Cell Specificity
• Hormone-receptor interaction depends
upon three factors:
– Blood levels of the hormone
– Relative number of receptors for that
hormone on the target cell
– Affinity of the bond between the
hormone and the receptor
Hormone - Target Cell Specificity
• Receptors are dynamic structures: they
can respond to rising levels of
hormones by increasing in number (upregulation) or respond to prolonged
exposure to high hormone
concentrations by reducing the number
of receptors (down-regulation).
Mechanisms of Hormone Action
• Hormones:
– Diffuse through the cell membrane and
bind to intracellular receptors (steroid
hormones & T4) or bind to receptors on
the membrane of distant cells (aminoacid based hormones).
– Carry out their effects by direct gene
activation (steroids) or through signal
transduction systems (amino-acid based).
Lipophilic steroid and
thyroid hormones are
attached to plasma
carrier proteins.

Hormones dissociate
from carrier proteins to
pass through lipid
component of the target
plasma membrane.

Receptors for the
lipophilic hormones are
known as nuclear
hormone receptors.
Steroid receptors
function within cell to
activate gene
transcription.

Fig. 11.4
P. 292
Each nuclear hormone
receptor has 2 regions:

A ligand (hormone)binding domain.
DNA-binding domain.

Receptor must be
activated by binding to
hormone before binding
to specific region of
DNA called HRE
(hormone responsive
element).

Located adjacent to
gene that will be
transcribed.

Fig. 11.5
P. 293
Fig. 11.3
P. 289
The carrier
protein for T4 is
thyroxine-binding
globulin (TBG).
Free T4 passes
into cytoplasm and
is converted to T3.
Nonspecific
binding proteins
shuttle it to the
nucleus
Receptor proteins
are in the nucleus.

Fig. 11.6
P. 294
T3 binds to ligandbinding domain.
Other half-site is
vitamin A derivative
(9-cis-retinoic acid).

DNA-binding domain
can then bind to the
half-site of the HRE.

Two partners can
bind to the DNA to
activate HRE.

Stimulate transcription
of genes.

Fig. 11.7
P. 294
Adenylate Cyclase-cAMP
Fig. 11.8
P. 295
Polypeptide or glycoprotein hormones bind to receptor
protein causing dissociation of a subunit of G-protein.
G-protein subunit binds to and activates adenylate
cyclase. ATP
cAMP + PPi
cAMP attaches to inhibitory subunit of protein kinase.
Inhibitory subunit dissociates and protein kinase is
activated.
Phosphorylates enzymes within the cell to produce
hormone’s effects.
cAMP inactivated by phosphodiesterase, which
hydrolyzes cAMP to inactive fragments.
Phospholipase-C-Ca2+
Fig. 11.9
P. 297
Phospholipase-C-Ca2+
Ca2+ diffuses
into the
cytoplasm and
binds to
calmodulin.
Calmodulin
activates
specific protein
kinase
enzymes.

Epi Can Act Through Two 2nd
Messenger Systems
Fig. 11.10
P. 297
Tyrosine Kinase
Stimulate glycogen, fat and protein synthesis.
Stimulate insertion of GLUT-4 carrier proteins.

Fig. 11.11
P. 298
HORMONE
GLAND
NORMAL EFFECTS
OF HORMONE
CONTROL OF
RELEASE
TARGET
ORGAN
EFFECTS OF
HYPER- AND
HYPOSECRETION
Pituitary
Pituitary gland
(hypophysis) is
located in the
diencephalon.
Structurally and
functionally divided
into:

Anterior lobe =
Adenohypophysis
Posterior lobe =
Neurohypophysis

Fig. 11.12
P. 299
Pituitary
• Anterior pituitary (adenohypophysis):
– Master gland
– Derived from a pouch of epithelial tissue that
migrates upward from the mouth.
• Consists of 2 main parts:
– Pars distalis: anterior portion.
– Pars tuberalis: thin extension in contact with the
infundibulum.
• Posterior pituitary(neurohypophysis):
– Formed by downgrowth of the brain during
fetal development.
– Is in contact with the infundibulum.
Pituitary Hormones
Fig. 11.14
P. 302
Gonadotropins
• The gonadotropins are:
– Follicle-stimulating hormone (FSH) Responsible for gamete production in both sexes.
– Luteinizing Hormone (LH) - In females works
with FSH to cause follicle development, and then
independently is responsible for ovulation. In
males it is sometimes called interstitial cellstimulating hormone (ICSH), because it
stimulates the interstitial cells to produce
testosterone
THYROID-STIMULATING HORMONE
• Thyroid-stimulating Hormone
(Thyrotropin; TSH) -  chain of 96
amino acids;  chain of 112 amino
acids.
– Acts on the thyroid follicle cells to
stimulate thyroid hormone synthesis
ADRENOCORTICOTROPIC HORMONE
• Adrenocorticotropic Hormone
(ACTH) - polypeptide of 39 amino
acids
– Stimulates cells of adrenal cortex to
increase steroid synthesis and secretion
GROWTH HORMONE
• Growth Hormone (Somatotropin) protein of 191 amino acids.
– General anabolic stimulant
– Works by stimulating production of an
insulin-like growth factor (IGF-1;
somatomedin C) in the liver
– IGF-1 stimulates uptake of amino acids
and sulfur, particularly on developing
bone, and mobilizes fat from fat depots
GROWTH HORMONE
• Gigantism refers to a
condition characterized by
extreme physical size and
stature due to a
hypersecretion of growth
hormone during infancy,
childhood or adolescence
12 year-old with mother
GROWTH HORMONE
Dwarfed brothers with
researcher in India
• Dwarfism results from a
GH deficiency in
childhood, leading to a
maximum height of 4 feet
typically with normal body
proportions. If diagnosed
before puberty, hormone
replacement therapy can
promote nearly normal
growth.
PROLACTIN
• Prolactin (PRL) - Protein hormone of 199
amino acids. In females it stimulates milk
production by the mammary glands. There
is some evidence it enhances testosterone
production in males.
• Release is inhibited in non-pregnant
women. As estrogen and progesterone
levels rise late in pregnancy, it stimulates
prolactin release.
PROLACTIN
• Hyperprolactinaemia
can cause menstrual
problems in females
and breast enlargement
in males.
• Pituitary tumors is a
major cause of the
condition.
MELANOCYTE-STIMULATING HORMONE
• Melanocyte-stimulating Hormone
(MSH) - Derived from a prohormone
called pro-opiomelanocortin (POMC) - 
chain of 13 amino acids;  chain of 18
amino acids;  chain of 12 amino acids. The
major products of POMC is -endorphins,
MSH, and ACTH.
MELANOCYTE-STIMULATING HORMONE
– Stimulates pigmentation in
fishes, amphibians and reptiles
by enhancing the dispersion of
melanin from melanocytes
– In birds and mammals, blood
levels are insignificant. It will
cause darkening of the skin if
injected into the circulation,
but may be more important as a
neurotransmitter in humans
than in skin pigmentation.
NEUROHYPOPHYSIS
• Hypothalamus
neuron cell bodies
produce:
– ADH: supraoptic
nuclei.
– Oxytocin:
paraventricular
nuclei.
• Transported along
the hypothalamohypophyseal tract.
• Stored and released
from posterior
pituitary.
Fig. 11.13
P. 301
ANTIDIURETIC HORMONE
• Antidiuretic Hormone (ADH; vasopressin) oligopeptide of 9 amino acids.
– The main regulator of body fluid osmolarity
– Increases the reabsorption rate of water in
kidney tubule cells; under high
concentrations promotes vasoconstriction
– Secretion is regulated in the hypothalamus
by osmoreceptors, which sense water
concentration
OXYTOCIN
• Oxytocin - oligopeptide of 9 amino acids
• hormonal trigger for milk ejection (the
letdown reflex) in women whose breasts are
actively producing milk
• a strong stimulant of uterine contraction,
and is released in progressively greater
amounts as birth nears.
Hypothalamic Control of the
Anterior Pituitary
Hormonal control rather
than neural.
Hypothalamus neurons
synthesize releasing and
inhibiting hormones.
Hormones secreted into
the hypothalamohypophyseal portal
system regulate the
secretions of the anterior
pituitary

Fig. 11.15
P. 303
Secretions are
controlled by negative
feedback inhibition by
target gland hormones.

Negative feedback at 2
levels:

The target gland
hormone can act on the
hypothalamus and inhibit
secretion of releasing
hormones.
The target gland
hormone can act on the
anterior pituitary and
inhibit response to the
releasing hormone.

Fig. 11.17
P. 304
Adrenal Gland
• Paired organs that cap the kidneys.
• Each gland consists of an outer cortex and
inner medulla.
Adrenal Cortex
Adrenal cortex:

Does not receive
neural innervation.
Must be stimulated
hormonally (ACTH).

Consists of 3
zones:

Zona glomerulosa.
Zona fasciculata.
Zona reticularis.

Secretes
corticosteroids.

Fig. 11.18
P. 305
Corticosteroids
• Zona glomerulosa:
– Mineralcorticoids (aldosterone):
• Stimulate kidneys to reabsorb Na+ and secrete K+ by
stimulating transcription of Na+/K+ pumps..
• Zona fasciculata:
– Glucocorticoids (cortisol):
• Inhibit glucose utilization and stimulate
gluconeogenesis.
• Zona reticularis (DHEA):
– Gonadocorticoids:
• Supplemental sex hormones.
GLUCOCORTICOIDS
• At high concentrations, cortisol has
pronounced anti-inflammatory and
anti-immune effects including:
– Depressing cartilage and bone formation
– Inhibiting inflammation by stabilizing
lysosomal membranes
GLUCOCORTICOIDS
• Cushing’s disease results
from glucorticoid excess. It is
often a result of administration
of pharmacological doses of
glucocorticoid drugs.
Symptoms include persistent
hyperglycemia, loss of muscle
and bone protein, moon face,
and a redistribution of fat to
the abdomen and posterior
neck (causing a “buffalo
hump”).
GLUCOCORTICOIDS
• Addison’s disease is the major
hyposecretory disorder of the
adrenal cortex, usually involving of
both glucocorticoids and
mineralcorticoids. Victims lose
weight, demonstrate hypoglycemia
and reduced levels of sodium, and
show an increase in skin
JFK had Addison’s, which he
pigmentation (bronzing) due to
kept from public knowledge
increased ACTH levels.
GONADOCORTICOIDS
• Androgenital syndrome hypersecretion of androgens
from the adrenal cortex.
Most often apparent in
women (since the gonadal
levels of androgens often
mask the effects in men), it
manifests itself in hirsutism
and growth of the clitoris to
resemble a small penis.
Olga Roderick, the
“Bearded Lady”
Fig. 11.19
P. 306
Adrenal Medulla
Adrenal medulla:
Derived from
embryonic neural
crest ectoderm
(same tissue that
produces the
sympathetic
ganglia).
Synthesizes and
secretes:

Catecholamines
(mainly Epi but
some NE).

Adrenal Medulla
Innervated by
preganglionic
sympathetic axons.

Increase respiratory
and heart rate.
Constrict blood
vessels, thus
increasing venous
return.
Stimulate
glycogenolysis and
lipolysis.

Thyroid Gland
Thyroid gland is
located just below the
larynx.
Thyroid is the largest
of the pure endocrine
glands.
Follicular cells
secrete thyroxine.
Parafollicular cells
secrete calcitonin.

Fig. 11.21a
P. 308
Production of Thyroid Hormones
Fig. 11.23
P. 309
Iodide (I-) actively transported into the follicle and
secreted into the colloid. Oxidized to iodine (Io).
Iodine attached to tyrosine within thyroglobulin chain.
Attachment of 1 iodine produces monoiodotyrosine (MIT).
Attachment of 2 iodines produces diiodotyrosine (DIT).

MIT and DIT together produce T3
2 DIT molecules coupled together produce T4

TSH stimulates pinocytosis into the follicular cell.

Enzymes hydrolyze T3 and T4 from thyroglobulin.

Attached to TBG and released into blood.

T3
• T3 is about ten times more active than T4,
and most peripheral tissue have enzymes
that can convert T4 to T3 by removing one
iodine group. Actions of T3 include:
• Stimulates protein synthesis.
• Increases metabolic rate and heat.
– Stimulates increased consumption of glucose and fatty
acids.
• Stimulates rate of cellular respiration.
• Important regulator in tissue growth and
development.
Fig. 11.25
P. 310
A lack of negative feedback inhibition stimulates TSH,
which causes abnormal growth.
Goiter - Due to iodine
deficiency
Hypothyroid in Adults
– Adult myxedema:
• Accumulation of
mucoproteins and fluid
in subcutaneous tissue.
– Symptoms:
• Decreased metabolic rate.
• Weight gain.
• Decreased ability to adapt
to cold.
• Lethargy.
Hypothyroid in Infants
– Cretinism:
– Hypothyroid from end
of 1st trimester to 6
months postnatally.
• Severe mental
retardation
• Short disproportionately
sized body with a thick
neck and tongue
Hyperthyroid in Adults
• Grave’s disease:
– Autoimmune disorder:
• Exerts TSH-like effects on
thyroid.
• Elevated metabolic rate
(rapid heartbeat,
sweating, nervousness)
and exophthalmos
(protrusion of the
eyeballs).
HORMONES OF CALCIUM BALANCE
• Calcitonin - protein of 32
amino acids.
– Produced by thyroid
parafollicular cells
– Reduces serum calcium levels
by inhibiting osteoclast activity
and stimulating calcium uptake
in bone
– Important only in childhood
when bones are quickly growing
HORMONES OF CALCIUM BALANCE
• Parathyroid Hormone protein of 84 amino acids.
– Produced by parathyroid
glands
– Increases serum calcium
levels by stimulating
osteoclasts, enhancing
absorption of calcium in
the small intestine, and
promoting Ca2+
reabsorption in the kidney
Fig. 11.28
P. 312
Fig. 11.29
P. 312
Pancreatic Islets (of Langerhans)
Fig. 11.30
P. 313
GLUCAGON
• Alpha cells secrete glucagon - peptide
of 29 amino acids.
– Stimulus for release is decrease in blood
glucose levels
– Synthesized as a larger proglucagon molecule
and then clipped down by enzymes
– Potent hyperglycemic agent - major target
organ is the liver
– Stimulates glycogenolysis and lipolysis
INSULIN
• Beta cells secrete insulin - peptide
of 51 amino acids.
– Synthesized as a larger proinsulin molecule and
then clipped down by enzymes.
– Lowers blood glucose by enhancing membrane
transport of glucose into body cells (especially
muscle and fat cells). The brain, kidney and
liver have easy access to glucose and do not
require insulin.
– Inhibits glycogenolysis and gluconeogenesis
INSULIN
• After glucose enters a target cell,
insulin binding triggers enzymatic
activity that:
– Catalyze the oxidation of glucose for ATP
production
– Join glucose molecules together to form
glycogen
– Convert excess glucose to fat
Fig. 11.31
P. 313
INSULIN
• Diabetes mellitus results from
hyposecretion of insulin or
hypoactivity of insulin. When
insulin is absent or deficient,
blood sugar levels remain high
after a meal because glucose is
unable to enter most tissue cells.
DIABETES
• Type I diabetes mellitis (insulindependent) afflicts 750, 000 Americans.
– Autoimmune disease (beta cells are
attacked by immune cells). May be due to
a virus entering the body and mimicking
beta cell antigens.
– Insulin is not produced or secreted,
requiring regular insulin
injections.
DIABETES
• Type II diabetes mellitis (noninsulin-dependent) afflicts 7.5
million Americans.
– Insulin resistance - Insulin is usually
produced but the receptors do not respond.
– The membrane protein PC-1 may be a
culprit - it has been shown to inhibit the
tyrosine kinase receptor, but its
mechanisms of action are unknown.
DIABETES
– Heredity plays a role - an estimated 30% of
Americans carry a gene that predisposes
them to Type II diabetes.
– Lifestyle play a role - Type II diabetics are
almost always obese and sedentary. Adipose
tissue produces a hormone-like chemical
called tumor necrosis factor-alpha, which
depresses synthesis the cellular glucose
transporter (glut-4). Cells cannot take up
glucose in the absence of glut-4.
DIABETES
• Three clinical signs of diabetes:
– Hyperglycemia -normal blood sugar
should be 80 - 120 mg/dl.
– Glucosuria - glucose spills into the urine
at high blood concentrations (300 mg/dl).
– Ketoacidosis and ketouria - as sugar is
not available for fuel and lipolysis
accelerates.
PINEAL GLAND
• Secretes melatonin:
– Production stimulated
by the
suprachiasmatic
nucleus (SCN) in
hypothalamus.
• SCN is primary center
for circadian rhythms.
• Melatonin secretion
increases with darkness
and peaks in middle of
night.
– May inhibit GnRH.
– May function in the
onset of puberty
(controversial).
Fig. 11.32
P. 314
MELATONIN
The Midnight
Sun
• Melatonin secretion has been
linked to seasonal affective
disorder (SAD) in people living
in northern latitudes like Alaska.
Melatonin is elevated in the winter
months, and it may lead to
depression, long bouts of sleeping,
and eating binges. Sun lamps with
a full spectrum of light are helpful
therapy for some people.
Gonads and Placenta
• Gonads (testes and ovaries):
– Secrete sex hormones.
• Testosterone.
• Estradiol 17-b.
• Progesterone.
• Placenta:
– Secretes large amounts of estriol, progesterone,
human chorionic gonadotropin (hCG).