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The Thyroid and
Parathyroid Glands
The thyroid gland produces
thyroid hormones and calcitonin
• thyroxine (known
affectionately as T4 or
L-3,5,3',5'tetraiodothyronine)
• triiodotyronine (T3
or L-3,5,3'triiodothyronine).
The thyroid hormones
Thyroid hormones affect three fundamental physiologic
processes: cellular differentiation, growth, and
metabolism.
A large majority of the thyroid hormone secreted from
the thyroid gland is T4, but T3 is the considerably more
active hormone.
Thyroid hormones are poorly soluble in water, and more
than 99% of the T3 and T4 circulating in blood is bound
to carrier proteins. The principle carrier of thyroid
hormones is thyroxine-binding globulin, a glycoprotein
synthesized in the liver. Two other carriers of import are
transthyrein and albumin.
Tyrosines
are provided from a large glycoprotein scaffold called thyroglobulin,
which is synthesized by thyroid epithelial cells and secreted into the lumen
of the follicle - colloid is essentially a pool of thyroglobulin. A molecule of
thyroglobulin contains 134 tyrosines, although only a handful of these are
actually used to synthesize T4 and T3.
Transport of thyroid hormones by blood
• Thyroid hormones are hydrophobic
compounds and therefore they used for its
transport carrier protein
• The main transporting protein is thyroxine
binding globulin (TBG). Its affinity for T4 is 10
times higher than for T3 . The further proteins,
binding thyroid hormones, are thyroxine
binding prealbumin and albumin. More than
99% of T4 is bound on plasma proteins.
• During this period the part of T4 is deionidated
to T3 because this form is tentimes more
metabolically active. Conversion of T4 to T3 is
also observed in cytosol after transport into the
target cell
Mechanism of Action and Physiologic
Effects of Thyroid Hormones
Receptors for thyroid hormones are intracellular
DNA-binding proteins that function as hormoneresponsive transcription factors, very similar
conceptually to the receptors for the steroids
hormones.
Physiologic Effects of Thyroid Hormones
• Metabolism: Thyroid hormones stimulate diverse metabolic activities
most tissues, leading to an increase in basal metabolic rate. One
consequence of this activity is to increase body heat production,
which seems to result, at least in part, from increased oxygen
consumption and rates of ATP hydrolysis.
• Lipid metabolism: Increased thyroid hormone levels stimulate fat
mobilization, leading to increased concentrations of fatty acids,
cholesterol and triglycerides in plasma.
• Carbohydrate metabolism: Thyroid hormones stimulate almost all
aspects of carbohydrate metabolism, especially increase
gluconeogenesis and glycogenolysis to generate free glucose.
Mechanism of thyroid hormone action
• Receptors for thyroid hormones are nuclear and its affinity
is tentimes higher for T3 than T4
• The amount of nuclear receptors is very low
• Four variants of nuclear receptor were observed and
mitochondrial receptor for T3 was also described
• Free thyroid hormone receptor (TR) without bound
hormone is bound to hormone response element of DNA
(HRE) and corepressor (CoR)
• After binding T3 to receptor - CoR is liberated and
coactivators (CoA) is bound and the transcription to
mRNA begins
Increased expression of proteins
by thyroid hormones
• Glycerol 3-phosphate dehydrogenase – main
component of glycerol 3-phosphate shuttle in
mitochondria (one of transport systems for
NADH into mitochondria)
• Cytochrome c oxidase – the complex
mitochondrial enzyme in the electron transport
chain (from cytochrome c to oxygen)
• ATPases – (eg. Ca ATPase of muscle cells)
• Carbamyl phosphate synthase – enzyme of
urea cycle
• Growth hormone
Hyperthyroidism
• Graves' disease, thyrotoxicosis, toxic goiter. A
disorder of excess thyroid hormone production. It
is usually linked to an enlarged thyroid gland and
bulging eyes (exophthalmos).
Typical signs of
hyperthyroidism
• nervousness,
• a small tremor of the
hands,
• weight loss,
• fatigue,
• exophthalmoses
• sweating
• heat intolerance
• stomach and intestinal
spasms.
• overgrowth of the lymph
nodes,
• blurred or double vision,
• limited swelling,
• heart and bone disorders
• breathlessness,
• palpitations,
Hypothyroidism
in adult
• Myxedema – a clinical state resulting from a
deficiency of thyroid hormones.
• Disease process: When the supply of thyroid
hormone is inadequate, a general depression of
most cellular enzyme systems and oxidative
processes results, reducing the metabolic
activity of the cells. This in turn reduces oxygen
consumption, decreases energy production, and
lessens body heat.
Symptoms of Hypothyroidism
Coarse, dry hair
Fatigue
Dry, rough pale skin
Weakness
Hair loss
Constipation
Irritability
Depression
Abnormal menstrual
cycles
Decreased libido
Memory loss
Cold intolerance (can't tolerate the cold like
those around you)
Weight gain or increased difficulty losing weight
Muscle cramps and frequent muscle aches
Hypothyroidism in children
(Cretinism)
• a condition marked by
severe lack of thyroid
function during infancy, it is
often linked to other
hormone defects. Signs of
cretinism include dwarfism,
mental deficiency, puffy
facial features, a large
tongue, navel hernia, and
lack of muscle coordination.
Calcitonin
blood
hypercalcemia
is a hormone that functions to reduce
blood calcium levels. It is secreted in
response to hypercalcemia and has at
least two effects:
1) Suppression of renal tubular
reabsorption of calcium. In other
words, calcitonin enhances excretion
of calcium into urine.
2) Inhibition of bone resorption, which
would minimize fluxes of calcium from
bone into blood.
Effects of Parathyroid Hormone
Decreased secretion of parathyroid
hormone by the parathyroid glands,
manifested as hypocalcemia.
• Symptoms: Hypoparathyroidism is often
asymptomatic in the early stages. The most
characteristic sign is tetany with paresthesias
of the lips, tongue, fingers, and feet; other
signs are carpopedal and facial spasms,
generalized muscle aches, and fatigue.
Encephalopathy, depression, dementia, and
papilledema may also be present.
Hyperactivity of one or more of the
parathyroid glands, which is manifested as
hypercalcemia.
• Symptoms: Manifestations include bone pain,
backache, pain on weight bearing, pathologic
fractures, dilute urine and hematuria, fatigue,
clumsiness, constipation, acute abdominal
pain, mood swings, and paranoia.
Epinephrine norepiphrine dopa dopamine
The water-soluble hormones.
A class of amines called cateholamines,
derivatives of catechol.
Physiological and metabolic effects of
epinephrine
1)increases blood level of glucose:
a) by stimulation of the glycogen breakdown in muscle;
b) by inhibition of the glycogen synthesis in muscle;
c) by inhibition of the glycolysis (decrease activity of
hexokinase, phosphofructokinase, and pyruvate kinase).
2) stimulation of fatty acids mobilisation in adipose
tissue;
3) stimulation of glucagon and inhibition of insulin
secretion.
Steroid hormones
Adrenocortical hormones
(glucocoticoids,
mineralocorticoids,
and androgens)
Sex hormones
(androgens,
estrogens, and
progestins).
• These hormones are lipid-soluble so there are
necessary presence of any special transport
proteins for their transport in the blood.
Cholesterol
cyt P450
Pregnenolone
Progesterone
Cortisol
Corticosterone
Aldosteron
Testosterone
Estradiol
•
Clucocorticoids
•
1.
2.
3.
Cortisol is released into
the plasma (without
storage) with a periodicity
that is regulated by the
diurnal rhythm of ACTH
release.
Plasma transport:
The most part of cortisol is
bounded with transcortin
or corticosteroid-bilding
globulins (CBG) - alfa
globulin.
Small amount of cortisol
are bound to albumin.
A free fraction about 8% active.
Regulation of Cortisol Secretion
Functions:
•
•
•
•
•
1. Increase glucose production from amino acids.
2. Promote the activation of glycogen synthetase ( and so
way increase production of glycogen).
3. Promote lipolisis and lipigenesis in different tissue
(take fatty acids from fat stores).
4. Promote proteins metabolisms (the release of amino
acids from muscle – anabolic effects).
5. Suppress the immune system (lysis lymphocytes,
decrease number of leukocytes response).
6. Anti-inflammatory and anti-allergic effect (induce the
synthesis of lipocortin, a protein that inhibits
phospholipase A2, the rate-limiting enzyme in
prostaglandin, thromboxane, and leukotriene synthesis).
Stress and the Adrenal Gland
Figure 16.15
Addison's syndrome.
• A life-threatening disease caused by partial or
complete failure of the adrenal gland.
Symptoms: Hypoglicemia, intolerans to stress,
anorexia so weight loss, weakness, decrease blood
pressue and glomerula filtration plasma Na+, and
increase glomerula filtration K, increase
pigmentation of skin (darkening of the skin –
bronze disease), loss of hunger, stomach and
intestine problems. Other symptoms are
restlessness, depression, and sensitivity to cold.
Addison's syndrome (bronze
disease)
Addison's syndrome - bronze disease
Cushing's disease
also called
hyperadrenalism –
excess glucocorticoids
(a disorder marked by
the very high release
of ACTH or adrenal
adenomas or carcinomas).
Cushing's disease
• The symptoms are
hyperglycemia, fat pads on
the chest, upper back
obesity (“buffalo hump”);
water buildup hypernatremia,
hypokalemia, alkalosis,
edema, hypertension, round
"moon" face, osteoporosis;
muscle weakness; purplish
streaks on the skin;
infection; fragile bones;
acne; and heavy growth of
hair on the face.
Mineralocorticoids
Aldosterone
1. acts on the kidney
promoting the
reabsorption of sodium
ions (Na+) into the blood.
Water follows the salt and
this helps maintain
normal blood pressure.
2. acts on sweat glands to
reduce the loss of sodium
in perspiration.
• Plasma transport: weak
association with albumin
so it very rapidly cleared
from the plasma by liver
and kidney.
The secretion of aldosterone is
stimulated by:
• a drop in the level of
sodium ions in the
blood;
• a rise in the level of
potassium ions in the
blood;
• angiotensin II
• ACTH (as is that of
cortisol)
Blood Osmolarity
ADH
increased
water
reabsorption
pituitary
increase
thirst
nephron
high
blood osmolarity
blood pressure
adrenal
gland
low
increased
water & salt
reabsorption
JuxtaGlomerular
Apparatus (JGA)
nephron
renin
aldosterone
angiotensinogen
angiotensin
Disorders of mineralocorticoid
excess:
• 1. Primary aldosteronism (Conn’s syndrome)
are resulted small adenomas of the glomerulosa
cell. Hypertension, hypokalemia, hypernatremia,
and alkalosis (plasma rennin and angiotensin II
levels are suppressed).
• 2. Secondary aldosteronism is results of renal
artery stenosis, with the attendant decrease in
perfusion pressue, what can lead to hyperplasia
and hyperfunction of the jucstaglomerylolar cell
and cause elevated level of rennin and
angiotensin II. Clinics are the same.
Adrenal hormones
dehydroepiandrosterone
•
androstendione
Play impotent role in glucose homeostasis,
sodium retention, and blood pressure regulation.,
host defense mechanisms, stress response and
general protein anabolism, and a special role
when absence hormones synthesize in adrenal
gland.
Testosterone is important for:
1. Controls development of male genitals before
birth.
2. When levels increase at puberty, secondary
sexual characteristics develop deepening voice,
muscular development, facial hair etc.
3. In adulthood it determines sexual drive, sperm
production and fertility. It is also important in
maintaining facial and pubic hair, and keeping
muscles and bones healthy. It may also be
important in protecting the heart.
Testosterone Deficiency
(hypogonadism)
• Depending on age, insufficient
testosterone production can lead to
abnormalities in muscle and bone
development, underdeveloped
genitalia, and diminished virility.
• Primary, disruption in the testicles
• Secondary, disruption in the
pituitary
• Tertiary, disruption in the
hypothalamus
Testicular
feminization
• Is a normal level of
testosterone but
defective receptors,
(XY genotype but
phenotype as
female).
Progesterone
• In luteal phase, it promote development of secretory
endometrium in preparation for implantation of the
fertilized egg.
• Control movement of the egg within lumen of fallopian tube
• During labour, it regulate uterine contraction indirectly by
inhibiting oxytocin release from posterior pituitary.
• Responsible for the increase in basal body temperature of 11.5◦F that begin shortly after the time of ovulation and
persist throughout the luteal phase of the menstrual cycle.
• Compete with aldosterone in renal tubule which lead to
modest loss of sodium and water into urine.
• Hypnotic act on the brain contribute to emotional and
physical changes sometimes seen during the immediate
premenstrual interval (PMS)
Estrogen
• Breast development and
maintenance
• Improving bone strength and
density
• Accelerating bone maturation
and bringing epiphyses to
closure, completing growth
• Growth of the uterus
• Promoting and maintaining
vaginal mucosal thickness and
secretions
• Effect on lipids
• Vascular effects
• Cerebral effects
• Development of the
endometrial lining to a
thickness necessary to support
pregnancy and menstruation
• Thinning of cervical mucus at
ovulation
• Serving as the primary
feedback to the brain of sex
hormone levels in both males
and females.
• Participating in triggering
ovulation
• Preservation of egg cells
• Enabling spermatogenesis
Brain
Heart
and
Liver
Ovary
Vagina
Breast
Uterus
Bone
Deficiency of estrogen
•
•
•
•
osteoporosis,
hypercholesterolemia,
vaginal and dermal atrophy, and
cognitive impairment
Mechanism of steroid and
thyroid hormones action
Regulation of gene expression by steroid hormones is mediated by
specific intracellular receptors. Steroid receptors (SR) belong to a
large family of ligand-inducible transcription factors.
Coactivators (such as SRC-1, CBP, p/CAF and TIF2) are
important for steroid receptors to achieve full transcriptional gene
activation. In addition, interaction with components of the general
transcription machinery -including TFIIB (IIB), TFIID complex
(IID) and members of the RNA polimerase (pol-II) complex- may
provide the mechanism by which steroid receptors achieve the
specificity required for the expression of different gene networks
in target tissues.
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