Transcript Thyroid Hormone - Collin College Faculty Website Directory

PowerPoint® Lecture Slides
prepared by
Janice Meeking,
Mount Royal College
CHAPTER
16
The Endocrine
System:
Part B
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The Anatomy and Orientation of the Pituitary Gland
Figure 18.6a, b
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Major Endocrine Organs: Pituitary (Hypophysis)
• Pituitary gland – two-lobed organ that secretes nine
major hormones
• Neurohypophysis – posterior lobe (neural tissue) and
the infundibulum
• Receives, stores, and releases hormones from the
hypothalamus
• Adenohypophysis – anterior lobe, made up of glandular
tissue
• Synthesizes and secretes a number of hormones
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Pituitary-Hypothalamic Relationships: Posterior Lobe
• Is a down growth of hypothalamic neural tissue
• Has a neural connection with
(hypothalamic-hypophyseal tract)
the
hypothalamus
• Nuclei of the hypothalamus synthesize oxytocin and
antidiuretic hormone (ADH)
• These hormones are transported to the posterior pituitary
• Stores antidiuretic hormone (ADH) and oxytocin
• ADH and oxytocin are released in response to nerve
impulses
• Both use PIP-calcium second-messenger mechanism at
their targets
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http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookENDOCR.html#Mechanisms%20of%20Hormone%20Action
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Neurohypophysis hormones
Hormones that are produced in the hypothalamus and
stored in the neurohypophysis
Hormone
Target
Effect
Antidiuretic hormone
(ADH)
Kidneys
Reabsorption of water,
elevation of blood volume and pressure
(vasoconstriction)
Arginine vasopresin
(AVP)
Oxytocin (OT)
Uterus, mammary glands
(female)
Ductus deferens and prostate
gland (male)
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Labor contractions, milk ejection
Contractions of ductus deferens and
prostate gland
Oxytocin
• Stimulates uterine contractions during childbirth
by mobilizing Ca2+ through a PIP2-Ca2+ secondmessenger system
• Also triggers milk ejection in women producing
milk
• Plays a role in sexual arousal and orgasm in males
and females
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Antidiuretic Hormone (ADH)
• Hypothalamic osmoreceptors respond to changes in
the solute concentration of the blood
• If solute concentration is high
• Osmoreceptors depolarize and transmit impulses to
hypothalamic neurons
• ADH is synthesized and released, inhibiting urine
formation
• We will talk about this hormone in details with the
urinary system
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The anterior lobe
• Is an outpocketing of the oral mucosa from epithelial tissue
• There is no direct neural contact with the hypothalamus
• Hormone production is regulated by the hypothalamus
• Regulatory factors from the hypothalamus arrive directly to the
adenohypophysis through the hypophyseal portal system
• Subdivided into the
• pars distalis – the largest and most anterior portion
• pars intermedia – a narrow band between the pars distalis and
the posterior lobe
• pars tuberalis – wraps around the proximal portion of the
infundibulum
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Hypophyseal portal system
• Portal system - a system of blood vessels that
begins and ends in capillaries. The blood, after
passing through one capillary bed, is passing
through a second capillary network.
• All blood entering the portal system will reach the
target cells before returning to the general
circulation
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Pituitary-Hypothalamic Relationships: anterior Lobe
• The hypophyseal portal system,
consisting of:
• The primary capillary
plexus in the infundibulum
• The hypophyseal portal
veins
• The secondary capillary
plexus
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Activity of the Adenohypophysis
• The hypothalamus sends a chemical stimulus to
the anterior pituitary
• Releasing hormones stimulate the synthesis and
release of hormones
• Inhibiting hormones shut off the synthesis and
release of hormones
• The hormones of the anterior pituitary (7) are
called tropic/trophic hormones because they “turn
on” other glands or organs
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Anterior Pituitary Hormones
• All are proteins
• All except GH activate cyclic AMP secondmessenger systems at their targets
• TSH, ACTH, FSH, and LH are all tropic hormones
(regulate the secretory action of other endocrine
glands)
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Anterior pituitary hormones
Region
Hormone
Target
Effect
Hypothalamic regulatory
hormone
Folliclestimulating
hormone
(FSH)
Follicle cells of
the ovaries,
sustentacular
cells of testes
Secretion of
estrogen, follicle
development,
stimulation of
sperm maturation
Gonadotropin-releasing hormone
(GnRH)
LuteinizingHormone
(LH)
Follicle cells of
ovary
Ovulation,
formation of
corpus luteum,
secretion of
progesterone
Gonadotropin-releasing hormone
(GnRH)
Interstitial cell of
testes
Secretion of
testosterone
Prolactin
(PRL)
Mammary glands Production of milk
Growth
hormone
(GH)
All cells
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Prolactin-releasing factor (PRF)
Prolactin-Inhibiting hormone (PIH)
Growth, protein
synthesis, lipid
mobilization and
catabolism
Growth-hormone- releasing
hormone (GH-RH)
Growth-hormone-inhibiting
hormone (GH-IH)
Gonadotropins
• Follicle-stimulating
hormone (LH)
hormone (FSH) and luteinizing
• Secreted by gonadotrophs of the anterior pituitary
• FSH stimulates gamete (egg or sperm) production
• LH promotes production of gonadal hormones
• Absent from the blood in prepubertal boys and girls
• Regulation of gonadotropin release
• Triggered by the gonadotropin-releasing hormone
(GnRH) during and after puberty
• Suppressed by gonadal hormones (feedback)
• We will discuss these hormones later with the reproductive
system
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Prolactin (PRL)
• Secreted by lactotrophs of the anterior pituitary
• Stimulates milk production
• Regulation of PRL release
• Primarily controlled
hormone (PIH)
by
prolactin-inhibiting
• Blood levels rise toward the end of pregnancy
• Suckling stimulates PRH release and promotes
continued milk production
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Growth Hormone (GH) or somatotropin
• GH is an anabolic (tissue-building) hormone
• Stimulate most body cells to increase in size and
divide by increasing protein synthesis
• Major target tissues are bone, cartilage and skeletal
muscle
• GH release is regulated by
• Growth hormone–releasing hormone (GHRH)
• Growth hormone–inhibiting hormone (GHIH)
(somatostatin
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Growth Hormone (GH) or somatotropin
• The stimulation of growth by GH involves 2
mechanisms:
• The primary one is indirect and more understood:
• GH influence the liver, skeletal muscle, bone, and
cartilage to release insulin-like growth factors
(IGF)/somatomedins
• The IGF binds to specific receptors on cells and
increase the uptake of amino acids and their
incorporation into new proteins
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Growth Hormone (GH) or somatotropin
• Direct effects
• In ET and CT stimulate cell division and
differentiation (the subsequent cell growth is
mediated by IGF)
• In adipose tissue GH stimulates the breakdown of
stored triglycerides by adipocytes and the release
of fatty acids to the blood. That promotes the use
of fatty acid for energy instead of the use of
glucose (glucose-sparing effect)
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Anterior pituitary hormones
Region
Hormone
Target
Effect
Hypothalamic
regulatory
hormone
Thyroid-stimulating
hormone (TSH/
thyrotropin)
Thyroid gland
Secretion of
thyroid
hormones (T3,
T4)
Thyrotropin-releasing
hormone (TRH)
Adrenocorticotropic
hormone (ACTH)
Adrenal cortex
(zona
fasciculate)
Secretion of
Corticotrophin-releasing
glucocorticoids
hormone (CRH)
(cortisole,
corticosterone)
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Thyroid-Stimulating Hormone (Thyrotropin)
• Produced by thyrotrophs of the anterior pituitary
• Stimulates the normal development and secretory
activity of the thyroid
• Regulation of TSH release
• Stimulated
(TRH)
by
thyrotropin-releasing
hormone
• Inhibited by rising blood levels of thyroid
hormones that act on the pituitary and
hypothalamus
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Adrenocorticotropic Hormone (Corticotropin)
• Secreted by corticotrophs of the anterior pituitary
• Stimulates the adrenal cortex to release
corticosteroids
• Regulation of ACTH release
• Triggered by hypothalamic corticotropin-releasing
hormone (CRH) in a daily rhythm
• Internal and external factors such as fever,
hypoglycemia, and stressors can alter the release of
CRH
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Thyroid Gland
The thyroid gland on the anterior side of the
neck. The thyroid gland has a right lobe and
a left lobe connected by a narrow isthmus
http://webanatomy.net/histology/endocrine_histology.htm
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Thyroid gland histology
• The thyroid gland contains thyroid follicles lined
with simple cuboidal epithelium – follicular cells
• The follicle cells surround a follicular cavity that
contain the colloid; a fluid that contains a large
amount of proteins - thyroglobulin that contain the
amino acid tyrosine
• Each follicle is surrounded by a capillary network.
• Between the follicles C cells/parafollicular cells
can be found
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Thyroid Hormone
• Thyroid hormone – major metabolic hormone
• Consists of
compounds
two
related
iodine-containing
• T4 – thyroxine; has two tyrosine molecules plus
four bound iodine atoms
• T3 – triiodothyronine; has two tyrosines with three
bound iodine atoms
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Synthesis of Thyroid Hormone
• Thyroglobulin is synthesized by the follicular cells
and released into the lumen
• Iodides (I–) are actively taken into the cell by
membrane carrier proteins
• The iodide ions diffuse to the apical surface of the
cells (these cells are facing towards…?), oxidized to
iodine (I2) by the enzyme thyroid peroxidase and
released to the colloid.
• Iodine attaches to tyrosine in the thyrogobulin,
forming T1 (monoiodotyrosine, or MIT), and T2
(diiodotyrosine, or DIT)
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Synthesis of Thyroid Hormone
• Iodinated tyrosines link together to form T3 and T4
• Coupling reaction
MIT + DIT  T3 / triiodothyronine
DIT + DIT  T4 / thyroxin (tetraiodothyronine)
• The colloid is then endocytosed and combined with a
lysosome, where T3 (10%) and T4 (90%) are cleaved
and diffuse into the bloodstream
• 75% of the T4 and 70% of the T3 are transported
attached to thyroid-binding protein (TBGs) and the
rest to a special albumin
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Thyroid Hormone and target cells
• Thyroid hormones influence almost every cell of the body
• Inside the cells they bind to receptors in one of 3 locations:
• In the cytoplasm – storage of thyroid hormones to be
released if the intracellular levels decrease
• On the mitochondria surface – increase rate of ATP
production
• In the nucleus – activate genes that control the
synthesis of enzymes that involve with energy
production and utilization (for example increase of
production of sodium-potassim ATPase that uses ATP)
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Other effects of Thyroid Hormone
• TH is concerned with:
• Activate genes that code for enzymes that are
involved in glycolysis (Glucose oxidation)
• Increasing metabolic rate of the cells
• Increase heat production (calorigenic effect)
• Although the major thyroid hormone that is being
produced is the T4 (90%) T3 is the one responsible
for the TH effects
• Enzymes in the kidneys, liver and other tissues
convert T4 to T3
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Transport and Regulation of TH
• Negative feedback regulation of TH release
• Rising TH levels provide negative feedback
inhibition on release of TSH
• Hypothalamic thyrotropin-releasing hormone
(TRH) can overcome the negative feedback during
pregnancy or exposure to cold
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Calcitonin
• A peptide hormone produced by the parafollicular,
or C cells
• Lowers blood calcium levels
• Antagonist to parathyroid hormone (PTH)
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Calcitonin
• Calcitonin targets the skeleton, where it:
• Inhibits osteoclast activity (and thus bone
resorption) and release of calcium from the bone
matrix
• Stimulates calcium uptake and incorporation into
the bone matrix
• Regulated by a humoral (calcium ion
concentration in the blood) negative feedback
mechanism
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Parathyroid Glands
• Four to eight tiny glands embedded in the posterior
aspect of the thyroid
• Contain oxyphil cells (function unknown) and chief
cells that secrete parathyroid hormone (PTH) or
parathormone
• PTH—most important hormone in Ca2+ homeostasis
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Effects of Parathyroid Hormone
• PTH release increases Ca2+ in the blood as it:
• Stimulates osteoclasts to digest bone matrix
• Enhances the reabsorption of Ca2+ and the
secretion of phosphate by the kidneys
• Increases absorption of Ca2+ by intestinal mucosal
• Rising Ca2+ in the blood inhibits PTH release
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Adrenal (Suprarenal) Glands
• Adrenal glands – paired, pyramid-shaped organs
atop the kidneys
• Structurally and functionally, they are two glands
in one
• Adrenal medulla – neural tissue; part of the
sympathetic nervous system
• Adrenal cortex - three layers of glandular tissue
that synthesize and secrete corticosteroids
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http://www.histology-world.com/photomicrographs/adrenallabel.jpg
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Adrenal Cortex
• Synthesizes and releases steroid hormones called
corticosteroids
• Different corticosteroids are produced in each of the three
layers
• Zona glomerulosa – glumerulus- little ball. Secretes
mineralocorticoids – main one aldosterone
• Zona fasciculata – glucocorticoids (chiefly cortisol)
• Zona reticularis – gonadocorticoids (chiefly androgens)
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Zona glumerulosa - Mineralocorticoids
• Aldosterone secretion is stimulated by:
• Rising blood levels of K+
• Low blood Na+
• Decreasing blood volume or pressure
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Zona glumerulosa - Mineralocorticoids
• The mineralocorticoids are steroids that affect the electrolytes
composition of the body extracellular fluids.
• Aldosterone – most important mineralocorticoid
• Maintains Na+ balance by reducing excretion of sodium from the
body
• Stimulates re-absorption of Na+ by the kidneys
• Prevents the loss of Na+ by the kidneys, sweat glands, salivary
glands and digestive system
• As a result of Na+ reabsorption there is also water reabsorption
• The retention of Na+ is accompanied by a loss of K+
• These effects will be discussed later (urinary system)
• The effect of aldosterone is the most effective when normal ADH
levels are present.
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Zona fasciculata - Glucocorticoids (Cortisol/hydrocortisone)
• This adrenal layer responds to ACTH (which endocrine glands
secretes ACTH?)
• Main hormone secreted are the Cortisol/hydrocortisone and
small amounts of corticosterone
• Glucocorticoids accelerate the rates of glucose synthesis and
glycogen formation – especially in the liver
• Adipose tissue responds by releasing fatty acids into the blood
and the tissues start to utilize fatty acids as source of energy glucose-sparing effect (which other hormone as similar effect?)
• Clucocorticoids also have anti-inflammatory effect – inhibit the
activities of WBC (use?)
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Zona reticularis Gonadocorticoids (Sex Hormones)
• Most gonadocorticoids secreted are androgens
(male sex hormones), and the most important one
is testosterone
• Androgens can be converted into estrogens after
menopause
• Both hormones from the kidney origin do not
effect sexual characteristics
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Adrenal Medulla
• Secrete epinephrine and norepinephrine
• Epinephrine is the more potent stimulator of the
heart and metabolic activities
• Norepinephrine is more influential on peripheral
vasoconstriction and blood pressure
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Epinephrine and Norepinephrine
• increase in the rate and strength of the heartbeat resulting in increased
blood pressure;
• Increase skeletal muscle strength and endurance by increasing glucose
breakdown
• Increases availability of fatty acids from adipose tissue
• Induce blood shunted from the skin and viscera to the skeletal muscles,
coronary arteries, liver, and brain;
• Cause rise in blood sugar;
• Trigger bronchi to dilate to assists in pulmonary ventilation;
• pupils dilate;
• Reduce clotting time of the blood;
• increased ACTH secretion from the anterior lobe of the pituitary.
• All of these effects prepare the body to take immediate action
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Pancreas
• A triangular gland, which has both exocrine and endocrine
cells, located behind the stomach
• Acinar cells produce an enzyme-rich juice used for digestion
(exocrine product)
• Pancreatic islets (islets of Langerhans) produce hormones
(endocrine products)
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Pancreas – islets of Langerhans cells
• The islets contain two major cell types:
• Alpha () cells that produce glucagon
• Beta () cells that produce insulin
• The islets also contain
• Delta cells – produce a peptide hormone identical to GH
inhibiting hormone (GH-IH). That hormone supresses the
release of glucagon and insulin and slows food absorptopn
and digestive enzyme secretion
• F cells – Produce the hormone pancreatic polypeptide (pp)
that inhibits gallbladder contractions and regulate the
production of some pancreatic enzymes
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Glucagon
• Major target is the liver, where it promotes
• Glycogenolysis—breakdown of glycogen to
glucose
• Gluconeogenesis—synthesis of glucose from lactic
acid and noncarbohydrates
• Release of glucose to the blood
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Glucagon
• A 29-amino-acid polypeptide hormone that is a
potent hyperglycemic agent
• Its major target is the liver, where it promotes:
• Glycogenolysis – the breakdown of glycogen to
glucose
• Gluconeogenesis – synthesis of glucose from lactic
acid and noncarbohydrates
• Release of glucose to the blood from liver cells
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Insulin
• A 51-amino-acid protein consisting of two amino acid chains
linked by disulfide bonds
• Insulin is released when glucose levels exceed normal levels (70110 mg/dl)
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http://www.chemistryexplained.com/images/chfa_02_img0437.jpg
Effects of Insulin Binding
• Insulin facilitates entry of glucose cells by binding to a membrane
receptor
• The complex insulin-receptor make a specific carrier protein
(GLUT4) available
• Once at the cell surface, GLUT4 facilitates the passive
diffusion of circulating glucose down its concentration
gradient into cells.
• Receptors for insulin are present in most cell membranes (insulindependant cells)
• Cells that lack insulin receptors are cells in the brain, kidneys,
lining of the digestive tract and RBC (insulin-independent cells).
• Those cells can absorb and utilize glucose without insulin
stimulation.
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Effects of Insulin Binding
• Insulin effects:
• Acceleration of glucose uptake as a result from an increase
of the number of glucose carrier proteins
• Acceleration of glucose utilization and increased ATP
production
• Stimulation of glycogen formation in the liver and muscle
cells
• Inhibits glycogenolysis (break down of glycogen) and
gluconeogenesis (glucose building)
• Stimulation of amino acid absorption and protein synthesis
• Stimulation of triglyceride formation in adipose tissue
• As a result glucose concentration in the blood decreases
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http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm
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Diabetes Mellitus (DM)
• Two types:
• Type I results from the destruction of beta cells and the
complete loss of insulin (hypoinsulinemia)
• Type II is the most common type (90%) and is a result of
decrease sensitivity of cells to insulin (insulin resistance).
Type II is accompanied by hyperinsulinemia (what is that?
Why?).
• Type II is associated with excess weight gain and obesity
but the mechanisms are unclear.
• Other reasons that were associated with type II diabetes:
pregnancy, polycystic ovary disease, mutations in insulin
receptors and others
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Diabetes Mellitus (DM) effects
• Increase in blood glucose due to diabetes causes
• Increase in glucose loss in urine
• Dehydration of cells – since glucose does not diffuse
through cell membrane and there is an increase in osmotic
pressure in the extracellualr fluid.
• In addition, the loss of glucose in the urine causes
osmotic diuresis - decrease in water reabsorption in the
kidney.
• The result is
• Polyuria – huge urine output and dehydration.
• Polydipsia – excessive thirst
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Diabetes Mellitus (DM) effects
• Polyphagia – excessive hunger and food consumption
because cells are starving
• Damage to blood vessels and poor blood supply to
different tissues
• Increase use of lipids as a source of energy by the cells
and increase release of keto bodies – ketosis and
changes of blood pH (acidosis). That leads to
increased respiratory rate
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http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm
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Other Hormone-Producing Structures
• Heart – produces atrial natriuretic peptide (ANP), which
reduces blood pressure, blood volume, and blood sodium
concentration
• Gastrointestinal tract – enteroendocrine cells release localacting digestive hormones
• Placenta – releases hormones that influence the course of
pregnancy
• Kidneys – secrete erythropoietin, which signals the production
of red blood cells
• Skin – produces cholecalciferol, the precursor of vitamin D
• Adipose tissue – releases leptin, which is involved in the
sensation of satiety, and stimulates increased energy
expenditure
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