THE ENDOCRINE SYSTEM

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THE ENDOCRINE SYSTEM
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Endocrine System

• Works with the nervous system to help maintain
  homeostasis.
• Works through chemicals (hormones), so its
  effects are slower to occur but tend to last
  longer than those of the nervous system.
• Hormones are distributed throughout the body by
  blood any cell with receptors is a target cell.

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Components

• Pituitary, thyroid, parathyroid, adrenal, and
  pineal glands are strictly endocrine in function.
  
• Organs that contain endocrine tissue in addition
  to other tissue heart, hypothalamus, thymus,
  pancreas, ovaries, testes, kidneys, stomach,
  liver, small intestine, skin and adipose.

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Locations and Functions
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Glands

• Endocrine glands
• Secrete directly into the interstitial fluid
  secretion may be used locally or enter blood
• Do not have ducts
• Secretions are called hormones
• Exocrine glands
• Secrete onto a surface through a duct, for
  example, a sweat gland

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Hormonal Activity

• Only about 50 hormones act in the body.
• Only a very small concentration is necessary.
• Only cells with specific receptors respond to a
  particular hormone.

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The Receptors

• A cell that has the appropriate receptors for a
  particular hormone is called a target cell.
• 2000-100,000 receptors are typically present
• Down regulation, a decrease in receptors, occurs
  when hormonal concentration is high.
• Up regulation, an increase in receptors, occurs
  when the concentration is low.

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Circulating and Local Hormones

• Endocrines circulation hormones
• Paracrines (local) act on neighboring cells
• Autocrines (local) act on the cell that
  secreted them
• Prostaglandins and leucotrienes are important
  types of local hormones

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Classes of Hormones

• Lipid soluble
• Steroids
• T3 and T4 from thyroid
• NO (also is a neurotransmitter)
• Water soluble
• Amines EPI, NE, dopamine, seratonin (all also
  neurotransmitters), histamine and melatonin
• Peptides and proteins ADH and oxytocin are
  peptides HGH and insulin are proteins TSH is a
  glycoprotein
• Eiconosoids (act as local and/or endocrine)
  prostaglandins and leucotrines

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Hormone Transport in the Blood

• Water soluble
• Circulate freely
• Fat soluble
• Must be bound to a transport protein for
  transport.
• A small amount, 0.1-10 is free fraction, and
  this is what is available to diffuse out of
  capillaries, bind to receptors, and trigger
  responses.

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Mechanisms of Action

• Response of the target cell may be
• Synthesis of a molecule e.g., insulin stimulates
  synthesis of triglycerides in adipose tissue and
  glycogen in liver cells.
• Increased permeability of plasma membrane
• Stimulation of transport of substances into or
  out of the cell
• Alteration of metabolic rates
• Contraction of smooth or cardiac muscle

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Lipid Soluble Hormones

• Require a carrier protein in blood
• Diffuse into cell freely
• Receptors are in nucleus, mitochondria and
  cytoplasm (storage)
• Activate genes which lead to synthesis of
  proteins which alter cells activity, or increase
  in aerobic respiration (mitochondria)

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Water Soluble Hormones

• Receptors are on plasma membrane
• WSHs activate a second messenger, cAMP, which,
  in turn, activates kinases.
• Kinases then phosphorylate other enzymes that
  catalyze reactions to change the cells activity.
• This happens in the cytoplasm.

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Responsiveness of the Target Cell

• Depends on hormone concentration
• Number of receptors
• Influences of other hormones
• Permissive effect-thyroxin increases effect of
  EPI on lipolysis
• Synergistic effect-both FSH and estrogen are
  necessary for oocyte development
• Antagonistic effect-insulin promotes glycogen
  synthesis by liver and glucagon promotes glycogen
  breakdown.

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Control of Secretion

• Usually hormones are released in short bursts.
• Usually a negative feedback system is in place.
  Occasionally it is a positive feedback.
• Secretion is regulated by
• Nervous system
• Blood chemistry changes, including hormone levels
• Other hormones

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The Hypothalamus

• The hypothalamus controls the pituitary gland.
  (Master of the master gland)
• The hypothalamus secretes at least nine hormones.
• Seven releasing and inhibiting hormones control
  the anterior pituitary.
• Two are stored and released by the posterior
  pituitary.

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Hypothalmic Hormones Affecting Anterior Pituitary

• Releasing hormones
• Cause specific groups of anterior pituitary cells
  to secrete their respective hormones
• Inhibiting hormones
• Cause specific groups of anterior pituitary cells
  to stop secretion of their respective hormones
• Work through negative feedback systems involving
  blood levels of hormones

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Hypothalmic Nuclei
Controls anterior pituitary
Secrets homones strored in posterior pituitary
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The Pituitary

• The pituitary gland has an anterior and a
  posterior part at maturity the pars intermedia
  atrophies during fetal development
• Anterior pituitary makes and releases seven
  hormones.
• Posterior pituitary stores and releases two
  hormones made in hypothalamus.

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Blood Supply to Posterior Pituitary

• A conventional capillary plexus, arising from
  inferior hypophyseal artery, collects the 2
  posterior pituitary hormones the hormones
  diffuse from the posterior pituitary into blood.
• The capillaries unite into the posterior
  hypophyseal veins, which deliver blood into
  systemic circulation and distribute hormones.

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Blood Supply to Hypothalamus and Anterior
Pituitary

• Capillary plexus arising from superior
  hypophyseal artery collects the 7 releasing and
  inhibiting hormones from hypothalamus.
• The capillaries unite into the the hypophyseal
  portal veins.
• Hypophyseal portal veins travel, unbranched, to
  the anterior pituiary.
• Hypophyseal portal veins give rise to a second
  capillary plexus in the anterior pituitary.

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Secondary Capillary Plexus

• Hypothalmic releasing and /or inhibiting hormones
  diffuse out of blood and affect specific cells of
  anterior pituitary.
• Anterior pituitary hormones diffuse into the
  blood of the secondary plexus
• Capillaries of secondary plexus unite into the
  anterior hypophyseal veins, which deliver blood
  into systemic circulation and distribute hormones.

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Anterior Pituitary Hormones

• Five different types of -troph cells make the
  seven anterior pituitary hormones.
• Anterior pituitary hormones enter general blood
  circulation and find their respective target
  cells in the body.
• Five of the seven A.P. influence other endocrine
  glands or tissues to produce their own hormones.
  These A.P. hormones are called tropic hormones,
  or tropins.
• hGH, FSH, LH, TSH, ACTH

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Control of Anterior Pituitary

• Releasing and inhibiting hormones from the
  hypothalamus
• Negative feedbacks involving blood levels of
  hormones from target organs
• Affect thyrotrophs, corticotrophs, gonadotrophs
• Affect hypothalamic hormones

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Negative Feedbacks
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Complex Negative Feedbacks
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The Hormones of the Anterior Pituitary

• Human growth hormone-hGH-somatotropin
• Thyroid stimulating hormone-TSH-thyrotropin
• Follicle stimulating hormone-FSH-gonadotropin
• Lutinizing hormone-LH-gonadotropin
• Adrenocorticotrophic hormone-ACTH-corticotropin
• Prolactin-PRL
• Melanocyte stimulating hormone-MSH

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Human Growth Hormone (hGH)-Somatotropin

• Produced by somatotrophs, the most numerous of
  the troph cells.
• Stimulates liver, muscle, cartilage, bone, etc.
  to make small protein hormones, called IGFs
  (somatomedins), which in turn promote cell
  growth, protein synthesis, tissue repair,
  lipolysis, and elevation of blood glucose.
• Excess hGH can cause hyperglycemia and beta cell
  damage, resulting in diabetes mellitus

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Control of hGH

• GHRH from the hypothalamus stimulates release.
• GHIH from the hypothalamus inhibits release.
• low blood glucose, low fatty acids, increased
  amino acids, deep sleep, increased sympathetic
  activity, increased glucagon, estrogen, cortisol
  and insulin promote release of hGH
• obesity, high blood glucose, increased fatty
  acids, decreased a.a., low thyroid, emotional
  deprevation, rem sleep, and high levels of hGH
  itself inhibit release.
• Control is through negative feedbacks.

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hGH and negative feedbacks
Note that negative feedbacks are typical of most
hormonal systems
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Thyroid Stimulating Hormone (TSH)-thyrotropin

• Produced by typroprophs.
• Stimulates synthesis and secretion of
  triiodothryronine and thryroxin by the thyroid
  gland (T3 and T4).
• These two hormones produced by the thyroid gland
  then enter the blood and effect the metabolism of
  all cells of the body.

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Control of TSH

• TRH from the hypothalamus stimulates release.
• GHIH inhibits release of TSH.
• Blood levels of T3.

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Follicle Stimulating Hormone (FSH)

• Produced by gonadotrophs.
• In females FSH travels via the blood from the
  anterior pituitary to the ovaries where
• Once a month it initiates the development of a
  follicle, the sac of cells containing the oocyte.
• FSH also stimulates the follicular cells to
  secrete estrogen.
• In males FSH initiates the development of sperm
  in the testes.

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Lutenizing Hormone (LH)

• Produced by gonadotrophs.
• In females LH works with FSH to stimulate
  secretion of estrogen by the follicle which
  results in the release of the secondary oocyte
  during ovulation. The secondary oocyte will
  mature further into an ovum if fertilization
  occurs.
• In females LH stimulates formation of the corpus
  luteum which secretes progesterone after
  ovulation.
• In males LH stimulates the interstitial cells to
  secrete testosterone.

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Control of FSH AND LH

• GnRH Controls both FSH and LH
• Negative feedbacks involving estrogen and inhibin
  (secreted by follicle) in females and only by
  inhibin (secreted by sertoli cells) in males
  regulate GNRH.

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Adrenocorticotropic Hormone (ACTH)-Corticotropin

• Secreted by corticotrophs
• Promotes secretion of glucocorticoids (mainly
  cortisol) in the adrenal cortex.

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Control of ACTH

• CRH from the hypothalamus promotes release.
• There is no inhibiting hormone.
• Stress, including low glucose stimulate release
  of CRH and of ACTH directly.
• Negative feedbacks affect both CRH and ACTH.

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Prolactin (PRL)

• Produced by lactotrophs.
• Initiates milk secretion by mammary glands after
  they have been primed by other hormones,
  including estrogen and progesterone.
• Milk ejection is controlled by oxytocin, a
  hormone secreted by the posterior pituitary.

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CONTROL OF PRL

• PRH and TRH promote release.
• PIH (dopamine) inhibits release.

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Melanocyte Stimulating Hormone-(MSH)

• Secreted by corticotrophs.
• Can cause skin to darken, but exact function in
  humans is unknown, but may influence brain
  activity.

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Control of MSH

• CRH stimulates release
• Dopamine inhibits release

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The Posterior Pituitary

• Stores and releases hormones produced by the
  neurosecretory cells in the hypothalamus.
• DOES NOT MAKE HORMONES.

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Posterior Pituitary Contd

• Two hormones are made in the hypothalamus
• Oxytocin
• Antidiuretic hormone
• These hormones travel in packets via fast axonal
  transport in the hypothalamohypophyseal tract.
• Nerve impulses of the axons that make up the
  tract trigger their release into the posterior
  pituitary.

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The Posterior Pituitary Hormones

• Oxytocin
• Stimulates contraction of uterus in childbirth
• Causes milk ejection
• Operates through positive feedback
• Antidiruetic hormone
• Decreases urine volume
• Raises blood pressure

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The Thyroid

• Located in the throat just inferior to larynx.
• Has 2 lobes and an isthmus between them.

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Histology of the Thyroid

• Follicles spherical sacs
• Follicular cells
• Lumen
• Thyroglobulin colloid
• Parafollicular cells
• Also called C cells

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Cells of the Thyroid

• Follicular cells
• Secrete thyroxine, also called tetraiodothyronine(
  T4), and triiodothyronine (T3). Together they
  constitute the thyroid hormones, which regulate
  metabolism.
• Parafollicular cells (C cells)
• Secrete calcitonin, which lowers blood calcium
  and phosphate levels.

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Formation, Storage and Release of Thyroid Hormones

• TSH from the pituitary stimulates production of
  the thyroid hormones.
• The thyroid hormones are formed by bonding iodine
  to the a.a. tyrosine.
• The thyroid is the only gland that stores its own
  hormones for release at a later time.

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Formation of Thyroid Hormones

• Iodine is trapped in the follicular cells as I-.
• Thyroglobulin, a high molecular glycoprotein, is
  formed in the cytoplasm, exocytosed into the
  lumen and stored there as a colloid.
• Iodine is oxidized from 2I- to I2 as it passes
  into the lumen.
• The iodine molecules react with tyrosine of the
  thyroglobulin to form monoiodothryronine, T1, and
  diiodothryronine, T2. This occurs in the lumen.
• Two T2s join to make T4, and a T1 joins with a
  T2 to make a T3. T3 is the least abundant.

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Release of T3 and T4

• Droplets of colloid reenter the follicular cells
  through pinocytosis. Lysosomes digest the
  thryroglobulin freeing the T3 and T4.
• T3 and T4 are lipid soluble and diffuse through
  the plasma membrane and enter the blood.
• The hormones, because they are lipid soluble,
  must bind to thyroxine-binding globulin for
  transport in the blood.

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Target Cells

• T3 and T4 are lipid soluble and freely enter
  target cells. Receptors are in the nucleus,
  mitochondria and cytoplasm (holds excess
  hormones in reserve).
• T4 is present in greater amounts than T3.
• T3, however, is more potent.
• Once in a cell, most T4 is converted to T3.

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Formation of Thyroid Hormones
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Feedback Systems
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Actions of thyroid hormones

• Increases basal metabolic rate
• Increased oxygen uptake
• Stimulates protein synthesis
• Increases use of glucose for ATP synthesis
• Increases lipolysis
• Enhances cholesterol excretion in bile
• Accelerates body growth
• Contributes to development of the nervous system

• Increased heart rate
• Increased sensitivity to sympathetic stimulation
• Maintenance of respiratory centers to blood gas
  levels
• Stimulation of red blood cell production
• Stimulation of other endocrine tissues
• Accelerated turnover of minerals in bone

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Increase in metabolic rate due to thyroid
hormones calorigenic effect (heat production)

• Activate genes for enzymes involved in glycolysis
  and ATP production
• Direct effect on mitochondria

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Calcitonin

• Produced by the parafollicular cells.
• Lowers blood calcium and phosphates.
• Inhibits bone reabsorption.
• Accelerates uptake of calcium and phosphates into
  bone matrix.

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The Parathyroid Glands

• Two small glands attached to the posterior of
  each lobe of the thyroid
• Principal cells
• Produce parathyroid hormone
• Oxyphil cells
• Function unknown

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Parathyroid Hormone

• Increases blood levels of calcium ion and
  magnesium ion and lowers phosphate.
• Increases bone reabsorption by osteoclasts,
  releasing calcium, magnesium and phosphate.
• Increases calcium and magnesium reabsorption by
  kidneys and phosphate excretion by kidneys.
• More phosphate is lost from kidneys than gained
  from bone blood levels drop in presence of PTH.
• Promotes calcitriol (active form of vitamin D)
  formation by kidneys.
• Increases dietary absorption of calcium,
  magnesium and phosphate.

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Calcitonin and PTH
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Calcium Ion Functions

• Skeleton
• Muscle contraction
• Nerve impulses
• Blood clotting

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Calcium Ion Imbalances

• Too high sodium ion permeabilty of plasma
  membranes decreases
• Rare
• Cell less responsive
• Too low sodium ion permeability increases
• More common
• Hyperexcitability
• Muscle spasms
• Convulsions
• Possible death

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The Adrenal Glands

• Paired glands, one on top of each kidney,
  surrounded by a capsule
• Consists of two areas
• Cortex
• The peripheral portion
• Most of the gland
• Produces steroid hormones
• Medulla
• The central portion
• Develops separately from ectoderm
• Produces epinephrine and norepinephrine, and
  dopamine(catecholamines)
• Considered a modified ANS ganglion

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Adrenal Glands
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The Cortex

• Zona glomerulosa
• Secretes mineralocorticoids
• Zona fasciculata
• Secretes glucocorticoids
• Zona reticularis
• Secretes androgens

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Mineralocorticoids (zone 1)

• At least three hormones produced in the zona
  glomerulosa. (zones)
• Help control water and electrolyte homeostasis.
• Aldosterone is the most important.

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Aldosterone Release

• In response to
• Drop in blood sodium ion
• Drop in BP
• Drop in blood volume
• Rise in blood potassium ion (very sensitive)
• RENIN-ANGIOTENSIN II-ALDOSTERONE PATHWAY

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Aldosterone

• Aldosterone acts on certain cells in the tubules
  of the kidney (they contain urine that is in the
  process of being formed).
• Aldosterone increases the reabsorption of sodium
  ion back into the blood.
• Aldosterone indirectly affects chloride ion,
  since chloride ion follows sodium ion.
• Water follows sodium and chloride ions by
  osmosis. Increase in water within vessels
  increases blood volume and blood pressure.
• Aldosterone also increases secretion of potassium
  ion and hydrogen ion into the urine from the
  blood.

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To summerize, aldosterone decreases the sodium
and chloride ion concentration in the urine, and
raises them in the blood. Water follows and
raises blood volume and blood pressure. It also
increases the potassium and hydrogen ion
concentration of the urine, and lowers their
levels in the blood.
The most important pathway through
which aldosterone is controlled is call the
RENIN-ANGIOTENSIN PATHWAY (RAA). Heres how it
works
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Effects of Aldosterone on Other Tissues

• Also causes sodium ion retention in
• Sweat
• Saliva
• Digestive secretions

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The Glucocorticoids (zone 2)

• Produced in the zona fasciculata
• Regulate metabolism and resistance to stress
• Three hormones are produced
• Cortisol most abundant and responsible for most
  of the activity
• Corticosterone
• Cortisone

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Action of Glucocorticoids

• Breakdown proteins
• Accelerates formation of glucose and glycogen
• Lipolysis
• Resistance to stress
• Anti-inflammatory effects
• Depression of immune responses

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Control of Glucocorticoids

• Low blood levels stimulate the hypothalamus to
  release CRH
• CRH and low cortisol levels directly promote
  release of ACTH (ACTH) from the anterior
  pituitary

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Feedbacks
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Androgens (zone 3)

• Secreted by the zona reticularis.
• Secreted in both males and females.
• DHEA is the major secretion.
• Contributes to sex drive
• Stimulates growth of axillary and pubic hair
• Can convert into estrogen
• Only source after menopause

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Control of Androgen Secretion

• ACTH is the main control

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The Adrenal Medulla (Medulla)

• Consists of cells called the chromaffin cells.
• Chromaffin cells receive direct innervation from
  the preganglionic cells sympathetic neurons, and
  are derived from the same embryonic germ layer.
• Consider them as specialized post ganglionic
  neurons whose secretions act as hormones instead
  of neurotransmitters.
• Because of the close affinity with the ANS large
  amounts of these hormones (above base levels of
  continuous secretion) can be released very
  quickly.

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The Hormones of the Medulla

• Epinephrine about 80
• Norepinephrine about 20
• Both are sympathomimetic that means that they
  mimic the effects of the sympathetic division of
  ANS.
• These hormones are responsible for the flight or
  fight reaction to danger.
• They also help to resist stress.
• They are not essential for life, as are the
  hormones of the cortex.

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Actions of Epinephrine and NE

• Skeletal muscle
• Accelerate hydrolysis of glycogen
• Accelerate glucose metabolism
• Adipose tissue
• Accelerate hydrolysis of triglycerides and
  release of fatty acids
• Liver
• Hydrolysis of glycogen
• Heart
• Stimulates Beta 1 receptors
• Increase in heart rate and force of contraction

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The Pancreas

• Located posterior and inferior to the stomach.
  It has a head, body and a tail.
• Has both endocrine and exocrine components.
• Most of the gland is exocrine and consists of
  clusters of cells called acini which secrete
  digestive enzymes.
• The endocrine portion, the islets of Langerhans
  or pancreatic islets, are scattered among the
  acini.

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Pancreas
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The Cells of the Islets

• Alpha
• Secrete glucagon
• Beta
• Secrete insulin
• Delta
• Secrete somatostatin
• F
• Secrete pancreatic polypeptide

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The Pancreatic Hormones

• Glucagon
• Raises blood glucose.
• Insulin
• Lowers blood glucose and allows glucose to enter
  cells where it is metabolized and its energy is
  released.
• Somatostatin
• Inhibits secretion of both glucagon and insulin
  and slows absorption of nutrients from the GI
  tract.
• Pancreatic polypeptide
• Inhibits somatostatin secretion (thereby
  encouraging release of glucagon and insulin),
  gall bladder contraction, and secretion of
  pancreatic digestive hormones.

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Insulin Pathology

• No insulin or insufficient amount results in
  diabetes mellitus.
• Insulin is completely lacking in juvenile
  diabetes and must be replaced through an
  injection. In juvenile diabetes the beta cells
  do not function.
• In adult onset diabetes the beta cells often can
  be stimulated to produce adequate amounts of
  insulin through diet and exercise or through oral
  medications.

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Control of Insulin and Glucagon

• Blood levels of glucose
• Indirect affect of any hormone that affects blood
  glucose levels e.g., hGh
• Automomic control of insulin only
• Parasympatheic
• Stimulates release of insulin
• Sympathetic
• Inhibits release of insulin

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Actions of Insulin on Cells

• Accelerates glucose uptake in all target cells
• Increases number of transport channels for
  facilitated diffusion of glucose into cell
• Accelerates glucose utilization and increases ATP
  production in all target cells
• More glucose available
• Second messenger system acivated to begin
  glycolysis
• Stimulates amino acid absorption and protein
  synthesis
• Stimulates glycogen formation in skeletal muscles
  and liver cells
• Stimulates triglyceride formation in adipose
  tissue

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Actions of glucagon on cells

• Stimulates breakdown of glycogen in skeletal
  muscle and liver cells
• Stimulates breakdown of triglycerides in adipose
  tissue
• Stimulates production of glucose in liver

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Hypoglycemia
Hypoglycemia means blood levels of glucose are
too low. This can be the result of too much
insulin. If the blood levels remain very low for
even a few minutes, severe brain damage can
result. Death can follow A person experiencing
hypoglycemia will often appear disoriented and
may pass out.
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Hyperglycemia
Hyperglycemia means that the blood levels of
glucose are too high. This is the diagnostic
element for diabetes. If levels remain very high
over a long period of time, damage to all
tissues, including the brain occur primarily due
to high osmotic pressures of blood and
interstitial fluids. DIABETIC COMA CAN RESULT.
In addition, the body uses other metabolic
pathways in lieu of the normal metabolism of
glucose (which cannot enter cells). This results
in a wasting away of the body.
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If someone is acting strangely, and you suspect
it is insulin related, more than likely the
person is hypoglycemic. Hypoglycemia can occur
rapidly, whereas the progression into diabetic
coma is prolonged. Give the person sugar to
raise blood glucose levels. If you have made a
mistake and it is, in fact, diabetic coma you are
dealing with, the blood glucose is already very
high and the additional sugar will be of little
consequence. The above applies to situations in
which you have limited knowledge about the
person. If you have a patient history and
diagnosis, or are in a hospital setting, you
should be able to make a definitive assessment of
the situation and proceed accordingly.
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Pancreas http//www.youtube.com/watch?vBtsQxUYHXb
w
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Ovaries and Testes

• Hormones produced by the gonads function both in
  reproduction and in development and maintenance
  of secondary sex characteristics.

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Ovarian Hormones

• Estrogen and progesterone
• Regulate female reproductive cycle
• Maintain pregnancy
• Prepare mammary glands for lactation
• Promote and maintain secondary sex
  characteristics
• Under control of pituitary
• Relaxin
• Allows pubic symphysis to relax during pregnancy
• Inhibin
• Inhibits FSH

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Hormones of the Testes

• Testosterone
• Stimulates descent of testes before birth
• Regulates spermatogenesis
• Promotes and maintains secondary sex
  characteristics
• Inhibin
• Inhibits FSH

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The Pineal Gland

• Attached to roof of third ventricle
• Makes melatonin
• Release is inhibited by light
• Released in dark
• Promotes sleep
• Has function in setting biological clock together
  with the suprachiasmic nucleus of the
  hypothalamus
• Has dark areas called brain sand

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Functions of melatonin

• Promotes sleep
• Circadian rythms (together with the suprachiasmic
  nucleus of the hypothalamus)
• Timining of sexual maturation
• Inhibit maturation of sperm and ova in some
  mammals
• In humans decline in melatonin production at
  puperty
• Antioxidant
• Protects against free radicles

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Thymus Gland

• Plays role in immunity through proliferation of T
  cells. Lots more on this later.

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Hormones Produced by Adipose Tissue

• Leptin
• Suppresses appetite by binding to cells of
  hypothalamus
• Must be present for release of GnRH and
  gonadotropin synthesis
• Resistin
• Reduces insulin sensitivity
• May be missing connection between type II
  diabetes obesity

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Miscellaneous Hormones

• The GI tract, placenta, kidneys, heart, and
  tissues all produce hormones.
• See book.

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STRESS AND GENERAL ADAPTATION SYNDROME

• Stress results in GAS.
• Stress can be good eustress.
• Stress can be bad distress.
• Alarm reactions involve impulses from the
  hypothalamus to the sympathetic division of ANS
  and the adrenal medulla.
• The result is the fight or flight reaction.
• If this continues over a long period of time, the
  body becomes exhausted and damaged.
• Resistance to disease decreases.

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the end