Unit XI ENDOCRINE SYSTEM

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Unit XIENDOCRINE SYSTEM
Biology 220 Anatomy Physiology I
Chapter 17, pp. 608-649
E. Gorski/ E. Lathrop-Davis/ S. Kabrhel
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Comparison of Nervous and Endocrine Systems
NOTE Nervous and endocrine systems work together
to coordinate and integrate activities of body
(homeostasis)
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Functions of Endocrine System

• 1. Reproduction
• 2. Growth and development
• 3. Response to stress
• 4. Maintenance of fluid (water), electrolyte and
  nutrient balance
• 5. Regulation of cellular metabolism and energy

4
Organs of the Endocrine System

• 1. Pituitary gland
• 2. Hypothalamus (neuroendocrine)
• 3. Pineal gland
• 4. Thyroid gland
• 5. Parathyroid gland
• 6. Thymus gland
• 7. Adrenal gland
• 8. Pancreas (also has exocrine function)
• 9. Gonads (testes or ovaries - also have exocrine
  functions)

Fig. 17.4, p.616
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Topics

• Hormone
• Types
• Modes of Action
• Target cell activation
• Control
• Specific glands, their hormones, and disorders
• Pituitary
• Thyroid
• Parathyroid
• Adrenal
• Pancreas
• Thymus
• Gonads (testes and ovaries)
• General Adaptation Syndrome

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Hormones

• chemicals
• secreted by endocrine gland cells into blood (by
  way of interstitial fluid)
• regulate metabolic functions of other cells
  (called target cells)
• carried to all cells, but action is specific to
  cells that have receptors for the hormone
• specificity of bodys response to hormone depends
  on how many cells have the receptor (highly
  specific if few cells respond e.g., ACTH
  diffuse action if many respond e.g., thyroxine)

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Chemical Types of Hormones

• Amino-acid based (amino acids, short or long
  peptides, proteins)
• e.g., insulin, growth hormone, prolactin
• Steroids - lipid derivatives of cholesterol
• e.g., hormones from gonads (testosterone,
  estrogen)
• e.g., hormones from adrenal cortex
  (adrenocortical hormones)
• Eicosanoids - locally-secreted, locally-acting
  hormones secreted by all cell membranes (e.g.,
  prostaglandins, which increase blood pressure and
  contribute to uterine contraction)

8
Types of Changes in Target Cells

• plasma membrane permeability changes (opening of
  protein channels may change membrane potential)
• activation of genes for increased protein
  synthesis, including enzymes
• activation or deactivation of enzymes already
  present
• secretion of cellular products
• stimulation of cell division (mitosis)

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Mechanisms of Action

• action in target cell depends on receptor
• receptor may be
• in plasma membrane
• second messenger mechanisms
• used by most amino acid-based hormones (water
  soluble)
• intracellular (in cytoplasm or nucleus)
• direct gene activation
• used by steroids and thyroid hormones (lipid
  soluble)

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Mechanisms of Action Steroids

• bind to intracellular receptors
• hormone diffuses through plasma membrane and
  makes its way to nucleus
• gt where it binds with intracellular receptor to
  form hormone-receptor complex
• gt hormone-receptor complex interacts with
  chromatin (DNA) to affect gene activity (turn
  genes on or off)
• gt synthesis of mRNA
• gt synthesis of protein

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Steroid Signaling
Fig. 17.2, p. 613
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Mechanism of ActionThyroid Hormone

• similar to mechanism for steroid hormones
• diffuses across plasma membrane
• diffuses into nucleus where it interacts with
  intracellular receptors to activate genes for
  proteins (enzymes) involved in cellular
  respiration (glycolysis)
• also, binds to receptors at mitochondria to
  activate genes for proteins involved in cellular
  respiration (Krebs cycle and electron transport
  chain)

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Mechanisms of Action Other Hormones

• plasma membrane receptor
• used by most amino acid-based hormones
• interaction of hormone with plasma membrane
  receptor results in activation of second
  messenger systems (cyclic AMP or PIP-calcium)
• activation of second messenger has cascade effect
  resulting in
• enzyme activation, or
• membrane permeability changes or secretion

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Membrane Receptor Mechanisms1. Cyclic AMP
(cAMP) Signaling

• interaction of hormone with receptor
• gt activates G protein (cleaves phosphate from
  GTP)-gt excitation
• gt G protein activates adenylate cyclase
• gt adenylate cyclase forms cAMP from ATP
• gt cAMP activates protein kinases
• gt protein kinases activate (or inhibit) other
  proteins by phosphorylation
• gt cAMP degraded by enzyme
• slightly different G protein inactivates
  adenylate cyclase - associated with different
  hormone receptor
• Link to animation http//student.ccbc.cc.md.us/c_
  anatomy/animat/cAMP.htm

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cAMP Signaling Mechanism
Fig. 17.1, p. 611
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Membrane Receptor Mechanisms2. PIP-Calcium
Signaling

• interaction of hormone with receptor --gt
  activates membrane-bound enzyme phospholipase
• gt phospholipase cleaves PIP2 (phosphatidyl
  inositol diphosphate) into diacylglycerol (DAG)
  and IP3 -- each of which acts as a second
  messenger
• diacylglycerol (DAG) activates protein kinases
• IP3 (inositol triphosphate) causes release of
  Ca2 into cytoplasm (from endoplasmic reticulum
  or other storage areas) --gt Ca2 acts as third
  messenger

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PIP-Calcium Mechanism (cont)

• -gt Ca2 (third messenger)
• changes enzyme activity and plasma membrane
  channels, or
• binds to calmodulin (intracellular regulatory
  protein) --gt activates enzymes
• see Fig. 17.2 for examples of proteins that act
  through membrane-receptors and 2nd messengers

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PIP-Calcium Signaling Mechanism
Fig. 17.1, p. 612
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Factors Affecting Target Cell Activation

• a. blood levels of hormone, which depend on
• rate of hormone release
• rate of deactivation (by target cell or liver)
• b. affinity of hormone for receptor
• greater affinity means greater association --gt
  greater effect
• c. number of receptors available

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Factors Affecting Target Cell Activation (cont)

• c. number of receptors available
• up-regulation increase in blood level of
  specific hormone (normally present at low levels)
  causes cells to make more receptors
• down-regulation prolonged exposure to high level
  of specific hormone --gt cells remove some
  receptors
• --gtreturn to normal response level
• cross-regulation influence of one hormone on
  number of receptors for another hormone e.g.,
  progesterone causes uterus to make fewer estrogen
  receptors estrogen causes uterus to make more
  progesterone receptors

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Hormone Removal

• hormones may be
• degraded by specific enzymes within target cells
• removed from blood by kidneys (excreted in urine)
• degraded by liver (excreted in urine and feces)
• half-life - time for 1/2 of hormone to be removed
  (from a fraction of a minute to 30 minutes)
• onset - time from release to action (minutes
  amino acid-based to days steroids)
• duration of action - how long the effects last
  (20 minutes to several hours)

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Control of Hormone Release

• Humoral control
• Neural control
• Hormonal control

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Control of Hormone Release Humoral

• Hormone released in response to changing blood
  levels of ion or nutrient (negative feedback)

• parathyroid glands detects low blood Ca2 ? PTH
  ? raises blood Ca2
• thyroid (parafollicular cells) detect high blood
  Ca2--gtcalcitonin--gtdecrease blood Ca2

Fig.17.3, p615
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Control of Hormone Release Humoral

• Other examples
• pancreas
• beta cells detect high blood glucose ? insulin ?
  decreases blood glucose
• alpha cells detect low blood glucose ?glucagon ?
  raises blood glucose
• zona glomerulosa (of adrenal cortex) detects low
  blood Na or high blood K ? aldosteronetthy, ?
  K

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Control of Hormone Release Neural

• Hormone released in response to nerve impulse

• preganglionic fibers of sympathetic division ?
  stimulate release of catecholamines (epinephrine,
  norepinephrine) from adrenal medulla

• impulses from hypothalamus result in release of
  oxytocin or ADH from posterior pituitary

Fig. 17.3, p. 615
Fig. 17.5, p. 617
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Control of Hormone Release Hormonal

• Hormone produced by one endocrine gland (or
  hypothalamus) affects secretion of hormone by
  another endocrine gland
• hypothalamus acts as overall coordinator ?
  releases regulatory hormones (releasing hormones
  or inhibitory hormones) ? affects anterior
  pituitary
• anterior pituitary, when stimulated, secretes
  hormones that affect other glands (e.g., TSH
  thyroid stimulating hormone stimulates release
  of thyroid hormones from thyroid gland)

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Hormonal Control Role of Hypothalamus

• Releasing hormones from hypothalamus stimulate
  secretion from anterior pituitary
• Inhibitory hormones from hypothalamus inhibit
  secretion by anterior pituitary
• Impulses from hypothalamus cause release of
  hormones from posterior pituitary

Fig. 17.5, p. 617
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Hormone Control - Misc.

• nervous system can override normal endocrine
  control
• e.g., in fight-or-flight response, sympathetic
  impulses result in release of epinephrine and
  norepinephrine from adrenal medulla --gt increases
  blood glucose levels to maintain fuel supply
  during stress or exertion (overrules effect of
  insulin on blood glucose level)

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Organs of the Endocrine System and Their Products

• The following major glands will be covered one at
  a time with their products
• 1. Pituitary gland / Hypothalamus
• 2. Thyroid gland
• 3. Parathyroid gland
• 4. Adrenal gland
• 5. Pancreas (also has exocrine function)
• 6. Gonadal hormones (ovaries and testes)
• 7. Thymus

Fig. 17.4, p. 616
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1. Pituitary Gland (Hypophysis)

• located in sella turcica of sphenoid bone (in
  cranial cavity), inferior to hypothalamus
• consists of two lobes
• A. neurohypophysis ( posterior pituitary)
• attached to hypothalamus by infundibulum
• contains axons and axon terminals of
  neurosecretory cells whose cell bodies are in
  hypothalamic nuclei
• B. adenohypophysis ( anterior pituitary)
• consists of glandular epithelium

http//www.usc.edu/hsc/dental/ghisto/end/c_1.html
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Pituitary Development
From roof of mouth
http//calloso.med.mun.ca/tscott/head/pit.htm
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A. Neurohypophysis (Posterior Pituitary)

• consists of nerve fibers (axons of neurosecretory
  cells with cell bodies in hypothalamus) and
  pituicytes (glial cells that support nerve
  fibers)
• acts primarily as a storage and releasing area
  for hormones actually made in hypothalamic nuclei
• hormones released in response to impulses from
  hypothalamus (neural control)
• hormones are short amino acid chains (peptides)
• oxytocin
• antidiuretic hormone (ADH or vasopressin)

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A. NeurohypophysisOxytocin (OT)

• action, in pregnant or nursing women
• stimulates contraction of smooth muscle of
  uterine wall during labor and delivery
• stimulates ejection of milk in lactating mothers
• action, in men and non-pregnant women, may be
  involved in sexual arousal and orgasm

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A. NeurohypophysisOxytocin (OT)

• control
• during labor/delivery, positive feedback
  stretching of uterus/cervix --gt sensory impulses
  to hypothalamus --gt increased secretion of OT --gt
  increased contraction
• suckling sucking of infant on breast --gt sensory
  to hypothalamus --gt oxytocin release --gt release
  of milk

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A. Neurohypophysis Antidiuretic Hormone (ADH)

• action antidiuretic hormone (ADH) directly
  affects blood pressure - acts as powerful
  vasoconstrictor --gt increases blood pressure
  (hence name vasopressin)
• action affects water balance (indirect affect on
  blood pressure) - acts on tubules of kidney to
  increase reabsorption of water ? less water lost
  in urine

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A. Neurohypophysis ADH

• disorders
• hyposecretion due to damage of hypothalamic
  nucleus or neurohypophysis--gt diabetes insipidus
  - excessive urine production (polyuria) and
  thirst
• hypersecretion --gt SIADH (syndrome of
  inappropriate ADH secretion) - water retention,
  headache, cerebral edema, weight gain,
  hypoosmolarity

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Antidiuretic Hormone (ADH) Control

• neural control increased electrolyte (NaCl)
  concentration --gt affects (supraoptic) nucleus in
  hypothalamus --gt impulse to neurohypophysis --gt
  release of ADH --gt increased water reabsorption
  --gt decrease in electrolyte concentration
• other stimuli pain, low BP, morphine,
  barbiturates, nicotine, aldosterone (hormone from
  adrenal cortex - hormonal control)
• inhibition alcohol (results in more urine
  production and, potentially, dehydration)
• diuretic drugs - some act to supress ADH
  secretion used to treat hypertension and
  congestive heart failure

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B. Adenohypophysis (Anterior Pituitary)

• linked to hypothalamus via hypophyseal portal
  system (capillary networks and small veins)
• carries regulatory hormones from hypothalamus to
  pituitary
• releasing hormones stimulate secretion of
  pituitary hormones
• inhibitory hormones inhibit secretion
• consists of epithelial cells
• all hormones produced are proteins
• tropic hormones - affect some endocrine glands or
  provide maintenance oversight for other organs

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B. AdenohypophysisGrowth Hormone (GH)

• highest levels during evening and sleep
• action stimulates increased rate of protein
  synthesis leading to cell growth and division
• bones and skeletal muscle respond more than other
  body cells
• action stimulates use of fat as energy source
  and decreases rate of glucose uptake and glucose
  metabolism (diabetogenic effect spares
  glucose)
• control
• release stimulated by GHRH (growth hormone
  releasing hormone) from hypothalamus
• inhibited by GHIH (from hypothalamus) and
  somatomedins (produced by liver under GH
  stimulation)

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Growth Hormone (GH) Disorders

• Disorders
• hypersecretion
• gigantism (in children)
• up to 8 tall, normal body proportions
• acromegaly (after epiphyseal plates close)
• enlargement of extremities and face, thickening
  of soft tissue
• hyposecretion
• pituitary dwarfism - in children, up to 4 tall
• progeria - premature aging, atrophy of body
  tissues

See Fig. 17.6, p. 619
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B. Adenohypophysis Prolactin (PRL)

• action
• stimulates milk production in mammary glands
• helps stimulate development of mammary glands
  (along with other hormones)
• in males, may help regulate testosterone
  production
• control
• stimulation PRH (prolactin-releasing hormone
  from hypothalamus), high estrogens,
  breast-feeding
• inhibition PIH (hypothalamus), stimulated by
  rising PRL levels, low estrogen

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B. AdenohypophysisProlactin (PRL)

• Disorders
• hyperprolactinemia hypersecretion due to
  adenohypophyseal tumors results in galactorrhea,
  lack of menses and infertility in women,
  impotence in men

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B. Adenohypophysis Thyroid-Stimulating Hormone
(TSH)

• TSH thyrotropin
• action
• stimulates secretion of hormones from thyroid
  gland (T4 and T3) also stimulates development of
  thyroid in youth
• control
• release stimulated by TRH (thyroid releasing
  hormone from hypothalamus)
• inhibited by rising levels of thyroid hormones
  and by GHIH

44
B. Adenohypophysis Adrenocorticotropic hormone
(ACTH)

• ACTHcorticotropin
• action stimulates release of hormones from
  adrenal cortex
• control
• release stimulated by CRH (corticotropin-releasing
  hormone from hypothalamus)
• release inhibited by rising levels of
  glucocorticoids from adrenal cortex

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B. AdenohypophysisGonadotropins

• regulate activity and secretion by gonads (testes
  in males ovaries in females)
• control
• stimulated by GnRH (gonadotropin-releasing
  hormone from hypothalamus)
• release of GnRH is inhibited by rising levels of
  estrogens, progestins and androgens
  (testosterone)
• two important hormones
• FSH
• LH

46
GonadotropinsFollicle-Stimulating Hormone (FSH)

• action
• females (ovaries) - stimulates development of
  ovarian follicles and estrogen production
• males (testes) - stimulates sperm production and
  development
• inhibited by inhibin and testosterone from testes
  (feedback to hypothalamus and anterior pituitary)
  and estrogen, progesterone and inhibin from
  ovaries (feedback to anterior pituitary)

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GonadotropinsLuteinizing Hormone (LH)

• LHlutropin
• action
• females (ovaries) - induces ovulation stimulates
  secretion of estrogens and progestins (e.g.,
  progesterone)
• males (testes) - stimulates production of
  androgens (e.g., testosterone )
• inhibited by estrogen, progesterone and inhibin
  form ovaries (feedback to anterior pituitary) and
  by inhibin and testosterone from testes (feedback
  to hypothalamus and anterior pituitary)

48
2. Thyroid Gland

• located anteriorly in cervical region, just
  inferior to thyroid cartilage two lobes
  connected by thin isthmus
• largest purely endocrine gland in body
• consists of follicles (cuboidal or simple
  squamous epithelium) filled with colloid
  (combination of protein thyroglobulin
  containing amino acid tyrosine building block of
  thyroid hormones)
• parafollicular cells produce calcitonin

http//www.usc.edu/hsc/dental/ghisto/end/c_26.html
49
2. Thyroid Gland T4 and T3

• hormones based on amino acid tyrosine (differ in
  number of iodine ions)
• thyroxine (tetraiodothyronine T4) and
• triiodothyronine (T3)
• T3 is 10x more active, but less common (T4
  accounts for about 90 of all thyroid hormone)
• much T4 converted to T3 by liver, kidneys, some
  other tissues

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2. Thyroid Gland T4 and T3

• affect metabolic rate of every cell in the body,
  except brain, spleen, testes, uterus and thyroid
  gland
• affect other activities within these organs and
  glands
• readily cross membranes (diffuse through plasma
  membrane to bind to mitochondrial receptors and
  receptors in nucleus)

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2. Thyroid Gland
Fig. 17.8, p. 625
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T4 and T3 Actions

• increase synthesis of enzymes involved in
  cellular respiration --gt increase basal metabolic
  rate
• increases glucose oxidation --gt ATP synthesis
• increases ATP synthesis in cytoplasm and by
  mitochondria
• results in increased heat production (calorigenic
  effect)
• work with GH to promote normal tissue growth and
  development, especially important to
  growth/development of CNS, skeletal and
  reproductive systems

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T4 and T3 Control

• release stimulated by TSH (thyroid-stimulating
  hormone from adenohypophysis)
• release of TSH stimulated by TRH from
  hypothalamus
• release of TRH is stimulated by cold, pregnancy,
  low thyroxine
• release inhibited by GHIH, high glucocorticoid
  levels, high sex hormone levels, high iodine

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Hypothyroidism

• too little thyroid hormone (thyroid gland defect,
  inadequate TSH, TRH, or iodine)
• Hashimotos thyroid autoimmune disorder in
  which thyroid is attacked and function decreases
• myxedema - low BMR, constipation, puffy eyes,
  edema, lethargy, mental sluggishness
• endemic goiter - enlargement of thyroid gland
  usually due to lack of sufficient iodine
• cretinism - genetic deficiency of thyroid gland
  or lack of dietary iodine during development
  resulting in mental retardation, disproportionate
  growth, short body with thick tongue and neck
• treatment - reversed by iodine supplements or
  hormone replacement therapy

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Hyperthyroidism

• too much thyroid hormone (thyrotoxicosis)
• Graves disease - autoimmune disease in which
  abnormal antibodies similar to TSH mimic its
  function and continuously stimulate release of
  thyroid hormones results in high BMR, sweating,
  rapid heart rate, weight loss, restlessness, mood
  shifts, fatigues easily, limited energy also
  toxic goiter
• exophthalmos - protrusion of eyeballs, fibrous
  tissue become edematous (swollen)
• treatments - removal of thyroid gland or
  irradiation
• patient must be on synthetic thyroid hormone the
  rest of his/her life

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2. Thyroid Gland Calcitonin (CT)

• polypeptide produced by parafollicular cells
• actions decreases blood calcium levels by
• stimulating osteoblasts (Ca2 uptake and
  incorporation into bone)
• inhibiting osteoclast activities (osteoclasts
  break down bone matrix releasing calcium)
• control responds directly to blood calcium
  levels
• very rapid effect
• probably more important during childhood when it
  stimulates bone growth
• important because at high blood Ca2, membranes
  become less permeable to Na

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3. Parathyroid Glands

• 2 paired structures on posterior of thyroid gland
• oxyphyil cells - function unknown
• chief cells secrete parathyroid hormone (PTH
  protein)
• actions increases blood Ca2 by
• stimulating osteoclast activity (which break down
  bone matrix) while inhibiting osteoblasts (which
  form bone matrix)
• stimulating increased reabsorption of Ca2 by
  kidney
• indirectly stimulating increased absorption of
  Ca2 by small intestine by causing secretion of
  calcitrol form kidneys

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3. Parathyroid Glands
Fig. 17.10, p. 628
Fig. 17.11, p. 629
http//www.usc.edu/hsc/dental/ghisto/end/c_32.html
59
Hyperparathyroidism

• rare caused by parathyroid gland tumor
• results in hypercalcemia (excess Ca2 levels in
  blood) --gt depression of nervous system (because
  of effect on sodium permeability), abnormal
  reflexes, skeletal muscle weakness, nausea,
  vomiting, kidney stones, calcium deposits in soft
  tissues bones become soft

60
Hypoparathyroidism

• trauma to or removal of parathyroid gland
• results in hypocalcemia (low blood Ca2) --gt
  neurons become too excitable --gt muscle tetany
  --gt spasms/cramps --gt respiratory paralysis --gt
  death

61
4. Adrenal Glands

• located in abdominal cavity against back wall
  (retroperitoneal), superior to kidney
• surrounded by connective tissue capsule
• two regions
• cortex - outer region, glandular, three zones
• zona glomerulosa - outer zone
• zona fasciculata - middle zone
• zona reticularis - inner zone

• medulla - inner region, modified neural tissue
  (develops from same tissue in embryo as
  ganglionic postganglionic neurons of
  sympathetic division)

62
4. Adrenal Gland Development
http//sprojects.mmi.mcgill.ca/embryology/ug/Adren
al_Stuff/Normal/zones.html
63
4. Adrenal Gland Regions and Zones
Fig. 17.12, p. 630
64
Adrenal Cortex Zona Glomerulosa

• produces steroid hormones based on cholesterol
• mineralocorticoids - ion (and water) balance
• main hormone is aldosterone
• action
• stimulates reabsorption of Na and secretion of
  K from kidney, sweat glands, salivary glands,
  pancreas
• secondarily, increases water reabsorption in
  kidney (water follows Na)

65
Adrenal Cortex Zona Glomerulosa

• control
• aldosterone release stimulated by
• high K, low Na
• angiotensin II (result of renin-angiotensin
  pathway stimulated by low blood pressure),
• ACTH (when under severe stress)
• inhibited by low K, high Na

Fig. 17.13, p. 632
66
Adrenal Cortex Zona Glomerulosa

• Disorders
• aldosteronism hypersecretion (adrenal tumor)
• increased water and Na reabsorption --gt
  hypertension, edema
• loss of K --gt disruption of neural and muscle
  function

67
Adrenal Cortex Zona Glomerulosa

• Disorders
• Addisons Disease hyposecretion glucocorticoids
  and mineralocorticoids
• results in decreased Na and water reabsorption,
  increased blood K --gt low blood volume --gt
  hypotension, dehydration
• changes in membrane potentials --gt disruption in
  neural and muscular function
• also decreased cortisol secretion by zona
  fasciculata --gt decreased blood glucose levels
  (especially during prolonged stress)

68
Adrenal Cortex Zona Fasciculata

• glucocorticoids - effects on glucose metabolism
• main hormone is cortisol (hydrocortisone)
• actions
• maintains blood glucose levels, especially in
  times of stress, by
• promoting gluconeogenesis (making new glucose in
  liver) and use of alternative fuels by other
  cells (saves glucose for the brain)
• anti-inflammatory decrease immune response
• can be used clinically to treat allergic
  reactions (e.g., poison ivy), rheumatoid arthritis

69
Adrenal Cortex Zona Fasciculata

• Control
• stimulated by ACTH
• inhibited by cortisol (inhibits secretion of CRH
  from hypothalamus)
• blood levels peak in the morning
• Disorders
• Addisons Disease
• - hyposecretion of glucocorticoids and
  mineralocorticoids

70
Zona Fasciculata Cushings Disease

• hypersecretion of glucocorticoids
• caused by hypersecretion of ACTH due to tumor in
  ZF, pituitary, lungs, kidneys, or pancreas
• suppresses glucose metabolism resulting in
• hyperglycemia (elevated glucose steroid
  diabetes),
• stimulates lipid metabolism (weight loss),
• loss of muscle and bone mass,
• buffalo neck and moon face (fat
  redistribution),
• anti-inflammatory effects (mask infection)
• water and salt retention (effect of aldosterone
  hypersecretion --gt water retention --gt
  hypertension)

71
Adrenal Cortex Zona Reticularis

• gonadocorticoids
• most are androgens (male sex hormones) -
  converted to testosterone small amounts of
  estrogens
• actions may contribute to onset of puberty
  (levels rise between 7 and 13 years of age exact
  function compared to hormones from ovaries or
  testes unclear)
• control stimulated by ACTH

72
Adrenal Cortex Zona Reticularis

• hypersecretion results in
• masculinization and masculine pattern of hair
  distribution in females
• in males - rapid maturation of reproductive
  organs, secondary sex characteristics
  hypersecretion of estrogens causes feminization
  and gynecomastia (enlarged breasts)

73
Adrenal Medulla

• chromaffin cells (modified neurons - arise from
  same embryonic tissue as postganglionic neurons
  of sympathetic division)
• catecholamines - epinephrine (80), norepi (NE)
• control secretion stimulated by preganglionic
  fibers of sympathetic nerves during
  flight-or-fight response

74
Adrenal Medulla

• actions
• epinephrine (more potent) - increases HR (beta
  receptors), bronchodilation (in lungs), increased
  blood glucose (breakdown of glycogen in liver and
  skeletal muscle, and breakdown of adipose tissue)
• NE - peripheral vasoconstriction --gt increased BP

75
5. Pancreas

• has both exocrine (acini secrete digestive
  enzymes) and endocrine function (islets of
  Langerhans)
• control responds to blood glucose levels
  (humoral)
• hormones are polypeptides (proteins)

http//www.usc.edu/hsc/dental/ghisto/end/c_49.html
76
5. Pancreas

• major cell types
• alpha cells secrete glucagon
• beta cells secrete insulin
• delta cells secrete somatostatin (which inhibits
  insulin and glucagon secretion, and decrease fat
  absorption in intestines)
• F cells regulate exocrine function of pancreas
  (secrete pancreatic polypeptide)

77
5. Pancreas Glucagon

• actions hyperglycemic (increases blood glucose)
• stimulates formation and release of glucose from
  liver (main target)
• glycogenolysis - breakdown of glycogen (storage
  form of glucose)
• gluconeogenesis - formation of glucose from
  noncarbohydrate molecules (e.g., amino acids,
  glycerol, lactic acid)
• stimulates glycogenolysis in skeletal muscle
• stimulates triglyceride breakdown in adipose
  tissue (fat mobilization)

78
5. Pancreas Glucagon

• control
• secreted in response to low blood sugar, rising
  amino acid levels in blood
• inhibited by increased blood glucose and by
  somatostatin

79
5. Pancreas Insulin

• actions hypoglycemic (lowers blood glucose)
• increases transport of glucose into muscle and
  fat cells (NOTE does not increase uptake by
  brain, liver, or kidney)
• inhibits breakdown of glycogen and formation of
  glucose from amino acids or fatty acids (inhibits
  glycogenolysis and gluconeogenesis)
• promotes formation of glycogen (liver, skeletal
  muscles), protein synthesis (muscle), and fat
  synthesis and storage (adipose)

80
5. Pancreas Insulin (Control)

• stimulated by
• increased blood glucose
• increased blood amino acid and fatty acid levels
• parasympathetic impulses
• hyperglycemic hormones (GH, glucagon,
  epinephrine, thyroxine, glucocorticoids)
  indirectly result in insulin secretion by
  increasing blood glucose levels
• inhibited by
• low blood glucose and by somatostatin
• sympathetic impulses

Fig. 17.17, p. 637
81
5. Pancreas Insulin - Disorders Diabetes
Mellitus (DM)

• hyposecretion (or hypoactivity) of insulin
• body cells not stimulated to take up glucose
• hyperglycemia (excess blood glucose)
• very high glucose --gt nausea --gt fight-or-flight
  response --gt secretion of hyperglycemic hormones
  (epi, NE adrenal medulla, glucocorticoids
  adrenal cortex) --gt stimulates gluconeogenesis,
  lipolysis, glycogenolysis --gt adds to already
  high glucose
• not all sugar reabsorbed from urine --gt glucose
  lost in urine (glucosuria) --gt increased water
  loss --gt excessive urine production (polyuria)
  and excessive thirst (polydipsia)

82
5. Pancreas Insulin - Diabetes Mellitus

• cells use fats as energy source (due to poor
  glucose uptake)
• hyperglycemic hormones stimulate fat mobilization
  --gt fats in blood (lipidemia) --gt increase in
  lipid metabolites in blood (ketone bodies, which
  are strong organic acids) --gt decrease blood pH
  (ketoacidosis) and ketone bodies in urine
  (ketonuria)
• decreased blood pH --gt severe depression of
  nervous system --gt deep breathing --gt diabetic
  coma --gt death
• polyphagia (excessive hunger) - final sign, due
  to use of fats and proteins as energy sources

83
Type I Diabetes mellitus

• also called insulin-dependent diabetes (IDDM
  formerly juvenile onset diabetes)
• onset is sudden, usually before age 15
• may be due to autoimmune attack of proteins in
  beta cells (see A Closer Look, p. 640-641)
• result is lack of insulin activity
• lipidemia (high blood lipid content) and
  increased cholesterol lead to long-term vascular
  problems (arteriosclerosis, strokes, heart
  attacks, renal shutdown, gangrene, blindness)
• treated with insulin injections or pancreatic
  islet transplant (newer technique)

84
Type II Diabetes Mellitus

• non-insulin-dependent (NIDDM formerly
  mature-onset diabetes)
• usually starts after age 40
• insulin levels are normal or elevated, but
  peripheral tissue become less sensitive to it
• 25-30 of Americans carry gene that predisposes
  them to NIDDM, more likely in over-weight people
  (90 of cases)
• adipose cells secrete tumor necrosis factor alpha
  that depresses production of protein needed for
  glucose uptake
• often controllable with diet and exercise

85
Hyperinsulinism

• excess of insulin (usually from injection of
  excess)
• causes hypoglycemia --gt secretion of
  hyperglycemic hormones (to raise blood glucose)
  -? low glucose to brain --gt anxiety, nervousness,
  tremors, weakness --gt eventually, disorientation,
  convulsions, death due to insulin shock
• treated by providing sugar source

86
6. Gonadal Hormones

• Female - ovaries
• produce/secrete estrogens and progesterone
• estrogens alone --gt development and maintenance
  of ovaries, uterus, secondary sex characteristics
• estrogens with progesterone --gt breast
  development, uterine cycle

http//www.lab.anhb.uwa.edu.au/mb140/CorePages/Fem
aleRepro/femalerepro.htmFollicles
87
6. Gonadal Hormones

• Male - testes
• produce androgens (testosterone) --gt development
  and maintenance of male reproductive system and
  secondary sex characteristics sperm production,
  protein synthesis
• inhibin - inhibits release of FSH and LH

http//www.usc.edu/hsc/dental/ghisto/rep/c_72.html
88
7. Thymus

• located in mediastinum
• function
• active during childhood and before puberty,
• after puberty gradually decreases in size and
  becomes fibrous (involution)
• secretes thymosin (thymic extract containing
  several complementary hormones)
• action promotes development and maturation of
  lymphocytes
• gradual decrease in size and secretory abilities
  make the elderly more susceptible to disease

89
General Adaptation Syndrome (GAS)

• stress response
• stress any condition that threatens to alter
  homeostasis
• same general response to a variety of stress
• major endocrine player is adrenal gland (medulla
  and cortex)
• three phases
• alarm
• resistance
• exhaustion

90
GAS Alarm Phase

• immediate response to stress
• mobilization of energy sources
• sympathetic division activated results in release
  of epinephrine, NE from adrenal medulla

91
GAS Alarm Phase

• direct neural and epinephrine effects
• increased heart rate
• dilation of pupils
• changes in circulation (more to skeletal
  cardiac muscle, less to gut)
• increased respiration
• increased energy use by cells
• increased blood glucose
• decreased digestion and urine production
• increased perspiration

92
GAS Resistance Phase

• when stress is present more than a few hours,
  able to cope for weeks to a few months
• secretion of renin from kidney --gt
  renin-angiotensin pathway --gt aldosterone
  secretion --gt increased Na reabsorption --gt
  increased water retention
• secretion of ACTH from pituitary
• increased aldosterone secretion
• increased glucocorticoid secretion --gt increased
  blood glucose, conservation of glucose by muscle,
  lipids and proteins mobilized as alternative
  energy sources
• secretion of glucose conservation hormones
  (growth hormone, thyroid hormone, epi) --gt
  conservation of glucose and use of alternatives

93
GAS Exhaustion Phase

• prolonged stress (more than a few months)
• homeostatic breakdown due to
• mineral (electrolyte) imbalances
• depletion of glucocorticoids
• exhaustion of lipid reserves (especially with
  starvation)
• structural or functional damage to organs

94
Adrenal Gland Role in GAS
Fig. 17.15, p. 635