1. The Endocrine System

2. Endocrine System: Overview
Acts with nervous system to coordinate and integrate activity of body cells
Influences metabolic activities via hormones transported in blood
Response slower but longer lasting than nervous system
Endocrinology
Study of hormones and endocrine organs
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3. Endocrine System: Overview
Controls and integrates
Reproduction
Growth and development
Maintenance of electrolyte, water, and nutrient balance of blood
Regulation of cellular metabolism and energy balance
Mobilization of body defenses
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4. Endocrine System: Overview
Exocrine glands
Nonhormonal substances (sweat, saliva)
Have ducts to carry secretion to membrane surface
Endocrine glands
Produce hormones
Lack ducts
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5. Endocrine System: Overview
Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands
Hypothalamus is neuroendocrine organ
Some have exocrine and endocrine functions
Pancreas, gonads, placenta
Other tissues and organs that produce hormones
Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart
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6. Pineal gland Hypothalamus Pituitary gland Thyroid gland
Figure Location of selected endocrine organs of the body.
Pineal gland
Hypothalamus
Pituitary gland
Thyroid gland
Parathyroid glands
(on dorsal aspect
of thyroid gland)
Thymus
Adrenal glands
Pancreas
Gonads
• Ovary (female)
• Testis (male)
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7. Hormones: long-distance chemical signals; travel in blood or lymph
Chemical Messengers
Hormones: long-distance chemical signals; travel in blood or lymph
Autocrines: chemicals that exert effects on same cells that secrete them
Paracrines: locally acting chemicals that affect cells other than those that secrete them
Autocrines and paracrines are local chemical messengers; not considered part of endocrine system
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8. Chemistry of Hormones Two main classes Amino acid-based hormones
Amino acid derivatives, peptides, and proteins
Steroids
Synthesized from cholesterol
Gonadal and adrenocortical hormones
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9. Mechanisms of Hormone Action
Though hormones circulate systemically only cells with receptors for that hormone affected
Target cells
Tissues with receptors for specific hormone
Hormones alter target cell activity
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10. Mechanisms of Hormone Action
Hormone action on target cells may be to
Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels
Stimulate synthesis of enzymes or other proteins
Activate or deactivate enzymes
Induce secretory activity
Stimulate mitosis
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11. Mechanisms of Hormone Action
Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location
Water-soluble hormones (all amino acid–based hormones except thyroid hormone)
Act on plasma membrane receptors
Act via G protein second messengers
Cannot enter cell
2. Lipid-soluble hormones (steroid and thyroid hormones)
Act on intracellular receptors that directly activate genes
Can enter cell
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12. Plasma Membrane Receptors and Second-messenger Systems
cAMP signaling mechanism:
Hormone (first messenger) binds to receptor
Receptor activates G protein
G protein activates adenylate cyclase
Adenylate cyclase converts ATP to cAMP (second messenger)
cAMP activates protein kinases that phosphorylate proteins
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13. Plasma Membrane Receptors and Second-messenger Systems
cAMP signaling mechanism
Activated kinases phosphorylate various proteins, activating some and inactivating others
cAMP is rapidly degraded by enzyme phosphodiesterase
Intracellular enzymatic cascades have huge amplification effect
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14. Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones.
Slide 1
Recall from Chapter 3 that
G protein signaling mechanisms
are like a molecular relay race.
Hormone
(1st messenger)
Receptor
G protein
Enzyme
2nd
messenger
Hormone (1st messenger) binds receptor. 1
Adenylate cyclase
Extracellular fluid
G protein (Gs)
cAMP
cAMP activates protein kinases. 5
GTP
Receptor
GTP
ATP
GDP
Inactive
protein
kinase
Active
protein
kinase
GTP
Triggers responses of
target cell (activates
enzymes, stimulates
cellular secretion,
opens ion channel, etc.)
Cytoplasm
Receptor activates G protein (Gs). 2
G protein activates adenylate cyclase. 3
Adenylate
cyclase converts
ATP to cAMP (2nd messenger). 4
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15. Plasma Membrane Receptors and Second-messenger Systems
PIP2-calcium signaling mechanism
Involves G protein and membrane-bound effector – phospholipase C
Phospholipase C splits PIP2 into two second messengers – diacylglycerol (DAG) and inositol trisphosphate (IP3)
DAG activates protein kinase; IP3 causes Ca2+ release
Calcium ions act as second messenger
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16. Plasma Membrane Receptors and Second-messenger Systems
Ca2+ alters enzyme activity and channels, or binds to regulatory protein calmodulin
Calcium-bound calmodulin activates enzymes that amplify cellular response
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17. Other Signaling Mechanisms
Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones
Some work without second messengers
E.g., insulin receptor is tyrosine kinase enzyme that autophosphorylates upon insulin binding  docking for relay proteins that trigger cell responses
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18. Intracellular Receptors and Direct Gene Activation
Steroid hormones and thyroid hormone
Diffuse into target cells and bind with intracellular receptors
Receptor-hormone complex enters nucleus; binds to specific region of DNA
Prompts DNA transcription to produce mRNA
mRNA directs protein synthesis
Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell
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19. Cytoplasm Nucleus mRNA New protein
Figure Direct gene activation mechanism of lipid-soluble hormones.
Slide 1
Steroid
hormone
Extracellular
fluid
Plasma
membrane
The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. 1
Cytoplasm
Receptor
protein
Receptor-
hormone
complex
The receptor-
hormone complex enters the nucleus. 2
Receptor
Binding region
Nucleus
The receptor- hormone complex binds a specific DNA region. 3
DNA
Binding initiates transcription of the gene to mRNA. 4
mRNA
The mRNA directs protein synthesis. 5
New protein
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20. Target Cell Specificity
Target cells must have specific receptors to which hormone binds, for example
ACTH receptors found only on certain cells of adrenal cortex
Thyroxin receptors are found on nearly all cells of body
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21. Target Cell Activation
Target cell activation depends on three factors
Blood levels of hormone
Relative number of receptors on or in target cell
Affinity of binding between receptor and hormone
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22. Target Cell Activation
Hormones influence number of their receptors
Up-regulation—target cells form more receptors in response to low hormone levels
Down-regulation—target cells lose receptors in response to high hormone levels
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23. Control of Hormone Release
Blood levels of hormones
Controlled by negative feedback systems
Vary only within narrow, desirable range
Endocrine gland stimulated to synthesize and release hormones in response to
Humoral stimuli
Neural stimuli
Hormonal stimuli
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24. Humoral Stimuli
Changing blood levels of ions and nutrients directly stimulate secretion of hormones
Example: Ca2+ in blood
Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone)
PTH causes Ca2+ concentrations to rise and stimulus is removed
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25. Hormone release caused by altered levels of certain critical ions or
Figure 16.4a Three types of endocrine gland stimuli.
Slide 1
Humoral Stimulus
Hormone release caused by altered
levels of certain critical ions or
nutrients.
Capillary (low Ca2+
in blood)
Thyroid gland
(posterior view)
Parathyroid
glands
Parathyroid
glands
PTH
Stimulus: Low concentration of Ca2+ in
capillary blood.
Response: Parathyroid glands secrete
parathyroid hormone (PTH), which
increases blood Ca2+.
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26. Nerve fibers stimulate hormone release
Neural Stimuli
Nerve fibers stimulate hormone release
Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines
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27. Hormone release caused by neural input.
Figure 16.4b Three types of endocrine gland stimuli.
Slide 1
Neural Stimulus
Hormone release caused by neural input.
CNS (spinal cord)
Preganglionic
sympathetic
fibers
Medulla of
adrenal gland
Capillary
Stimulus: Action potentials in preganglionic
sympathetic fibers to adrenal medulla.
Response: Adrenal medulla cells secrete
epinephrine and norepinephrine.
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28. Hormones stimulate other endocrine organs to release their hormones
Hormonal Stimuli
Hormones stimulate other endocrine organs to release their hormones
Hypothalamic hormones stimulate release of most anterior pituitary hormones
Anterior pituitary hormones stimulate targets to secrete still more hormones
Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from final target organs inhibit release of anterior pituitary hormones
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29. Hormone release caused by another hormone (a tropic hormone).
Figure 16.4c Three types of endocrine gland stimuli.
Slide 1
Hormonal Stimulus
Hormone release caused by another
hormone (a tropic hormone).
Hypothalamus
Anterior
pituitary
gland
Thyroid
gland
Adrenal
cortex
Gonad
(Testis)
Stimulus: Hormones from hypothalamus.
Response: Anterior pituitary gland secretes
hormones that stimulate other endocrine glands to secrete hormones.
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30. Nervous System Modulation
Nervous system modifies stimulation of endocrine glands and their negative feedback mechanisms
Example: under severe stress, hypothalamus and sympathetic nervous system activated
 body glucose levels rise
Nervous system can override normal endocrine controls
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31. Hormones circulate in blood either free or bound
Hormones in the Blood
Hormones circulate in blood either free or bound
Steroids and thyroid hormone are attached to plasma proteins
All others circulate without carriers
Concentration of circulating hormone reflects
Rate of release
Speed of inactivation and removal from body
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32. Hormones removed from blood by
Hormones in the Blood
Hormones removed from blood by
Degrading enzymes
Kidneys
Liver
Half-life—time required for hormone's blood level to decrease by half
Varies from fraction of minute to a week
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33. Onset of Hormone Activity
Some responses ~ immediate
Some, especially steroid, hours to days
Some must be activated in target cells
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34. Duration of Hormone Activity
Limited
Ranges from 10 seconds to several hours
Effects may disappear as blood levels drop
Some persist at low blood levels
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35. Interaction of Hormones at Target Cells
Multiple hormones may act on same target at same time
Permissiveness: one hormone cannot exert its effects without another hormone being present
Synergism: more than one hormone produces same effects on target cell  amplification
Antagonism: one or more hormones oppose(s) action of another hormone
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36. The Pituitary Gland and Hypothalamus
Pituitary gland (hypophysis) has two major lobes
Posterior pituitary (lobe)
Neural tissue
Anterior pituitary (lobe) (adenohypophysis)
Glandular tissue
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37. Pituitary-hypothalamic Relationships
Posterior pituitary (lobe)
Downgrowth of hypothalamic neural tissue
Neural connection to hypothalamus (hypothalamic-hypophyseal tract)
Nuclei of hypothalamus synthesize neurohormones oxytocin and antidiuretic hormone (ADH)
Neurohormones are transported to and stored in posterior pituitary
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38. Paraventricular nucleus
Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2).
Slide 1
Paraventricular nucleus
Hypothalamus 1
Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).
Posterior lobe
of pituitary
Optic
chiasma
Supraoptic
nucleus
Infundibulum
(connecting stalk) 2
Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.
Inferior
hypophyseal
artery
Hypothalamic-
hypophyseal
tract
Axon terminals 3
Oxytocin and ADH are stored in axon terminals in the posterior pituitary.
Posterior lobe
of pituitary 4
Oxytocin
ADH
When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.
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39. Pituitary-hypothalamic Relationships
Anterior Lobe:
Originates as outpocketing of oral mucosa
Vascular connection to hypothalamus
Hypophyseal portal system
Primary capillary plexus
Hypophyseal portal veins
Secondary capillary plexus
Carries releasing and inhibiting hormones to anterior pituitary to regulate hormone secretion
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40. they stimulate or inhibit
Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2).
Slide 1
Hypothalamus
Hypothalamic
neurons synthesize
GHRH, GHIH, TRH,
CRH, GnRH, PIH.
Anterior lobe
of pituitary
Superior
hypophyseal
artery
When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus. 1 2
Hypothalamic hormones travel through portal veins to the anterior pituitary where
they stimulate or inhibit
release of hormones made in the anterior pituitary.
Hypophyseal
portal system
• Primary capillary
plexus
In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation. 3
A portal system is two capillary plexuses (beds) connected by veins.
• Hypophyseal
portal veins
• Secondary
capillary plexus
GH, TSH, ACTH,
FSH, LH, PRL
Anterior lobe
of pituitary
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41. Posterior Pituitary and Hypothalamic Hormones
Oxytocin and ADH
Each composed of nine amino acids
Almost identical – differ in two amino acids
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42. Strong stimulant of uterine contraction Released during childbirth
Oxytocin
Strong stimulant of uterine contraction
Released during childbirth
Hormonal trigger for milk ejection
Acts as neurotransmitter in brain
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43. Inhibits or prevents urine formation Regulates water balance
ADH (Vasopressin)
Inhibits or prevents urine formation
Regulates water balance
Targets kidney tubules  reabsorb more water
Release also triggered by pain, low blood pressure, and drugs
Inhibited by alcohol, diuretics
High concentrations  vasoconstriction
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44. Syndrome of inappropriate ADH secretion (SIADH)
Diabetes insipidus
ADH deficiency due to hypothalamus or posterior pituitary damage
Must keep well-hydrated
Syndrome of inappropriate ADH secretion (SIADH)
Retention of fluid, headache, disorientation
Fluid restriction; blood sodium level monitoring
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45. Anterior Pituitary Hormones
Growth hormone (GH)
Thyroid-stimulating hormone (TSH) or thyrotropin
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin (PRL)
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46. Anterior Pituitary Hormones
All are proteins
All except GH activate cyclic AMP second-messenger systems at their targets
TSH, ACTH, FSH, and LH are all tropic hormones (regulate secretory action of other endocrine glands)
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47. Growth Hormone (GH, or Somatotropin)
Produced by somatotropic cells
Direct actions on metabolism
Increases blood levels of fatty acids; encourages use of fatty acids for fuel; protein synthesis
Decreases rate of glucose uptake and metabolism – conserving glucose
 Glycogen breakdown and glucose release to blood (anti-insulin effect)
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48. Growth Hormone (GH, or Somatotropin)
Indirect actions on growth
Mediates growth via growth-promoting proteins – insulin-like growth factors (IGFs)
IGFs stimulate
Uptake of nutrients  DNA and proteins
Formation of collagen and deposition of bone matrix
Major targets—bone and skeletal muscle
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49. GH release chiefly regulated by hypothalamic hormones
Growth Hormone (GH)
GH release chiefly regulated by hypothalamic hormones
Growth hormone–releasing hormone (GHRH)
Stimulates release
Growth hormone–inhibiting hormone (GHIH) (somatostatin)
Inhibits release
Ghrelin (hunger hormone) also stimulates release
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50. Homeostatic Imbalances of Growth Hormone
Hypersecretion
In children results in gigantism
In adults results in acromegaly
Hyposecretion
In children results in pituitary dwarfism
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51. Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH).
Hypothalamus
secretes growth
hormone–releasing
hormone (GHRH), and
GHIH (somatostatin)
Feedback
Inhibits GHRH release
Stimulates GHIH release
Anterior
pituitary
Inhibits GH synthesis
and release
Growth hormone (GH)
Indirect actions
(growth-
promoting)
Direct actions
(metabolic,
anti-insulin)
Liver and
other tissues
Produce
Insulin-like growth
factors (IGFs)
Effects
Effects
Fat
metabolism
Carbohydrate
metabolism
Skeletal
Extraskeletal
Increases, stimulates
Reduces, inhibits
Increased protein
synthesis, and
cell growth and
proliferation
Initial stimulus
Increased cartilage
formation and
skeletal growth
Increased
fat breakdown
and release
Increased blood
glucose and other
anti-insulin effects
Physiological response
Result
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52. Figure 16.7 Disorders of pituitary growth hormone.
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53. Thyroid-stimulating Hormone (Thyrotropin)
Produced by thyrotropic cells of anterior pituitary
Stimulates normal development and secretory activity of thyroid
Release triggered by thyrotropin-releasing hormone from hypothalamus
Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus
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54. Hypothalamus TRH Anterior pituitary TSH Thyroid gland
Figure 16.8 Regulation of thyroid hormone secretion.
Hypothalamus
TRH
Anterior pituitary
TSH
Thyroid gland
Thyroid
hormones
Stimulates
Target cells
Inhibits
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55. Adrenocorticotropic Hormone (Corticotropin)
Secreted by corticotropic cells of anterior pituitary
Stimulates adrenal cortex to release corticosteroids
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56. Adrenocorticotropic Hormone (Corticotropin)
Regulation of ACTH release
Triggered by hypothalamic corticotropin-releasing hormone (CRH) in daily rhythm
Internal and external factors such as fever, hypoglycemia, and stressors can alter release of CRH
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57. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
Gonadotropins
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
Secreted by gonadotropic cells of anterior pituitary
FSH stimulates gamete (egg or sperm) production
LH promotes production of gonadal hormones
Absent from the blood in prepubertal boys and girls
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58. Regulation of gonadotropin release
Gonadotropins
Regulation of gonadotropin release
Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty
Suppressed by gonadal hormones (feedback)
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59. Secreted by prolactin cells of anterior pituitary
Prolactin (PRL)
Secreted by prolactin cells of anterior pituitary
Stimulates milk production
Role in males not well understood
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60. Regulation of PRL release
Prolactin (PRL)
Regulation of PRL release
Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine)
Blood levels rise toward end of pregnancy
Suckling stimulates PRL release and promotes continued milk production
Hypersecretion causes inappropriate lactation, lack of menses, infertility in females, and impotence in males
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61. Two lateral lobes connected by median mass called isthmus
Thyroid Gland
Two lateral lobes connected by median mass called isthmus
Composed of follicles that produce glycoprotein thyroglobulin
Colloid (fluid with thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone
Parafollicular cells produce the hormone calcitonin
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62. Figure 16.9 The thyroid gland.
Hyoid bone
Colloid-filled
follicles
Thyroid cartilage
Epiglottis
Follicular cells
Superior thyroid
artery
Common carotid
artery
Inferior thyroid
artery
Isthmus of
thyroid gland
Trachea
Left subclavian
artery
Left lateral
lobe of thyroid
gland
Aorta
Parafollicular cells
Gross anatomy of the thyroid gland, anterior view
Photomicrograph of thyroid gland
follicles (145x)
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63. Actually two related compounds
Thyroid Hormone (TH)
Actually two related compounds
T4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms
T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms
Affects virtually every cell in body
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64. Major metabolic hormone
Thyroid Hormone
Major metabolic hormone
Increases metabolic rate and heat production (calorigenic effect)
Regulation of tissue growth and development
Development of skeletal and nervous systems
Reproductive capabilities
Maintenance of blood pressure
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65. Synthesis of Thyroid Hormone
Thyroid gland stores hormone extracellularly
Thyroglobulin synthesized and discharged into follicle lumen
Iodides (I–) actively taken into cell and released into lumen
Iodide oxidized to iodine (I2),
Iodine attaches to tyrosine, mediated by peroxidase enzymes
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66. Synthesis of Thyroid Hormone
Iodinated tyrosines link together to form T3 and T4
Colloid is endocytosed and vesicle is combined with a lysosome
T3 and T4 are cleaved and diffuse into bloodstream
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67. Figure 16.10 Synthesis of thyroid hormone.
Slide 1
Thyroid follicular cells
Colloid
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Tyrosines (part of thyroglobulin
molecule)
Capillary
Iodine is attached to tyrosine in colloid, forming DIT and MIT. 4
Golgi
apparatus
Rough ER
Thyro-
globulin
colloid
Iodine
Iodide is oxidized to iodine. 3
DIT
MIT
Iodide (I−)
Iodide (I–) is trapped (actively transported in). 2 T4
Iodinated tyrosines are linked together to form T3 and T4. 5 T3
Lysosome T4
Thyroglobulin colloid is endocytosed and combined with a lysosome. 6 T3
Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream. 7 T4
Colloid in
lumen of
follicle T3
To peripheral tissues
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68. Transport and Regulation of TH
T4 and T3 transported by thyroxine-binding globulins (TBGs)
Both bind to target receptors, but T3 is ten times more active than T4
Peripheral tissues convert T4 to T3
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69. 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 negative feedback during pregnancy or exposure to cold
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70. Hypothalamus TRH Anterior pituitary TSH Thyroid gland
Figure Regulation of thyroid hormone secretion.
Hypothalamus
TRH
Anterior pituitary
TSH
Thyroid gland
Thyroid
hormones
Stimulates
Target cells
Inhibits
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71. Homeostatic Imbalances of TH
Hyposecretion in adults—myxedema; goiter if due to lack of iodine
Hyposecretion in infants—cretinism
Hypersecretion—most common type is Graves' disease
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72. Figure 16.11 Thyroid disorders.
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73. Produced by parafollicular (C) cells
Calcitonin
Produced by parafollicular (C) cells
No known physiological role in humans
Antagonist to parathyroid hormone (PTH)
At higher than normal doses
Inhibits osteoclast activity and release of Ca2+ from bone matrix
Stimulates Ca2+ uptake and incorporation into bone matrix
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74. Four to eight tiny glands embedded in posterior aspect of thyroid
Parathyroid Glands
Four to eight tiny glands embedded in posterior aspect of thyroid
Contain oxyphil cells (function unknown) and parathyroid cells that secrete parathyroid hormone (PTH) or parathormone
PTH—most important hormone in Ca2+ homeostasis
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75. Capillary Parathyroid cells (secrete parathyroid hormone) Oxyphil
Figure The parathyroid glands.
Pharynx
(posterior
aspect)
Capillary
Parathyroid
cells
(secrete
parathyroid
hormone)
Thyroid
gland
Parathyroid
glands
Esophagus
Oxyphil
cells
Trachea
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76. Negative feedback control: rising Ca2+ in blood inhibits PTH release
Parathyroid Hormone
Functions
Stimulates osteoclasts to digest bone matrix and release Ca2+ to blood
Enhances reabsorption of Ca2+ and secretion of phosphate by kidneys
Promotes activation of vitamin D (by kidneys); increases absorption of Ca2+ by intestinal mucosa
Negative feedback control: rising Ca2+ in blood inhibits PTH release
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77. Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine.
Hypocalcemia
(low blood Ca2+)
PTH release from
parathyroid gland
Osteoclast activity
in bone causes Ca2+
and PO43- release
into blood
Ca2+ reabsorption
in kidney tubule
Activation of
vitamin D by kidney
Ca2+ absorption
from food in small
intestine
Ca2+ in blood
Initial stimulus
Physiological response
Result
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78. Homeostatic Imbalances of PTH
Hyperparathyroidism due to tumor
Bones soften and deform
Elevated Ca2+ depresses nervous system and contributes to formation of kidney stones
Hypoparathyroidism following gland trauma or removal or dietary magnesium deficiency
Results in tetany, respiratory paralysis, and death
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79. Adrenal (Suprarenal) Glands
Paired, pyramid-shaped organs atop kidneys
Structurally and functionally are two glands in one
Adrenal medulla—nervous tissue; part of sympathetic nervous system
Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids
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80. Three layers of cortex produce the different corticosteroids
Adrenal Cortex
Three layers of cortex produce the different corticosteroids
Zona glomerulosa—mineralocorticoids
Zona fasciculata—glucocorticoids
Zona reticularis—gonadocorticoids
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81. Figure 16.14 Microscopic structure of the adrenal gland.
Hormones
secreted
Capsule
Zona
glomerulosa
Aldosterone
Zona
fasciculata
Adrenal gland
• Medulla
Cortex
• Cortex
Cortisol
and
androgens
Kidney
Zona
reticularis
Medulla
Adrenal
medulla
Epinephrine
and
norepinephrine
Drawing of the histology of the
adrenal cortex and a portion of
the adrenal medulla
Photomicrograph (115x)
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82. Regulate electrolytes (primarily Na+ and K+) in ECF
Mineralocorticoids
Regulate electrolytes (primarily Na+ and K+) in ECF
Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions
Importance of K+: sets RMP of cells
Aldosterone most potent mineralocorticoid
Stimulates Na+ reabsorption and water retention by kidneys; elimination of K+
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83. Aldosterone Release triggered by
Decreasing blood volume and blood pressure
Rising blood levels of K+
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84. Mechanisms of Aldosterone Secretion
Renin-angiotensin-aldosterone mechanism: decreased blood pressure stimulates kidneys to release renin  triggers formation of angiotensin II, a potent stimulator of aldosterone release
Plasma concentration of K+: increased K+ directly influences zona glomerulosa cells to release aldosterone
ACTH: causes small increases of aldosterone during stress
Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion to decrease blood pressure
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85. water; increased K+ excretion
Figure Major mechanisms controlling aldosterone release from the adrenal cortex.
Primary regulators
Other factors
Blood volume
and/or blood
pressure
K+ in blood
Stress
Blood pressure
and/or blood
volume
Hypo-
thalamus
Heart
Kidney
CRH
Direct
stimulating
effect
Anterior
pituitary
Renin
Initiates
cascade
that
produces
ACTH
Atrial natriuretic
peptide (ANP)
Angiotensin II
Inhibitory
effect
Zona glomerulosa
of adrenal cortex
Enhanced
secretion
of aldosterone
Targets
kidney tubules
Absorption of Na+ and
water; increased K+ excretion
Blood volume
and/or blood pressure
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86. Homeostatic Imbalances of Aldosterone
Aldosteronism—hypersecretion due to adrenal tumors
Hypertension and edema due to excessive Na+
Excretion of K+ leading to abnormal function of neurons and muscle
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87. Keep blood glucose levels relatively constant
Glucocorticoids
Keep blood glucose levels relatively constant
Maintain blood pressure by increasing action of vasoconstrictors
Cortisol (hydrocortisone)
Only one in significant amounts in humans
Cortisone
Corticosterone
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88. Glucocorticoids: Cortisol
Released in response to ACTH, patterns of eating and activity, and stress
Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins
Promotes rises in blood glucose, fatty acids, and amino acids
"Saves" glucose for brain
Enhances vasoconstriction  rise in blood pressure to quickly distribute nutrients to cells
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89. Homeostatic Imbalances of Glucocorticoids
Hypersecretion—Cushing's syndrome/disease
Depresses cartilage and bone formation
Inhibits inflammation
Depresses immune system
Disrupts cardiovascular, neural, and gastrointestinal function
Hyposecretion—Addison's disease
Also involves deficits in mineralocorticoids
Decrease in glucose and Na+ levels
Weight loss, severe dehydration, and hypotension
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90. Same patient with Cushing's syndrome. The white arrow shows
Figure The effects of excess glucocorticoid.
Patient before onset.
Same patient with Cushing's
syndrome. The white arrow shows
the characteristic "buffalo hump" of
fat on the upper back.
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91. Gonadocorticoids (Sex Hormones)
Most weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens
May contribute to
Onset of puberty
Appearance of secondary sex characteristics
Sex drive in women
Estrogens in postmenopausal women
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92. Gonadocorticoids Hypersecretion
Adrenogenital syndrome (masculinization)
Not noticeable in adult males
Females and prepubertal males
Boys – reproductive organs mature; secondary sex characteristics emerge early
Females – beard, masculine pattern of body hair; clitoris resembles small penis
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93. Adrenal Medulla
Medullary chromaffin cells synthesize epinephrine (80%) and norepinephrine (20%)
Effects
Vasoconstriction
Increased heart rate
Increased blood glucose levels
Blood diverted to brain, heart, and skeletal muscle
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94. Adrenal Medulla Responses brief
Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and heart
Norepinephrine influences peripheral vasoconstriction and blood pressure
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95. Adrenal Medulla Hypersecretion Hyposecretion
Hyperglycemia, increased metabolic rate, rapid heartbeat and palpitations, hypertension, intense nervousness, sweating
Hyposecretion
Not problematic
Adrenal catecholamines not essential to life
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96. Short-term stress Prolonged stress
Figure Stress and the adrenal gland.
Short-term stress
Prolonged stress
Stress
Nerve impulses
Hypothalamus
CRH (corticotropin-
releasing hormone)
Spinal cord
Corticotropic cells
of anterior pituitary
Preganglionic
sympathetic
fibers
To target in blood
Adrenal cortex
(secretes steroid
hormones)
Adrenal medulla
(secretes amino acid–
based hormones)
ACTH
Catecholamines
(epinephrine and
norepinephrine)
Mineralocorticoids
Glucocorticoids
Short-term stress response
Long-term stress response
• Heart rate increases
• Kidneys retain
sodium and water
• Proteins and fats converted
to glucose or broken down
for energy
• Blood pressure increases
• Bronchioles dilate
• Blood volume and
blood pressure
rise
• Liver converts glycogen to glucose and releases
glucose to blood
• Blood glucose increases
• Immune system
supressed
• Blood flow changes, reducing digestive system activity
and urine output
• Metabolic rate increases
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97. Pineal Gland Small gland hanging from roof of third ventricle
Pinealocytes secrete melatonin, derived from serotonin
Melatonin may affect
Timing of sexual maturation and puberty
Day/night cycles
Physiological processes that show rhythmic variations (body temperature, sleep, appetite)
Production of antioxidant and detoxification molecules in cells
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98. Triangular gland partially behind stomach
Pancreas
Triangular gland partially behind stomach
Has both exocrine and endocrine cells
Acinar cells (exocrine) produce enzyme-rich juice for digestion
Pancreatic islets (islets of Langerhans) contain endocrine cells
Alpha () cells produce glucagon (hyperglycemic hormone)
Beta () cells produce insulin (hypoglycemic hormone)
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99. Pancreatic islet •  (Glucagon- producing) cells •  (Insulin-
Figure Photomicrograph of differentially stained pancreatic tissue.
Pancreatic islet
•  (Glucagon-
producing)
cells
•  (Insulin-
producing)
cells
Pancreatic acinar
cells (exocrine)
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100. Causes increased blood glucose levels Effects
Glucagon
Major target—liver
Causes increased blood glucose levels
Effects
Glycogenolysis—breakdown of glycogen to glucose
Gluconeogenesis—synthesis of glucose from lactic acid and noncarbohydrates
Release of glucose to blood
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101. Not needed for glucose uptake in liver, kidney or brain
Insulin
Effects of insulin
Lowers blood glucose levels
Enhances membrane transport of glucose into fat and muscle cells
Inhibits glycogenolysis and gluconeogenesis
Participates in neuronal development and learning and memory
Not needed for glucose uptake in liver, kidney or brain
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102. Insulin Action on Cells
Activates tyrosine kinase enzyme receptor
Cascade  increased glucose uptake
Triggers enzymes to
Catalyze oxidation of glucose for ATP production – first priority
Polymerize glucose to form glycogen
Convert glucose to fat (particularly in adipose tissue)
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103. BALANCE: Normal blood glucose level (about 90 mg/100 ml)
Figure Insulin and glucagon from the pancreas regulate blood glucose levels.
Stimulates glucose
uptake by cells
Insulin
Tissue cells
Stimulates
glycogen
formationw
Pancreas
Glucose
Glycogen
Blood
glucose
falls to
normal
range.
Liver
IMBALANCE
Stimulus
Blood
glucose level
BALANCE: Normal blood glucose level (about 90 mg/100 ml)
Stimulus
Blood
glucose level
IMBALANCE
Blood
glucose
rises to
normal
range.
Pancreas
Glucose
Glycogen
Liver
Stimulates
glycogen
breakdown
Glucagon
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104. Factors That Influence Insulin Release
Elevated blood glucose levels – primary stimulus
Rising blood levels of amino acids and fatty acids
Release of acetylcholine by parasympathetic nerve fibers
Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids
Somatostatin; sympathetic nervous system
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105. Homeostatic Imbalances of Insulin
Diabetes mellitus (DM)
Due to hyposecretion (type 1) or hypoactivity (type 2) of insulin
Blood glucose levels remain high  nausea  higher blood glucose levels (fight or flight response)
Glycosuria – glucose spilled into urine
Fats used for cellular fuel  lipidemia; if severe  ketones (ketone bodies) from fatty acid metabolism  ketonuria and ketoacidosis
Untreated ketoacidosis  hyperpnea; disrupted heart activity and O2 transport; depression of nervous system  coma and death possible
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106. Diabetes Mellitus: Signs
Three cardinal signs of DM
Polyuria—huge urine output
Glucose acts as osmotic diuretic
Polydipsia—excessive thirst
From water loss due to polyuria
Polyphagia—excessive hunger and food consumption
Cells cannot take up glucose; are "starving"
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107. Homeostatic Imbalances of Insulin
Hyperinsulinism:
Excessive insulin secretion
Causes hypoglycemia
Low blood glucose levels
Anxiety, nervousness, disorientation, unconsciousness, even death
Treated by sugar ingestion
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108. Table 16.4 Symptoms of Insulin Deficit (Diabetes Mellitus)
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109. Ovaries and Placenta Gonads produce steroid sex hormones
Same as those of adrenal cortex
Ovaries produce estrogens and progesterone
Estrogen
Maturation of reproductive organs
Appearance of secondary sexual characteristics
With progesterone, causes breast development and cyclic changes in uterine mucosa
Placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)
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110. Testes produce testosterone
Initiates maturation of male reproductive organs
Causes appearance of male secondary sexual characteristics and sex drive
Necessary for normal sperm production
Maintains reproductive organs in functional state
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111. Other Hormone-producing Structures
Adipose tissue
Leptin – appetite control; stimulates increased energy expenditure
Resistin – insulin antagonist
Adiponectin – enhances sensitivity to insulin
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112. Other Hormone-producing Structures
Enteroendocrine cells of gastrointestinal tract
Gastrin stimulates release of HCl
Secretin stimulates liver and pancreas
Cholecystokinin stimulates pancreas, gallbladder, and hepatopancreatic sphincter
Serotonin acts as paracrine
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113. Other Hormone-producing Structures
Heart
Atrial natriuretic peptide (ANP) decreases blood Na+ concentration, therefore blood pressure and blood volume
Kidneys
Erythropoietin signals production of red blood cells
Renin initiates the renin-angiotensin-aldosterone mechanism
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114. Other Hormone-producing Structures
Skeleton (osteoblasts)
Osteocalcin
Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling; reduces body fat
Activated by insulin
Low levels of osteocalcin in type 2 diabetes – perhaps increasing levels may be new treatment
Skin
Cholecalciferol, precursor of vitamin D
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115. Other Hormone-producing Structures
Thymus
Large in infants and children; shrinks as age
Thymulin, thymopoietins, and thymosins
May be involved in normal development of T lymphocytes in immune response
Classified as hormones; act as paracrines
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116. Developmental Aspects
Hormone-producing glands arise from all three germ layers
Most endocrine organs operate well until old age
Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone function
Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutants
Interference with glucocorticoids may help explain high cancer rates in certain areas
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117. Developmental Aspects
Ovaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur
Testosterone also diminishes with age, but effect is not usually seen until very old age
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118. Developmental Aspects
GH levels decline with age - accounts for muscle atrophy with age
TH declines with age, contributing to lower basal metabolic rates
PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH
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