1. ENDOCRINE SYSTEM 1

2. ENDOCRINE SYSTEM Endocrine system Composed of glands
“Ductless glands”
Secrete chemical signals into the bloodstream
(Exocrine glands secrete substances through ducts to surfaces)
Secretory products are hormones

3. HORMONES Hormones Chemical signal (“ligand”)
Produced in minute amounts by a collection of cells
Secreted into the interstitial spaces
Enters the circulatory system
Transported throughout the body
Influences the activity of specific tissues
“Target tissues”

4. REGULATION
Endocrine and nervous systems both regulate the activities of structures within the body
Accomplished in different ways
Hormones are amplitude-modulated signals
Signals consist mainly of increases or decreases in the concentration of hormones in body fluids
Response produced within several seconds to hours
Action potentials are frequency-modulated signals
Action potentials vary in frequency but not in amplitude
Response produced within milliseconds

5. REGULATION Nervous and endocrine systems are intimately related
The two systems cannot be completely separated either anatomically or functionally
e.g., Some neurons secrete neurohormones into the circulatory system
Function like hormones
e.g., Some neurons directly innervate endocrine glands and influence their secretory activity
e.g., Some hormones secreted by endocrine glands affect the nervous system and influence its activity

6. CHEMICAL SIGNALS
Intercellular chemical signals allow cells to communicate with each other
e.g., Neurotransmitters, neuromodulators, and hormones
There are various types of intercellular signals
Autocrine chemical signals
Paracrine chemical signals
Pheromones

7. CHEMICAL SIGNALS Autocrine chemical signals
Released by cells and have an effect on similar cells
e.g., Prostaglandins are released by smooth muscle cells and platelets in response to inflammation
Causes aggregation of platelets and relaxation of blood vessel smooth muscle

8. CHEMICAL SIGNALS Paracrine chemical signals
Released by cells and affect other cell types locally without being transported in the blood
e.g., The peptide somatostatin is released by cells in the pancreas and functions locally to inhibit the secretion of insulin from other cells of the pancreas

9. CHEMICAL SIGNALS Pheromones
Secreted into the environment and modify the behavior and physiology of other individuals
e.g., Pheromones released in urine of cats and dogs signal fertility
e.g., Pheromones released by women influence the menstrual cycles of other women

10. CHEMICAL SIGNALS Many intercellular chemical signals consistently
Intercellular signals
Many consistently fit one specific definition
Many do not consistently fit one specific definition
e.g., Norepinephrine functions both as a neurotransmitter and a neurohormone

13. HORMONE STRUCTURE Three main classes of hormones
Polymers of amino acids
Proteins or polypeptides
Glycoprotein hormones contain carbohydrate components
Derivatives of single amino acids
Lipids
Steroids or derivatives of fatty acids

16. SECRETION Most hormones are not secreted at a constant rate
Secretion increases and decreases dramatically over time
Secretion rate generally controlled by negative feedback
Body activity regulated is maintained within normal range
Homeostasis is maintained
Secretion is sometimes regulated by positive feedback
Less frequent
e.g., components of the female reproductive system
Estrogen stimulates LH secretion
LH stimulates estrogen secretion

17. SECRETION Three major patterns of regulation
Changes in the extracellular concentration of a non-hormone molecule can affect an endocrine gland
Neural control of the endocrine gland
Control of hormone secretion by another hormone or neurohormone
Regulation of hormone secretion often involves more than one of these mechanisms

18. SECRETION
Changes in the extracellular concentration of a non-hormone molecule can affect an endocrine gland
e.g., Blood glucose levels affect insulin secretion from the pancreas
Insulin increases glucose movement into cells
Insulin secretion decreases

19. SECRETION Neural control of the endocrine gland
Neurons synapse with hormone-producing cells
Neurotransmitter release stimulates or inhibits hormone release
e.g., Stress or exercise stimulates the adrenal gland to secrete epinephrine and norepinephrine

20. SECRETION
Control of hormone secretion by another hormone or neurohormone
e.g., Thyroid-releasing hormone (TRH) from the hypothalamus stimulates the secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary gland
TSH stimulates the secretion of thyroid hormones (T3 & T4)
etc.

21. SECRETION
Some hormones are in the circulatory system at relatively constant levels
e.g., Thyroid hormones
Levels of some hormones change suddenly in response to certain stimuli
e.g., Epinephrine is released in response to stress or exercise
Levels of some hormones change in relatively constant cycles
e.g., Reproductive hormones cycle in women during their reproductive years

22. SECRETION
Some hormones are in the circulatory system at relatively constant levels
e.g., Thyroid hormones

23. SECRETION
Levels of some hormones change suddenly in response to certain stimuli
e.g., Epinephrine is released in response to stress or exercise

24. SECRETION Levels of some hormones change in relatively constant cycles
e.g., Reproductive hormones cycle in women during their reproductive years

25. HORMONE TRANSPORT Hormones are dissolved in blood plasma
Transported in two fashions
Free form
Bound to plasma proteins

26. HORMONE TRANSPORT
Free hormones diffuse readily into interstitial spaces
Concentration of hormone in the blood affects the amount of hormone diffusing into interstitial spaces

27. HORMONE TRANSPORT
Many hormones bind only to certain types of plasma proteins
e.g., The type of plasma protein binding to thyroid hormones differs from the type of plasma protein binding to testosterone

28. HORMONE TRANSPORT
Hormones that bind to plasma proteins do so reversibly
H + BP  HBP
This equilibrium is important
Only free hormone can diffuse into the interstitial space
Hormones bound to plasma proteins tend to remain at a relatively constant level in the blood for long periods of time
Decrease in plasma protein concentration reduces half-life of hormone

29. HORMONE TRANSPORT
A decrease in plasma protein concentration reduces the half-life of hormone
Eliminated in either the kidneys of the liver

30. HORMONE TRANSPORT
The circulatory system quickly distributes hormones throughout the body
Diffuse through capillary endothelium
Rate varies between hormones
Lipid-soluble hormones readily diffuse through the walls of all capillaries
Water-soluble hormones pass through pores (“fenestrae”) in the capillary endothelium
Capillary endothelia of organs regulated by protein hormones have large pores
Endocrine glands secreting these hormones also have large pores

31. METABOLISM & EXCRETION
Hormone destruction and elimination limit the time in which they are active
Water-soluble hormones have relatively short half-lives
Rapidly degraded by enzymes
Present in circulatory system or organs
Normally have concentrations that increase and decrease rapidly
Generally regulate activities that have a rapid onset and a short duration

32. METABOLISM & EXCRETION
Hormone destruction and elimination limit the time in which they are active
Lipid-soluble hormones have relatively long half-lives
Commonly circulate in the blood bound to plasma proteins
Reduces rate of elimination
Reduces rate at which they diffuse through capillary endothelium
Normally maintained at relatively constant levels

33. METABOLISM & EXCRETION
Four main modes of hormone removal from the blood
Excretion
Metabolism
Active transport
Conjugation

34. METABOLISM & EXCRETION
Four main modes of hormone removal from the blood
Excretion
Kidneys excrete hormones into the urine
Liver excretes hormones into the bile

35. METABOLISM & EXCRETION
Four main modes of hormone removal from the blood
Metabolism
Hormones metabolized or chemically modified
Enzymes in blood or tissues
e.g., Liver, kidneys, lungs, etc.
End products may be excreted in urine or bile
End products may be taken up by cells
e.g., Epinephrine is modified, then excreted
e.g., Protein hormones are broken down into amino acids
Amino acids are then taken up by cells

36. METABOLISM & EXCRETION
Four main modes of hormone removal from the blood
Active transport
Actively transported into cells
Hormones are recycled
e.g., Epinephrine and norepinephrine are actively transported into cells
These hormones can be secreted again

37. METABOLISM & EXCRETION
Four main modes of hormone removal from the blood
Conjugation
Attachment of water-soluble molecules to hormones
Typically sulfate or glucuronic acid
Increases rate of excretion by kidneys or liver

39. INTERACTION WITH TARGET TISSUES
Intercellular chemical signals
“Ligands”
Bind to proteins and change their functions
Various classes
Hormones
Neurotransmitters
Chemical mediators of inflammation

40. INTERACTION WITH TARGET TISSUES
Ligands bind to proteins at their binding site
Receptor site if protein is a receptor
Lock-and-key fit
“Specificity”
e.g., Insulin binds to insulin receptors
e.g., Insulin does not bind to growth hormone receptors
Multiple types of receptors exist for some hormones
e.g., There are multiple types of epinephrine receptors

41. INTERACTION WITH TARGET TISSUES
Hormones are distributed throughout the body by the circulatory system
Target cells respond to a given hormone
Possess receptors to which the hormone binds
Cells lacking receptors do not respond

42. INTERACTION WITH TARGET TISSUES
Drugs with structures similar to a particular chemical signal may compete with that molecule for their receptor sites
Binding some drugs activates the receptors
Binding of some drugs inhibits the receptor
Blocks binding by the hormone
e.g., RU486 binds to progesterone receptors
Prevents binding by progesterone
Prevents the maintenance of pregnancy

43. INTERACTION WITH TARGET TISSUES
Response to a given concentration of chemical signal
Constant in some cases
Variable in some cases
Two common reasons
Fatigue in the target cells after prolonged stimulation
Number of receptors can decrease after exposure to certain chemical signals
“Down-regulation”
Two mechanisms
Decreased rate of receptor synthesis
Increased rate of receptor degradation

44. INTERACTION WITH TARGET TISSUES
Neurons of the hypothalamus release GnRH
Causes secretion of FSH and LH from the anterior pituitary
Exposure to GnRH causes a reduction in the number of GnRH receptors in cells of the anterior pituitary
Dramatic decrease several hours after exposure
Pituitary becomes less sensitive to GnRH
Normal response of pituitary depends on periodic (not constant) exposure to GnRH

45. INTERACTION WITH TARGET TISSUES
Tissues exhibiting down-regulation of receptors generally respond to short-term increases in hormone concentrations
Tissues responding to relatively constant levels of hormones normally do not exhibit down-regulation

46. INTERACTION WITH TARGET TISSUES
Periodic increases in sensitivity to certain hormones can also occur
“Up-regulation”
Results from an increase in the rate of receptor molecule synthesis
e.g., Increased number of LH receptors in the ovary during each menstrual cycle
FSH from pituitary increases synthesis of LH receptor

48. CLASSES OF RECEPTORS Two main categories of chemical signals
(And two main categories of receptors)
Those binding to membrane-bound receptors
Those binding to intracellular receptors

49. CLASSES OF RECEPTORS
Some chemical signals cannot pass through the plasma membrane
Large molecules and water-soluble molecules
Bind to membrane-bound receptors
Transmembrane receptor proteins
Receptor site exposed on outer surface
Binding of signal to receptor initiates a response inside the cell

50. CLASSES OF RECEPTORS
Some chemical signals readily pass through the plasma membrane
Small and lipid soluble molecules
Bind to intracellular receptors
Hormone-receptor complex may bind to DNA
Alters gene expression
Hormone-receptor complex may bind to enzymes

51. CLASSES OF RECEPTORS Signals binding to membrane-bound receptors
Protein hormones
Glycoprotein hormones
Polypeptides
Some smaller molecules
Epinephrine
Norepinephrine
etc.
Signals binding to intracellular receptors
Thyroid hormones
Steroid hormones
Testosterone
Estrogen
Progesterone
Aldosterone
Cortisol
etc.

52. CLASSES OF RECEPTORS Membrane-bound receptors
Integral membrane proteins
Hormone-receptor binding is reversible
Binding stimulates the intracellular portion of receptor to initiate a response
Three major mechanisms of responses
Altered membrane permeability
Altered activity of G proteins
Altered activity of intracellular enzymes

53. CLASSES OF RECEPTORS Receptors altering membrane permeability
Some receptors comprise part of an ion channel
Ligand-gated ion channels
Binding alters shape of channel
Causes channel to either open or close
Results in a change in the membrane’s permeability to the specific ions passing through the channel

55. CLASSES OF RECEPTORS Receptors activating G proteins G proteins
Bind to receptors at inner surface of plasma membrane
Inactive state binds to GDP

56. CLASSES OF RECEPTORS Receptors activating G proteins
Receptor changes shape upon binding to hormone
GTP replaces GDP on G protein
Alpha subunit separates from other subunits
Alpha subunit can influence ion channels or form intracellular mediators (“second messengers”)

57. CLASSES OF RECEPTORS Receptors activating G proteins
Hormone separates from the receptor
G proteins are no longer activated
Alpha subunits are inactivated as GTP  GDP

58. CLASSES OF RECEPTORS Receptors activating G proteins
Some G proteins activate Ca2+ channels
Ca2+ enters the cell
Can function as an intracellular mediator
Enters or is synthesized inside the cell
Regulates enzyme activities inside the cell

59. CLASSES OF RECEPTORS Receptors activating G proteins
Ca2+ can combine with calmodulin molecules
Calcium-calmodulin complexes activate enzymes
Thee enzymes cause contraction of smooth muscle

60. CLASSES OF RECEPTORS Receptors activating G proteins
Some G proteins alter enzyme activity
Activated alpha subunits can activate the enzyme adenylate cyclase
ATP  cAMP
cAMP binds to kinases
Activated kinases phosphorylate other enzymes
Activity of these enzymes is altered
Either increased or decreased
cAMP is inactivated (cAMP AMP) by the enzyme phosphodiesterase

61. CLASSES OF RECEPTORS
Cyclic AMP acts as an intracellular mediator in many cell types
Enzymes activated are different
Response of each cell type is different
e.g., Glucagon  release of glucose from liver cells
e.g., LH  ovulation

62. CLASSES OF RECEPTORS
The combination of chemical signals with their receptors doesn’t always result in increased cAMP synthesis
Sometimes cAMP synthesis is inhibited by G proteins
There are other common intracellular mediators
e.g., Diacyl glycerol (DAG)
e.g., Inositol triphosphate (IP3)

63. CLASSES OF RECEPTORS
Epinephrine binds to certain receptors in some types of smooth muscle
Binding activates a G protein
Phospholipase C is activated
Phosphoinositol diphosphate (PIP2)  DAG + IP3
DAG activates enzymes that synthesize prostaglandins
Smooth muscle contraction is increased
IP3 releases Ca2+ from the E.R.
Ca2+ enters the cytoplasm and increases smooth muscle contraction

64. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
Intracellular enzymes controlled by the membrane-bound receptors
May be part of the receptor
May be separate molecules

65. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
Effects of altered enzyme activity
Increased or decreased synthesis of intracellular mediator molecules
Phosphorylation of intracellular proteins
Effects of intracellular mediators or phosphorylated proteins
Activation of processes that produce the response of cells to the chemical signals

66. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
Intracellular mediator molecules act as chemical signals
Move from enzymes that produced them into the cytoplasm
Activate processes that produce the response of the cell

67. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
Cyclic guanine monophosphate
cGMP
Intracellular mediator molecule
Synthesized in response to chemical signal binding with a membrane-bound receptor
Produced by the enzyme guanylate cyclase
GTP  cGMP

68. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
Cyclic guanine monophosphate
Combine with and activate specific cytoplasmic enzymes
Activated enzymes produce the response of the cell to the chemical signal

69. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
e.g., ANH binds to receptor in kidney cell membrane
Increased cGMP synthesis
Influences action of enzymes
Stimulates Na+ and H2O excretion
Phosphodiesterase breaks down cGMP
cGMP  GMP
Signal quickly disappears when hormone disappears

70. CLASSES OF RECEPTORS
Some receptors directly alter the activity of intracellular enzymes
Cytoplasmic portion of receptor acts as a phosphorylase enzyme
Phosphorylates several specific proteins
Some are part of the membrane-bound receptor
Others are cytoplasmic
proteins
Phosphorylated proteins influence activity of other cytoplasmic enzymes

71. CLASSES OF RECEPTORS
Many hormones stimulate the synthesis of an intracellular mediator molecule
Often produce rapid responses
Mediator influences already-existing enzymes
Causes a cascade event
Few mediator molecules activate several enzymes
Each activated enzyme activates several other enzymes
Final response is produced

73. CLASSES OF RECEPTORS Intracellular receptors
Present in either the cell’s cytoplasm or nucleus
Lipid-soluble chemical signals
Cross the plasma membrane
Bind to intracellular receptors
Hormone-receptor complex has one of two effects
Alter the activity of cellular enzymes
Bind to DNA and alter the expression of genes

74. CLASSES OF RECEPTORS Receptors binding to DNA
Activate certain specific genes
Transcription of these genes increases
Specific proteins are produced
e.g., Testosterone and estrogen stimulate the production of the proteins responsible for secondary sexual characteristics
e.g., Aldosterone stimulates kidney cells to synthesize proteins increasing the rate of Na+ and K+ transport
Results in increased reabsorption of Na+ and increased K+ secretion

75. CLASSES OF RECEPTORS

76. CLASSES OF RECEPTORS
Cells synthesizing proteins in response to hormonal stimuli normally have a latent period of several hours
Hormones bind, responses are observed