1. The Endocrine System
Chapter 46

2. Types of Chemical Messengers
A hormone is a chemical that is secreted into extracellular fluid and carried by the blood
-Can therefore act at a distance from source
-Only targets with receptor can respond
Paracrine regulators do not travel in blood
-Allow cells of organ to regulate each other
Pheromones are chemicals released into the environment to communicate among individuals of a single species

3. Types of Chemical Messengers
Some neurotransmitters are distributed by the blood and act as neurohormones
-Norepinephrine coordinates the activity of heart, liver and blood vessels during stress
Hormone production and release is often regulated directly or indirectly by the nervous system

4. Hormones carried by blood
Axon
Neurotransmitters
Glands
Paracrine secretion
Hormones
carried by blood
Target cell
Extracellular
space
Receptor
proteins
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5. Endocrine System
The endocrine system includes all the organs and tissues that produce hormones
-Includes endocrine glands, which are specialized to secrete hormones
-Also organs, like the liver, that secrete hormones in addition to other functions
Exocrine glands secrete their products, such as saliva or milk, into a duct for transport to the outside

6. Parathyroid glands (behind thyroid)
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Ovaries (in females)
Parathyroid glands
(behind thyroid)
Hypothalamus
Pineal gland
Neurohypophysis
Pituitary
gland
Thyroid gland
Thymus
Adrenal
glands
Pancreas
Testes
(in males)
Adenohypophysis

7. Classes of Hormones
Molecules that function as hormones must exhibit two basic characteristics
1. Must be sufficiently complex to convey regulatory information to their target cells
2. Must be adequately stable to resist destruction before reaching their target cells
Three chemical classes meet these requirements

8. Classes of Hormones 1. Peptides and proteins -Glycoproteins
2. Amino acid derivatives
-Catecholamines
-Thyroid hormones
-Melatonin
3. Steroids
-Sex steroids
-Corticosteroids

9. Classes of Hormones Hormones may be categorized as:
-Lipophilic (nonpolar) = fat-soluble
-Steroid hormones and thyroid hormones
-Bind to intracellular receptors
-Hydrophilic (polar) = water-soluble
-All other hormones
-Bind to extracellular receptors

10. Lipophilic Hydrophilic 1. Hormones 2. Hormones 3. Nontarget5 3 4 1 2
Lipophilic
Hydrophilic
Endocrine gland A
Endocrine gland B
1. Hormones
secreted into
extracellular
fluid and
diffuse into
2. Hormones
distributed by
blood to all cells.
Diffuse from blood
to extracellular
fluid.
3. Nontarget
cells lack
receptors,
and cell
stimulation does
not occur.
4. Target cells
possess
receptors, and are
activated by
hormones.
5. Unused,
deactivated
hormones are
removed by the
liver and kidney.
Secretory
vesicles
Hormones
Transport proteins
Membrane
receptors
Target cell
Activated
Nuclear
receptor
Nontarget
cells
Extracellular
fluid
Blood
vessels
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11. Paracrine Regulators Paracrine regulation occurs in most organs
-Growth factors are proteins that promote growth and cell division in specific organs
-Epidermal growth factor = Skin
-Nerve growth factor = Neurons
-Insulin-like growth factor = Bone
-Cytokines = Immune system

12. Paracrine Regulators
The endothelium of blood vessels is a rich source of paracrine regulators
-Nitric oxide (NO) which promotes vasodilation
-Endothelin which stimulates vasoconstriction
-Bradykinin which promotes vasodilation

13. Paracrine Regulators Prostaglandins
-A diverse group of fatty acids that are produced in almost every organ
-Regulate a variety of functions including:
-Smooth muscle contraction, lung function, labor, and inflammation
-Synthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen

14. Lipophilic Hormones
Lipophilic hormones include the steroid hormones (derived from cholesterol) and the thyroid hormones (tyrosine + iodine)
-As well as the retinoids, or vitamin A
Thyroxine
Cortisol (Hydrocortisone) O HO OH
H3C
CH2OH C I
NH2
CH2
COOH
Testosterone CH

15. Lipophilic Hormones
These hormones circulate in the blood bound to transport proteins
-Dissociate from carrier at target cells
-Pass through the cell membrane and bind to an intracellular receptor, either in the cytoplasm or the nucleus
-Hormone-receptor complex binds to hormone response elements in DNA
-Regulate gene expression

16. 1. Hormone passes 2. Inside target 3. Hormone-receptor
Blood
plasma
Protein
Lipophilic hormones
mRNA
DNA
Hormone response element
1. Hormone passes
through plasma
membrane
2. Inside target
cell the hormone
binds to a
receptor protein
in the cytoplasm
or nucleus
3. Hormone-receptor
complex binds to
hormone response
element on DNA,
regulating gene
transcription
4. Protein synthesis
5. Change in protein
synthesis is
cellular response
Cytoplasm
Plasma membrane
Nucleus
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17. Hydrophilic Hormones
Hydrophilic hormones include the peptide, protein and catecholamine hormones
-Too large or polar to cross cell membrane
Hormones bind to extracellular receptors
-Initiate signal transduction pathways
1. Activation of protein kinases
2. Production of second messengers

18. 1. Receptors Function as Kinase Enzymes
Hormone
Inactive
Active kinase
domain
Receptor
Target
protein P
Phosphorylated
GPCR
Inactive G
Active G
Second messenger-
generating enzyme
Hormones
GTP
GDP
protein kinase
proteins
Active
Protein
kinase
Second
messenger
1. Receptors Function as Kinase Enzymes
2. Receptors Activate G Proteins
Cellular
response g a b
ADP
ATP
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19. Hydrophilic Hormones Receptor kinases
-For some peptide hormones (like insulin) the receptor itself is a kinase
-Can directly phosphorylate intracellular proteins that alter cellular activity
-For other peptide hormones (like growth hormone) the receptor itself is not a kinase
-Rather, it activates intracellular kinases

20. Hydrophilic Hormones Second-messenger systems
-Many hydrophilic hormones work through second messenger systems
-Two have been described:
-One involving cyclic adenosine monophosphate (cAMP)
-One that generates 2 lipid messengers: inositol triphosphate (IP3) and diacyl glycerol (DAG)

21. Hydrophilic Hormones Second-messenger systems
-Receptors are linked to a second-messenger-generating enzyme via membrane proteins called G proteins
-Are thus called G-protein-coupled receptors (GPCP)
-When the G protein activates the enzyme, the second-messenger molecules increase

22. The Pituitary Gland
The pituitary gland is also known as the hypophysis
-It hangs by a stalk from the hypothalamus
The pituitary gland consists of two parts:
-Anterior pituitary (adenohypophysis)
-Appears glandular
-Posterior pituitary (neurohypophysis)
-Appears fibrous

23. The Posterior Pituitary
The posterior pituitary develops from growth of the brain
-It remains directly connected to the hypothalamus by a tract of axons
It stores and releases two hormones, that are actually produced by neuron cell bodies in the hypothalamus
-Neuroendocrine reflex

24. The Posterior Pituitary
Antidiuretic hormone (ADH)
-A peptide hormone that stimulates water reabsorption by the kidney, and thus inhibits diuresis (urine production)
Oxytocin
-Like ADH, it is composed of 9 amino acids
-In mammals, it stimulates the milk ejection reflex and uterine contractions during labor, and it regulates reproductive behavior

25. ADH increases vasoconstriction ADH reduces urine volume Effector
ADH synthesized
by neurosecretory
cells in the
hypothalamus
is released
from neuro-
hypophysis into
blood
Integrating Center
Water returned to
Response
Increases
blood pressure
Osmotic
concentration of
blood increases
Stimulus
Dehydration
Lowers blood
volume and
pressure
Osmoreceptors
in CNS monitor
concentration
Sensor
Baroreceptors
in aorta
monitor pressure
( – )
Negative
feedback
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26. The Anterior Pituitary
The anterior pituitary develops from a pouch of epithelial tissue of the embryo’s mouth
It produces at least seven essential hormones
-Collectively called tropic hormones or tropins
-Can be categorized into three families
-Peptide hormones, protein hormones and glycoprotein hormones

27. The Anterior Pituitary
Peptide hormones
-Fewer than 40 amino acids in size
-Adrenocorticotropic hormone (ACTH)
-Melanocyte-stimulating hormone (MSH)
Protein hormones
-A single chain of about 200 amino acid
-Growth hormone (GH)
-Prolactin (PRL)

28. The Anterior Pituitary
Glycoprotein hormones
-Dimers, containing alpha (a) and beta (b) subunits, each around 100 amino acids
-Thyroid-stimulating hormone (TSH)
-Luteinizing hormone (LH)
-Follicle-stimulating hormone (FSH)

29. The Anterior Pituitary
The activity of the anterior pituitary is controlled by hormones of the hypothalamus
-Neurons secrete releasing hormones and inhibiting hormones, which diffuse into blood capillaries at the hypothalamus’ base
-Each hormone delivered by the hypothalamohypophysial portal system regulates a specific anterior pituitary hormone

30. Secondary capillaries Neurohypophysis Primary capillaries
Portal veins
Hypothalamus
Adenohypophysis
Secondary capillaries
Neurohypophysis
Primary capillaries
Primary
capillaries
Axons to primary
Neuron cell
bodies
Hormones
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31. The Anterior Pituitary
The hypothalamus and the anterior pituitary are partially controlled by the very hormones whose secretion they stimulate
-This is termed negative feedback or feedback inhibition
Positive feedback is uncommon because it causes deviations from homeostasis
-One example is the control of ovulation

32. Hypothalamus Adenohypophysis Target Glands Hormones Releasing hormones
Tropic hormones
(TSH, ACTH, FSH, LH)
Adenohypophysis
Thyroid, adrenal
cortex, gonads
Target Glands
Hormones
Releasing hormones
(TRH, CRH, GnRH)
Hypothalamus
( + )
Target
cells
( – )
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Negative
feedback

33. The Anterior Pituitary
The anterior pituitary is sometimes referred to as the “master gland”
-Its effects may be direct or indirect
-Direct: activation of nonendocrine targets
-Indirect: activation of other endocrine glands
Hypophysectomy is the surgical removal of the pituitary

34. Anterior Pituitary Disorders
Growth hormone stimulates growth of muscles and connective tissue
-It also promotes the production of insulin-like growth factors
-Stimulate cell division in the epiphyseal growth plates, and thus bone elongation
Gigantism is caused by an excessive secretion of growth hormone in a child

35. Anterior Pituitary Disorders

36. Anterior Pituitary Disorders
In contrast, pituitary dwarfism is caused by a deficiency in GH secretion during childhood
GH can no longer cause an increase in height in adults because human skeletal plates transform from cartilage into bone at puberty
-Excessive GH secretion in an adult results in acromegaly

37. The Thyroid Gland
In humans, the thyroid gland is shaped like a bow tie, and lies just below the Adam’s apple in the front of the neck
-It secretes:
-Thyroid hormones
-Thyroxine
-Triiodothyronine
-Calcitonin

38. The Thyroid Gland Thyroid hormones bind to nuclear receptors
-Regulate carbohydrate & lipid metabolism
-Adults with hypothyroidism have low production of thyroxine
-Reduced metabolism and overweight
-Adults with hyperthyroidism have high production of thyroxine
-High metabolism and weight loss
-Trigger metamorphosis in amphibians

39. rapid differentiation
Thyroxine production
–35
–30
–25
–20
–15
Days from emergence of forelimb
–10 –5 +5
+10
+20
TSH stimulates thyroid to produce
thyroxine.
Forelimbs emerge. T
ail is reabsorbed .
Hypothalamus
stimulates
adenohypophysis to
secrete TSH.
Rapid growth
Reduced growth,
rapid differentiation
Rapid differentiation
Premetamorphosis
Prometamorphosis
Climax
Receptor stimulation
Hypothalamus stimulation
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40. The Thyroid Gland Calcitonin -A peptide hormone
-Stimulates the uptake of calcium (Ca2+) into bones
-Thus, lowering its levels in the blood

41. The Parathyroid Glands
The parathyroid glands are four small glands attached to the thyroid
-Produce parathyroid hormone (PTH) in response to falling levels of Ca2+ in blood
-Stimulates osteoclasts to dissolve calcium phosphate crystals in the bone matrix and release Ca2+ into blood
-Stimulates the kidneys to reabsorb Ca2+ from the urine

42. The Parathyroid Glands
PTH also indirectly leads to the absorption of Ca2+ from food in the intestines by its activation of vitamin D
-Vitamin D is produced in the skin from a cholesterol derivative in response to UV light
-It diffuses into blood in an inactive form
-Activated by an enzyme that is stimulated by PTH

43. Stimulus Parathyroid Effector Response Increased blood Ca2+
Low blood Ca2+
Stimulus
Parathyroid glands
Parathyroid
Secretes
PTH
( + )
( – )
Osteoclasts
dissolve Ca(PO4)2
crystals in bone,
releasing Ca2+
Effector
Reabsorption of
Ca2+, excretion
of PO43–
absorption of Ca2+
from intestine (due
to PTH activation
of vitamin D)
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Negative feedback

44. The Adrenal Glands
The adrenal glands are located just above each kidney
-Medulla = Inner portion
-Stimulated by the sympathetic division of the autonomous nervous system
-Cortex = Outer portion
-Stimulated by the anterior pituitary, through the hormone ACTH

45. The Adrenal Glands
The medulla secretes the catecholamines epinephrine and norepinephrine
-These trigger “alarm” responses helping the body prepare for extreme efforts
-Lead to an increase in: heart rate, blood pressure, blood glucose level, and blood flow to heart and muscle

46. The Adrenal Glands
The cortex secretes steroid hormones called corticosteroids
-Glucocorticoids (such as cortisol) maintain glucose homeostasis and modulate some aspects of the immune response
-Mineralocorticoids (such as aldosterone) regulate mineral balance by stimulating the kidneys to reabsorb Na+ and excrete K+

47. Catecholamine Hormones Glucocorticoids Stimulus
Sympathetic nervous
system
Sympathetic
axons
Adrenal medulla
Adrenal cortex
Adenohypophysis
Effector
Catecholamine Hormones
Glucocorticoids
ACTH secreted from
the adenohypophysis
Longer term stress
response.
( + )
Stress
Stimulus
( – )
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Effects on lipid and
carbohydrate metabol-
ism, immune system,
and damage repair.
Short term stress
Effects on cardiovascular
system, carbohydrate and
lipid metabolism, central
nervous system.
Negative
feedback

48. The Pancreas The pancreas is located adjacent to stomach
-Connected to the duodenum of the small intestine by the pancreatic duct
The islets of Langerhans are scattered clusters of cells throughout the pancreas
-These govern blood glucose levels through two hormones with antagonistic functions

49. The Pancreas Insulin -Secreted by beta (b) cells of the islets
-Stimulates cellular uptake of blood glucose and its storage as glycogen in the liver and muscle cells or as fat in fat cells
Glucagon
-Secreted by alpha (a) cells of the islets
-Promotes the hydrolysis of glycogen in the liver and fat in adipose tissue

50. Stimulus After a Meal Between Meals Effector Response ( + ) ( – )
Blood glucose increased
Stimulus
Blood glucose decreased
After a Meal
Between Meals
Effector
Increased glucagon
production
by a cells
Increased insulin
by b cells
Response
Glycogen hydrolyzed to
glucose, then secreted into
blood, increasing blood glucose
Glucose moves from
blood into cells,
reducing blood glucose
Sensor
Pancreatic
Islets
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Negative Feedback

51. Diabetes Mellitus Diabetics cannot take up glucose from blood
-Type I (insulin-dependent diabetes)
-Individuals lack insulin-secreting b cells
-Treated by daily injections of insulin
-Type II (noninsulin-dependent diabetes)
-Most patients have this form
-Very low number of insulin receptors
-Treated by diet and exercise

52. The Gonads The ovaries and testes in vertebrates
-Produce sex steroids that regulate reproductive development
-Estrogen and progesterone
-“Female” hormones
-Androgens
-“Male” hormones
-Testosterone and its derivatives

53. The Pineal Gland
The pineal gland is located in the roof of the third ventricle of the brain
-Functions as an endocrine gland by secreting the hormone melatonin
-Reduces dispersal of melanin granules
-Regulates biological clocks
-Synchronizes various body processes to a circadian rhythm

54. Other Hormones
Some hormones are secreted by organs that are not exclusively endocrine glands
-Atrial natriuretic hormone is secreted by the right atrium of the heart
-Promotes salt and water excretion
-Erythropoietin is secreted by the kidney
-Stimulates the bone marrow to produce red blood cells

55. Insect Hormones
Insects undergo two types of transformations during post-embryonic development
-Molting = Shedding of old exoskeleton and secretion of a new larger one
-Metamorphosis = Radical transformation from the larval to the adult form

56. Insect Hormones
Hormonal secretions influence both molting and metamorphosis
-Brain hormone stimulates prothoracic gland to produce ecdysone, or molting hormone
-High levels cause molting
-The corpora allata produce a hormone called the juvenile hormone
-Low levels result in metamorphosis

57. Neurosecretory cells Larval molt Pupal molt Adult molt Corpora allata
Prothoracic
gland
Brain hormone
Juvenile hormone
Ecdysone
Low
amounts
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