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The Endocrine

System

THE ENDOCRINE SYSTEM

Definition of an endocrine gland

How is this different from an

exocrine gland?

2

Major Endocrine Glands

See Fig. 74-1 See Table 74-1 3

Pituitary

Hypothalamus

Thyroid Parathyroids

Thymus

Adrenals

Pancreas

Ovaries

Testes

Other “Endocrine” Tissues

Pineal gland “biological clock”

Placenta Fetal, breast development

Heart Decreases blood pressure

Increases Na+ excretion by kidneys

Stomach Secretes HCl

Small intestine Secretes of digestive enzymes

Adipose tissue (fat) Large variety of hormones, especially

leptin and adiponectin

See Fig. 74-1 4

Types of Chemical Signals

Endocrine hormones

Secreted by specific cells into the blood; have

specific physiological effects on other body cells

Neurotransmitters

Released by axon terminals; locally acting

Neuroendocrine hormones

Neurotransmitters released into the blood

Paracrine signals

Pass through extracellular spaces to affect

nearby tissues (different cell type)

5

Types of Chemical Signals

Autocrine signals

Secreted into extracellular fluids

Binds to receptors on/in the originating cell

Cytokines

Peptides – mostly related to immune system

Secreted into extracellular fluids

May function as autocrine, paracrine or

endocrine hormones

6

Chemical Structures of Hormones

1) Peptide Hormones

Hydrophilic molecules – pituitary hormones, e.g.

2) Tyrosine-Derived Hormones

E.g., Hormones from thyroid or adrenal medulla

3) Steroid Hormones

Cholesterol derivatives, amphiphilic

E.g., Hormones of gonads and adrenal cortex

7

Hormone Synthesis & Storage: Peptides &

Tyrosine-derived hormones

Preprohormone Prohormone Active hormone

Fig. 74-2 8

Hormone Synthesis & Storage: Steroid

Hormones

Lipid soluble

Steroid passes through cell membranes freely

Implications for synthesis and storage?

9

cholesterol

Fig. 74-3

Which of these is most likely to be stored in

vesicles prior to release?

A) Insulin

B) Estrogen

C) Cortisol

D) Carbon dioxide

10

Which of these is most likely to be reduced in

patients taking a statin drug?

A) Growth hormone

B) Testosterone

C) Thyroxine

D) Nitric oxide

11

Factors Influencing Hormone Production and

Release

Hormones are released in response to

extracellular stimuli:

Hormonal stimuli

Response to other hormones

Humoral stimuli

Response to specific molecules in circulation

Neural stimuli

Response to stress (sympathetic response)

12

Regulation of Hormonal Secretions

Regulation occurs primarily through

feedback mechanisms

Negative feedback

Inhibit stimulus

Direct or indirect

E.g., thyroid hormones

Hypothalamus

TRH

Pituitary

TSH

Thyroid

T3 / T4

x

x

13

Regulation of Hormonal Secretions

Regulation occurs primarily through

feedback mechanisms

Negative feedback

Positive feedback

Reinforce stimulus

E.g., labor contractions

Fetal tissue

stimulus

Uterus / cervix

signal

Hypothalamus

RH

Pituitary

oxytocin 14

Hormone Transport

Water soluble hormones

E.g., peptide & adrenal medullary hormones

Transported in plasma

Short half-life

Cholesterol-based & nonpolar hormones

E.g., steroids, thyroid hormones

Must bind to plasma proteins (i.e., “binding

proteins”) in blood

Longer half-life

15

Angiotensin II is a hormone produced when

blood pressure is low. It causes sodium

retention, water retention, and vasoconstriction,

which all lead to increases in blood pressure.

This is an example of…

A) Positive feedback

B) Negative feedback

C) Feed-forward

16

Cellular Response to Hormones

How are hormones recognized by cells?

What are the general responses of cells to

hormones?

17

Cellular Receptors: Recognition

Peptide hormones

18

Cellular Receptors

Intracellular receptors

19

Cellular Receptors

Notes on receptor specificity…

Receptors are specific to a particular hormone

(with varying degrees of specificity).

A hormone may have multiple types of receptors.

Depending on the receptors present, a single

hormone may elicit varied reactions from

different cells, or from the same type of cell at

different stages of development (fetal vs. adult)

or under different conditions.

20


Change in membrane permeability

Membrane potential changes

E.g., membrane depolarization

Fast action

Ligand-gated ion channels

A.k.a. Ion channel-linked receptors

21


G Protein-Coupled Receptors (GPCRs)

Trimeric G protein binds receptor

G protein activates intracellular signaling

cascade once hormone binds to receptor

Second messenger systems

cAMP

Phospholipase C

22

E.g., cAMP Mechanism of Hormone Action

Fig. 74-7 23

E.g., Phospholipase C Mechanism of Hormone

Action

Fig. 74-8 24


Enzyme-linked receptors

Directly linked

E.g., insulin

Indirectly linked

E.g., leptin

No trimeric G protein

See Fig 74-5 in textbook on Jak-Stat pathway

25


Gene activation

Slow acting

26

Which of these pathways is least likely to

involve gene transcription (and new protein

production?

A) GPCR (via cAMP or PLC)

B) Enzyme-linked receptors

C) Intracellular receptors

D) Nuclear receptors

27

Measurement of Hormone Concentration

Radioimmunoassay

Use specific antibody to detect hormone

Mix radioactive “tracer” hormone, antibody and

sample together

Competitive assay: Tracer competes with

endogenous hormone for Ab binding sites.

The more hormone you have, the less tracer will bind.

Remove all unbound (free) mixture, leaving Ab

bound to either tracer or endogenous hormone

High [endogenous hormone] low tracer

Low [endogenous hormone] high tracer

28


Radioimmunoassay

Measure radioactivity of remaining sample,

compare to standard curve

Fig. 74-9 29


ELISA (enzyme-linked immunosorbent assay)

Coat sample wells with antibody

Add test sample

Add antibody conjugated to enzyme

Add enzyme substrate

Color development

indicates presence

of test substance;

concentration

determined by

comparison to

standard curve

30

Fig. 74-10

What kind of molecule is used as a “molecular

tool” to measure how much of a particular

substance a sample has?

A) Protein

B) Receptor

C) DNA

D) Antibody

31

Survey of Endocrine Tissues

and Hormones

Pituitary Gland

and

Hypothalamus

Cellular Organization

Fig. 75-1

34

Fig. 75-3

Pituitary Control Mechanisms

Neural stimulation by hypothalamus

Negative feedback systems

Direct & indirect mechanisms

Positive feedback systems

35

Hypothalamic Control of Anterior Pituitary

Releasing and inhibiting hormones from

hypothalamus to pituitary

Fig. 75-4 36

Hypothalamic Releasing & Inhibiting Hormones

Examples

Thyrotropin releasing hormone (TRH)

Corticotropin releasing hormone (CRH)

Growth hormone releasing hormone (GHRH)

Growth hormone inhibiting hormone (GHIH)

Aka. somatostatin

Gonadotropin releasing hormone (GnRH)

Prolactin releasing hormone (PRH)

Prolactin inhibiting hormone (PIH)

Aka. dopamine

See Table 75-2 37

The portal circulation carries hormones from

______________ to _____________.

A) Hypothalamus / anterior pituitary

B) Hypothalamus / posterior pituitary

C) Anterior pituitary / hypothalamus

D) Posterior pituitary / hypothalamus

38

Hormones of the Anterior Pituitary

Fig. 75-2 39


Growth Hormone (GH)

Aka. somatotropin (ST)

Regulated by GHRH, GHIH

Protein produced by somatotropes (~30-40% of

cells)

Primary effects

Stimulate cellular growth (protein synthesis,

multiplication, differentiation)

Hypertrophy

Hyperplasia

40


Adrenocorticotropic Hormone (ACTH)

Polypeptide produced by corticotropes

(~20% of cells)

Regulated by CRH

Primary effects

Controls release of adrenocortical

hormones related to:

Electrolyte balance (Na+)

Tissue stress (inflammation)

Metabolism (glucose, protein, fat)

41


Thyroid-stimulating Hormone (TSH)

Aka. thyrotropin

Glycoprotein produced by thyrotropes (~3-5% of

cells)

Regulated by TRH

Primary effects

Stimulates release of thyroid hormones

42


Prolactin (PRL)

Protein produced by lactotropes (~3-5% of cells)

Primary effects

Stimulates lactation & mammary gland

development

Concentration of PRL is correlated with

estrogen levels and controlled by hypothalamus

[estrogen] PRH release (hyp) pituitary PRL

[estrogen] PIH release (hyp) pituitary PRL

43

x


Gonadotropins

Produced by gonadotropes (~3-5% of cells)

Regulated by GnRH

Luteinizing Hormone (LH)

Promotes production of gonadal hormones (e.g.,

testosterone, estrogens, progesterone)

Follicle Stimulating Hormone (FSH)

Stimulates gamete production (oogenesis,

spermatogenesis)

44

Which anterior pituitary hormone is responsible

for maintaining sodium balance?

A) ACTH – adrenocorticotrophic hormone

B) TSH – thyroid stimulating hormone

C) GH – growth hormone

D) FSH – follicle stimulating hormone

45

Growth Hormone

Broad range of effects on cellular metabolism

Atypical for pituitary hormones

General metabolic effects

a.a. uptake & protein synthesis, transcription

protein stability

fat utilization for energy

glucose uptake, insulin secretion

Diabetogenic effect

46

Growth Hormone

Effect of GH injection on body weight in

growing rats

Fig. 75-5

47

Growth Hormone

Effects of exercise and sleep on GH

production

Fig. 75-6

48

Growth Hormone

Factors stimulating GH secretion

Starvation (esp. protein deficiency) – Fig 75-7

Hypoglycemia or hypolipidemia

Exercise

Excitement

Trauma

Ghrelin

Deep sleep

GH secretion drops steadily decreases after

puberty

49

Based on the previous slides, which of these

factors affects GH secretion most strongly on a

daily basis?

A) Sleeping

B) Waking

C) Strenuous exercise

D) Hypoglycemia

50

Growth Hormone

Indirect effects on skeletal system

Stimulates production of insulin-like growth

factors (IGFs; aka somatomedins)

Stimulate bone growth (particularly IGF-I)

Promotes growth in length of long bones

Promotes growth in bone thickness

Congenital defects in IGF-I production causes

dwarfism

Lack bone growth even when given hGH

51

Growth Hormone Abnormalities

Panhypopituitarism

Onset during childhood

Dwarfism

Proportional development but at drastically

reduced rate

Treatable with hGH injections if diagnosed

early

Onset during adulthood

Lethargy, weight gain, loss of sexual function

Due to lack of anterior pituitary hormones

Result of tumor or thrombosis

52


Hypersecretion of GH

Onset during childhood

Gigantism

All body tissues over-

stimulated to grow

Often tumor-related

reverts to

panhypopituitarism due to

tissue destruction

Diabetogenic

53


Hypersecretion of GH

Onset during adulthood

Acromegaly

Growth in bone width

Hands, feet, forehead, jaw, nose, vertebrae

Age 16 Age 52 See Fig. 75-8 54

Overproduction of GH during childhood results

in…

A) Dwarfism

B) Gigantism

C) Acromegaly

D) Panhypopituitarism

55

Hormones of the Posterior Pituitary

Antidiuretic Hormone (ADH)

Aka. (arginine) vasopressin (AVP)

Primary effects

Stimulates kidneys to reabsorb H2O

Oxytocin

Primary effects

Stimulates uterine contractions

+ feedback stimulated by fetus/uterus

Stimulates milk letdown

+ feedback stimulated by suckling

Fig. 75-9

56

ADH

Primarily formed in supraoptic nuclei

Mode of action

Operates under cAMP 2nd messenger system

Increases permeability of distal tubules and

collecting ducts of kidney to H2O to promote

reabsorption

Regulation

Involves osmoreceptors in/near hypothalamus

Specialized cells associated with sensory

neurons that indirectly monitor blood

electrolyte concentrations by sensing cell

distention 57

ADH

H2O

osmosis

[electrolytes]

Y Y cell shrinkage

signal

posterior pituitary

kidneys

ADH

reabsorb H2O [electrolytes] 58

ADH

H2O

osmosis

[electrolytes]

Y Y cell swells

signal

kidneys

ADH H2O not

reabsorbed [electrolytes]

X 59

posterior pituitary

Hypothalamic Control of the Post. Pituitary

Control over the posterior pituitary

See Fig. 75-9 60

True or false: oxytocin is produced and

released by the hypothalamus

A) True

B) False

61

Thyroid

THYROID

Anatomical position

Two lobes lateral to the trachea connected by an

isthmus anterior to the trachea

anterior posterior 63

Primary Hormones of the Thyroid

Thyroid Hormone

Thyroxine (T4) & triiodothyronine (T3)

Tyrosine derivatives

Primary effects

Increase gene transcription to increase cellular

metabolism

CH2O, fat, protein metabolism

BMR ( temp)

Body weight

64

Primary Hormones of the Thyroid

Calcitonin

Release stimulated by humoral [Ca2+]

Primary effects

Inhibits osteoclast activity

Enhances activity of osteoblasts

Promotes Ca2+ uptake / deposition into bone

Deposited as hydroxyapatite crystals

65

Histology of the Thyroid Gland

See Fig. 76-1 66

Thyroid hormones

Calcitonin

Synthesis of Thyroid Hormone

Formation & storage of thyroglobulin (TG)

Glycoprotein containing 70 Tyr residues

Exocytosed into colloid

Fig. 76-2 67


Iodide (I-) trapping & oxidation

Membrane bound I- pump

Concentrates I- to 30x humoral concentration

68 Fig. 76-2


Iodination of TG (organification)

I0 added to Tyr residues of TG

Formation of mono- (MIT; T1) and

diiodotyrosine (DIT; T2) residues

69 Fig. 76-2

Iodination of TG

See Fig. 76-3

70


T1-T2 coupling

Hydrolysis reaction that binds T1 and T2 residues

between adjacent TG molecules

Stored in colloid

71 Fig. 76-2

T1-T2 Coupling

72

See Fig. 76-3


See Fig. 76-3 73


TG uptake

Mature TG endocytosed (pseudopodia)

74 Fig. 76-2


Cleavage & release of T3 / T4

Vesicles fuse with lysosomes

Proteases digest TG and release free T4 (93%)

& T3 (7%)

75 Fig. 76-2

Which of these processes must occur before

the other processes in this list?

A) Iodine organification

B) T1-T2 coupling

C) Thyroglobulin pinocytosis

D) Proteolytic cleavage of TG

E) Synthesis of TG protein

76

Thyroid Hormone Transport & Delivery

Transported in plasma via plasma proteins

Thyroxine-binding globulin

Slow release to tissues

High affinity for plasma proteins (>90% bound)

T4>T3 T4 released to cells slower (6x)

Uptake via diffusion or carriers

Bind nuclear receptors

Initiate/block transcription to increase metabolic

functions

77

Thyroid Hormone Transport & Delivery

Fig. 76-5 78

T3 vs. T4 Activity

T3 more biologically active because…

T4 binds more tightly to plasma proteins

Higher ratio of free:bound T3 vs. T4

T4 converted to T3 within tissues (iodinase)

Nuclear thyroid hormone receptors ~10x greater

affinity for T3

79

Thyroid Hormone Regulation

Stimuli

Thyroid hormone, cold, I-

Control

Negative feedback

Signaling pathways

TRH = phospholipase C

TSH = cAMP

Stimulates all known

secretory functions of thyroid

TSH T3/T4 release in 30

min

Hypothalamus

TRH

Pituitary

TSH

Thyroid

T3 / T4

80

TSH

Increases TG proteolysis

Increases iodide pump activity

Increases organification (iodination) activity

Increases size / activity of thyroid cells

Increases number of thyroid cells

81

Increases or decreases in TRH causing

increases or decreases in TSH level is an

example of…

A) Hormonal regulation of TSH

B) Hormonal regulation of TRH

C) Negative feedback

D) Positive feedback

82

Physiological Effects of Thyroid Hormone

Effects on cellular metabolism

Macromolecules

all aspects of (CH2O)n metabolism

Uptake

Glycolysis

Gluconeogenesis

lipid mobilization and oxidation to free fatty

acids

cholesterol & triglycerides in plasma

cholesterol excretion in bile

83

Effect on Basal Metabolic Rate (BMR)

Slow onset, long duration

[high] increases BMR 60-100%

[low] decreases BMR 30-50%

84

Effect of Large Single Dose on BMR

Fig. 76-4

85

Long latent period; prolonged effect

Daily Effect on BMR

Fig. 76-6 86

“norm”


Effect on body weight

[increase] weight decrease

However, may be offset by increased appetite

[decrease] weight increase

Effect on cardiovascular system

Increased…

Heart rate, blood pressure, cardiac output

Inotropy (contractility/strength of contraction)

87


Effect on respiratory system

Increased…

Breathing rate and depth

Effect on nervous system

[increase] irritability & nervousness

[decrease] depression, lethargy

88

Based on the previous slides, which of these is

most likely to be a symptom associated with

hyperthyroidism?

A) Lethargy / fatigue

B) Slow reaction time

C) Weight loss

D) Reduced cardiac output

89

Hyperthyroidism

General symptoms

Excitability / nervousness

Intolerance to heat / profuse sweating

Weight loss

Fatigue / insomnia

Exophthalmos

Protrusion of the eyeballs due to edema of

orbital tissues

See Fig. 76-8 90

Hyperthyroidism

Graves disease

Autoimmune disease

Ab bind TSH receptors on thyroid

Results in continual hormone secretion

Symptoms

Exophthalmos

Goiter

Other typical symptoms

91

Hyperthyroidism

Treatment

Typically tumor related

Surgery

Radiation treatment (131I)

Why use this isotope?

92

Hypothyroidism

General Symptoms

Fatigue

Mental sluggishness

Weight gain

Myxedema

General edema

Fig. 76-9 93

Hypothyroidism

Endemic goiter

Caused by dietary iodine deficiency

Thyroid stimulated to produce thyroid hormone

but is unable to produce active hormone

Follicle cells replicate; follicles swell (10-20x)

May return to normal with dietary iodine

supplements

iodized salt

94

Hypothyroidism

Cretinism

Severe hypothyroidism during fetal stages /

infancy / childhood

Symptoms

Mental retardation

Short / disproportionate body

Thick tongue / neck

Treatable with hormone replacement therapy but

symptoms irreversible

95

Hypothyroidism

Hashimoto Thyroiditis

Hypothyroidism due to autoimmune attack

against thyroid peroxidase or thyroglobulin

Most common form of primary hypothyroidism

in North America

Symptoms same as other adult forms of

hypothyroidism

Treatable with hormone replacement therapy

(T4)

Which of these diseases is a type of

hypothyroidism that is due to an autoimmune

cause?

A) Hashimoto thyroiditis

B) Grave’s disease

C) Endemic goiter

97

Parathyroid Glands

PARATHYROID GLANDS

Anatomy

Typically 2 pairs on posterior surface of thyroid

lobes

99

Parathyroid Hormones

Parathyroid hormone (PTH)

Elevates blood calcium levels

10

0

Vitamin D Conversion

Fig. 79-6 101

Physiological Roles of Ca2+

Critical component in nerve transmission

Neurotransmitter release

Critical component in muscle contraction

Exposure of myosin binding sites on actin

filaments

Autorhythmic cycles of cardiac muscle

Exocytosis

Intracellular signaling

Homeostasis maintained by antagonistic

effects of PTH and calcitonin 102

Parathyroid hormones has all of the following

effects EXCEPT:

A) Stimulating osteoclast activity

B) Inhibiting osteoblast activity

C) Increasing intestinal absorption of Ca2+ directly

D) Stimulating the kidney to produce more

vitamin D

103

Adrenal Glands

ADRENAL GLANDS

Anatomical considerations

Located on superior surface of kidneys (humans)

Cortex vs. medulla

See Fig. 77-1 105

Cortex vs. Medulla

Functional differences

Adrenal cortex: produces corticosteroids

Cholesterol derivatives

Examples: aldosterone, cortisol, sex steroids

Adrenal medulla: produces catcholamines

Produce catecholamines

Examples: epinephrine & norepinephrine

106

Hormones of the Adrenal Cortex

3 primary hormone groups produced by

the 3 primary cell layers

Zona glomerulosa

Produce mineralocorticoids

E.g., aldosterone

107




Zona glomerulosa

Zona fasciculata

Produce glucocorticoids &

some gonadocorticoids

108




Zona glomerulosa

Zona fasciculata

Zona reticularis

Produce gonadocorticoids &

some glucocorticoids

109

Hormones of the

Adrenal Cortex

Fig. 77-2

Synthesis

pathways

110

The primary hormone produced by the zona

glomerulosa of the adrenal cortex is…

A) Aldosterone

B) Cortisol

C) Adrenal androgens

D) All of the above

111

Mineralocorticoids

Aldosterone

Primary effects

Regulation of [electrolyte] in extracellular

fluids

Na+, K+

Primary target = kidneys

Stimulates reabsorption of Na+ from urine

Na+ in plasma water follows blood

volume & blood pressure

Stimulates K+ excretion in urine

Critical for survival

112

Effects of Na+ / K+ Imbalances

Sodium

Excess/deficiency of Na+ in plasma

Osmotic imbalance Δ blood volume &

pressure

Excess Na+ in urine

Water follows blood volume & bp

circulatory shock

Potassium

Excess K+ in plasma

Hypertension, heart failure

K+ deficiency in plasma

Inhibits muscle/nerve depolarization 113

Effect of Aldosterone Infusion

sodium

retention…

arterial

pressure

extracellular

fluid

urinary Na+

output

“escape” due

to filtration

pressure

Fig. 77-3

114

Aldosterone Regulation

ACTH

Required for aldosterone secretion

Does not influence rate of secretion

K+ concentration

[K+ ] stimulates zona glomerulosa cells

Aldosterone release

Na+ concentration

[Na+ ] only slightly inhibits aldosterone release

115

Aldosterone Regulation

Renin-angiotensin

system

Cells in kidneys

stimulated by…

blood pressure,

blood volume,

plasma

osmolarity

Fig. 19-9

116

Glucocorticoids

Cortisol (hydrocortisone) & cortisone

Primary effects

Increase blood glucose

Increase gluconeogenesis

Synthesis of glucose from amino acids

Depress inflammation & immune response

Inflammatory reaction may

overcompensate for actual problem

Increase “healing” through energy

availability and mobilization of precursors

for structural components (aa’s, fa’s)

117

Regulation

Fig. 77-6

Fig. 77-7

118

Gonadocorticoids

Adrenal androgens

Sex hormones

Primarily “male” hormones

Testosterone precursor, androstenedione

Can be converted to estrogens

Also progesterone and estrogens

All secreted in small amounts with weak effects

relative to hormones of gonad origin …so why do we care about this?

119

Hypoadrenalism

Addison’s disease

Typically autoimmune reaction resulting in

atrophy of cortex

Mineralocorticoid & glucocorticoid deficiencies (why not adrenal androgens, too?)

Dehydration ( aldosterone)

Hypertension ( K+)

Blood glucose imbalance ( glucocorticoids)

120

Hyperadrenalism

Cushing’s syndrome

Primarily due to cortisol excess (due to ACTH

excess)

Hypertension & edema

Facial edema (“moon face”) & acne

Redistribution of fat

Abdomen & posterior neck (buffalo hump)

Protein loss

Weakness

Depressed immunity

Fig. 77-9 121

Which disease is most likely the result of an

autoimmune destruction of the adrenal cortex?

A) Cushing disease

B) Addison’s disease

C) PCOS

D) All of the above

122

Hormones of the Adrenal Medulla

Catecholamines

Epinephrine (adrenaline)

Norepinephrine (noradrenaline)

General effects

Emergency response (fast / brief)

heart rate, metabolic rate, blood

pressure (vasoconstriction)

Same results; epinephrine provides stronger

response

Short term response

123

See p. 751

Hormones of the Adrenal Medulla

Stimulus

Sympathetic NS response (fight / flight)

Signals adrenal medulla

Catecholamines released

Epinephrine (80%)

Norepinephrine (20%)

124

Which hormone is released in the largest

quantities by the adrenal medulla?

A) Aldosterone

B) Cortisol

C) Epinephrine

D) Norepinephrine

125

Pancreas

PANCREAS

Cellular composition Mixed gland

Endocrine & exocrine activity

Islets of Langerhans

cells (60%)

Insulin

cells (25%)

Glucagon

cells (10%)

Somatostatin (GHIH)

Fig. 78-1

127

Endocrine Activity of the Pancreas

Regulate blood glucose levels

Uptake / release of glucose

Fat & protein metabolism

Conditions of imbalance:

Hyperglycemia

Hypoglycemia

128

In cells: insulin production

Released in response to elevated blood glucose

Fig. 78-7 129

Insulin Processing

Fig. 78-2 130

C-Peptide

A-chain

B-chain

S S

S S

S S

S S

S S

S S

Connecting peptide

Insulin

HOOC

NH2

NH2

NH2

COOH

COOH

Proinsulin

A-chain B-chain

1

5

10 15

20

25

30

1 5 10 15

20

1 5 10 15 20 25 30

1

5 10

15

20

In target cells: Insulin signaling

Membrane receptors consist of 4 subunits

Fig. 78-3

131

If you didn’t already know that insulin is a

protein, you could assume that it is based on

the fact that…

A) it reduces blood glucose levels

B) it is released from the pancreas

C) it is released in response to increases in

intracellular calcium

D) it binds to receptors on the plasma membrane

of target cells

132

Insulin

Release produces a hypoglycemic effect

Glucose uptake

Esp., muscle, liver, adipose

Fig. 78-8

133

Fig. 78-9 Fig. 78-4

Insulin

Effect on glucose storage

[Glycogen] in liver

Convert glucose to triglycerides

Effect on fuel utilization

Increased a.a. transport

Increased mRNA translation

Inhibition of protein catabolism

Depressed gluconeogenesis (liver)

Depressed fat utilization & increased storage

(“fat sparer”)

134

Insulin

Effect on nervous tissue

Essentially none

Neurons very “permeable” to glucose, don’t

require insulin for glucose uptake

Normally use only glucose as energy source

135

Insulin

Synergistic effect with growth hormone

Fig. 78-6

136

Glucagon

Released in response to decreased blood

glucose

Release provides hyperglycemic effect

Glycogen breakdown & release

Liver glycogen

Muscle glycogen

Enhances gluconeogenesis

Glucose production from amino acids

Activates adipose cell lipase

Release fatty acids for energy use

137

Factors Affecting Insulin / Glucagon Release

See Table 78-1

Figs. 78-9, 78-10 138

General Regulation

139

Other Regulatory Factors

Increased aa levels enhance effect of

glucose on insulin release

Gastrointestinal hormones increase insulin

secretion

E.g., gastrin, cholecystokinin (CCK)

Severe hypoglycemia

Hypothalamus stimulates sympathetic response

Epinephrine stimulates glucose release from

liver

Release of growth hormone and cortisol

Inhibit glucose utilization; increase fat

utilization 140

Insulin levels are increased by all of the

following except:

A) hyperglycemia

B) Severe hypoglycemia

C) Normal hypoglycemia

D) CCK

141

Diabetes Mellitus

Physiological effects of hyperglycemia

Glucose in urine (glycosuria)

Dehydration

Increased diuresis (polyuria)

Excessive thirst (polydipsia)

Hunger (polyphagia) with weight loss

Ketoacidosis (not an effect; coincidental, resulting from low insulin

levels)

Shift to fat metabolism for energy fatty

acids in blood

Acetone breath

Rapid/deep breathing (CO2 buffering)

Diabetic (acidotic) coma (blood pH <7.0) 142

Diabetes Mellitus

Type I diabetes (insulin-dependent)

Cause

Lack of insulin secretion

Predisposing factors

Heredity

Autoimmune reaction (viral related)

Early onset (< 20 yrs)

Treatment

Insulin

143

Diabetes Mellitus

Type II diabetes (non-insulin-dependent) Cause

Decreased cellular sensitivity to insulin (insulin resistance)

Predisposing factors Heredity Obesity (reduction in transport proteins)

Traditionally late onset (>40 yrs), now earlier Treatment

Diet & exercise Insulin Drugs

Increase tissue insulin sensitivity (thiazolidinediones, metformin)

Increase insulin production/release (sulfonylureas)

144

Diabetes Mellitus

Testing

Acetone breath

Urinary glucose

Fasting blood glucose levels

Morning blood glucose should be

~90mg/100ml

145

Diabetes Testing

Glucose tolerance test

Evaluate glucose clearance rate

Ingest 1g glucose/kg body weight

Blood glucose returns to normal within 2 hr

With diabetes…

Much greater rise in blood glucose

Delay in return to normal levels

To determine Type I or Type II…

Test insulin levels

146

Glucose Tolerance Test

Fig. 78-12

147

Hypoglycemia

Not enough glucose available for nervous

tissue

General symptoms

Nervousness

Trembling

Sweating

Seizure

Unconsciousness

Coma

Death

glucose 50-70mg/100ml

glucose 20-50mg/100ml

148

True or false: Type II diabetes only occurs in

people over 40

A) true

B) false

149

Gonads

GONADS

Testes Androgens

Testosterone,

dihydrotestosterone,

androstenedione

Conversion to estrogen

(estradiol) in other

tissues

Ovaries Estrogens,

progesterone

Hypothalamus

GnRH

Pituitary

LH

FSH

Gonads Fig. 81-6

Fig. 80-8

151

Testosterone

Fetal development Responsible for initial development of male

sexual organs from genital ridge

Produced 7th week of development → 10 weeks after birth

Not produced again until 10-13 yrs

Fig. 80-9 152

Testosterone

Puberty - adult

Development of primary & secondary sexual

characteristics

Hair distribution and baldness

Increased skin thickness & rate of sebaceous

gland secretion ( acne)

Increased muscle mass and bone thickness

Increased BMR

Spermatogenesis

153

True or false: “Manopause” is when men stop

producing testosterone when they get to ~65

years old

A) true

B) false

154

Estrogens

Promote development of most secondary

sex characteristics; progression of

endometrial cycle

Forms

Estradiol (-estradiol)

Primary product; most potent

Estrone

Also formed from adrenal

androgens

Estriol

Derivative of estradiol & estrone

Conversion mainly in liver

Fig. 81-6

155

Estrogens

Only minute quantities secreted during

childhood

Production decreases at menopause

Fig. 81-10 156

Estrogens

Development of primary & secondary sexual

characteristics

Increased osteoblast activity

Uniting of the epiphyses

Decreased osteoblast activity after menopause

Osteoporosis

Increases fat deposition (sc / gluteofemoral)

Thickening, softening of skin

Increased vascularization

157

Progestins

Preparation of …

Uterus for pregnancy

Breasts for lactation

Progression of endometrial cycle

Primary form

Progesterone

Secreted by corpus luteum during latter half of

ovarian cycle

Secreted by placenta during pregnancy

158

Endometrial Cycle

Proliferative phase

Proliferation of epithelial cells and development

of uterine endometrial layer after menstruation

Influenced by elevated estrogen levels

159

Endometrial Cycle

Secretory phase

Increased secretion of estrogens and

progesterone after ovulation

Increased development of the endometrium

Secretory activity relates to nutrient storage

for implanted fertilized ovum (uterine milk)

160

Endometrial Cycle

Menstruation

Sloughing of endometrium

Reduction in estrogens and progesterone (10)

161

Endometrial Cycle

Fig. 81-7

Fig. 81-3 162

Which hormone is primarily responsible for

driving the uterine cycle (menstrual cycle)?

A) -estradiol

B) Progesterone

C) Testosterone

D) Cortisol

163

the endocrine system - warner pacific universityclasspages.warnerpacific.edu/bdupriest/bio 420/unit...

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