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

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

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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

Axon

Neurotransmitters

Glands

Paracrine secretion

Hormonescarried by blood

Target cell

Extracellularspace

Receptorproteins

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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


Ovaries (in females)

Parathyroid glands(behind thyroid)

Hypothalamus Pineal gland

NeurohypophysisPituitarygland

Thyroid gland

Thymus

Adrenalglands

Pancreas

Testes(in males)

Adenohypophysis

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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

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Classes of Hormones

1. Peptides and proteins-Glycoproteins

2. Amino acid derivatives-Catecholamines-Thyroid hormones-Melatonin

3. Steroids-Sex steroids-Corticosteroids

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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

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33

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1 1

2

LipophilicHydrophilic

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.

Secretoryvesicles Hormones

Hormones

Transport proteins

Membranereceptors

Target cell Target cell

ActivatedActivated

Nuclearreceptor

Nontargetcells

Nontargetcells

Extracellularfluid

Extracellularfluid

Bloodvessels


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

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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


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

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Lipophilic Hormones

Lipophilic hormones include the steroid hormones (derived from cholesterol) and the thyroid hormones (tyrosine + iodine)

-As well as the retinoids, or vitamin AThyroxineCortisol (Hydrocortisone)

O

HO OHH3C

CH2OH

C O

HO O

I I

I I NH2

CH2

COOH

H3C

Testosterone

O

OH

H3C

H3C

CH

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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

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Receptor

Bloodplasma

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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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

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Hormone

InactiveActive kinasedomain

Receptor

Targetprotein

P

P P P

Phosphorylatedprotein

GPCR

Inactive Gprotein

Active Gprotein

Second messenger-generating enzyme

Hormones

GTPGTPGDP

GPCR

Inactiveprotein kinase

Targetproteins

ActiveProteinkinase

Secondmessenger

1. Receptors Function as Kinase Enzymes 2. Receptors Activate G Proteins

Cellularresponse

ADP

Cellularresponse

ATP


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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

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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


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

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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

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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

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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 synthesizedby neurosecretory

cells in thehypothalamus

is releasedfrom neuro-

hypophysis intoblood

Integrating Center

Water returned toblood

Response

Increasesblood pressure

Response

Osmoticconcentration ofblood increases

Stimulus

Dehydration

Stimulus

Lowers bloodvolume and

pressure

Stimulus

Osmoreceptorsin CNS monitorconcentration

Sensor

Baroreceptorsin aorta

monitor pressure

Sensor

( – )

Negativefeedback

( – )


Effector

Negativefeedback

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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

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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)

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Glycoprotein hormones

-Dimers, containing alpha () and beta () subunits, each around 100 amino acids

-Thyroid-stimulating hormone (TSH)

-Luteinizing hormone (LH)

-Follicle-stimulating hormone (FSH)

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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

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Portal veins

Hypothalamus

AdenohypophysisSecondary capillaries

Neurohypophysis

Primary capillaries

Primarycapillaries

Axons to primarycapillaries

Neuron cellbodies

Axons to primarycapillaries

Hormones

Portal veins


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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

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Tropic hormones(TSH, ACTH, FSH, LH)

Adenohypophysis

Thyroid, adrenalcortex, gonads

Target Glands

Hormones

Releasing hormones(TRH, CRH, GnRH)

Hypothalamus

( + )

( + )

( + )

Targetcells

( – )

( – )


Negativefeedback

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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

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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

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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

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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

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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

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Th

yro

xin

e p

rod

uc

tio

n

–35 –30 –25 –20 –15

Days from emergence of forelimb

–10 –5 0 +5 +10 +20

TSH stimulates thyroid to producethyroxine.

Forelimbs emerge.

Tail is reabsorbed.

Hypothalamusstimulatesadenohypophysis tosecrete TSH.

Rapid growth Reduced growth,rapid differentiation

Rapid differentiation

Premetamorphosis Prometamorphosis Climax

Receptor stimulation

Hypothalamus stimulation


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The Thyroid Gland

Calcitonin

-A peptide hormone

-Stimulates the uptake of calcium (Ca2+) into bones

-Thus, lowering its levels in the blood

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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

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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

43Increasedblood Ca2+

Response

Low blood Ca2+

Stimulus

Parathyroid glands

Parathyroid

SecretesPTH

( + )( + ) ( + )

( – )

Osteoclastsdissolve Ca(PO4)2

crystals in bone,releasing Ca2+

Effector

Reabsorption ofCa2+, excretion

of PO43–

Increasedabsorption of Ca2+

from intestine (dueto PTH activation

of vitamin D)


EffectorEffector

Ne

ga

tiv

e f

ee

db

ac

k

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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

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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

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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+

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Sympathetic nervoussystem

Sympatheticaxons

Adrenal medullaAdrenal cortex

Adenohypophysis

EffectorCatecholamine HormonesGlucocorticoids

ACTH secreted fromthe adenohypophysis

• Longer term stress response.

( + )

StressStimulus

( – )


Effector

• Effects on lipid and carbohydrate metabolism, immune system, and damage repair.

• Short term stress response.• Effects on cardiovascular system, carbohydrate and lipid metabolism, central nervous system.

Negativefeedback

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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

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The Pancreas

Insulin

-Secreted by beta () 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 () cells of the islets

-Promotes the hydrolysis of glycogen in the liver and fat in adipose tissue

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( + )

( – )( – )

( + )

Blood glucose increased

Stimulus

Blood glucose decreased

StimulusAfter a Meal Between Meals

Effector

Increased glucagonproductionby cells

Effector

Increased insulinproductionby cells

Response

Glycogen hydrolyzed toglucose, then secreted into

blood, increasing blood glucose

Response

Glucose moves fromblood into cells,

reducing blood glucose

Sensor

PancreaticIslets


Ne

ga

tiv

e F

ee

db

ac

k

Ne

ga

tiv

e F

ee

db

ac

k

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Diabetes Mellitus

Diabetics cannot take up glucose from blood

-Type I (insulin-dependent diabetes)

-Individuals lack insulin-secreting 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

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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

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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

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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

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Neurosecretory cells

Larval molt Pupal molt Adult molt

Corpora allata

Prothoracicgland

Brain hormone

Juvenile hormone

Ecdysone

Lowamounts


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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