Endocrine system

Copyright © 2010 Pearson Education, Inc.

Endocrine system


Define Hormone The term hormone is derived from a Greek verb meaning

– to excite or arouse Hormone is a chemical messenger that is released in one

tissue (endocrine tissue/gland) and transported in the bloodstream to reach specific cells in other tissues

Regulate the metabolic function of other cells

Have lag times ranging from seconds to hours

Tend to have prolonged effects

Hormone actions must be terminated – how?


Endocrine versus Nervous system

• Released in synapse

• Close to target cells

• Signal to release by action potential

• Short live effect

• Crisis management

• Released to bloodstream

• Can be distant from target cells

• Different types of signal

• Long term effect

• Ongoing processes

Neurotransmitters Hormones

• Both use chemical communication

• Both are being regulated primarily by negative feedback


Control of Hormone Release Blood levels of hormones:

Are controlled by negative feedback systems Vary only within a narrow desirable range

Hormones are synthesized and released in response to: Humoral stimuli Neural stimuli Hormonal stimuli


Humoral Stimuli

Secretion of hormones in direct response to changing blood levels of ions and nutrients

Example: concentration of calcium ions in the blood

Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)

PTH causes Ca2+ concentrations to rise and the stimulus is removed


Neural Stimuli

• Neural stimuli – nerve fibers stimulate hormone release

• Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines

Figure 16.5b


Hormonal Stimuli Hormonal stimuli – release of

hormones in response to hormones produced by other endocrine organs

The hypothalamic hormones stimulate the anterior pituitary

In turn, pituitary hormones stimulate targets to secrete still more hormones


Classes of Hormones – by chemical structure

• Hormones can be divided into three groups

1. Amino acid derivatives

2. Peptide hormones

3. Lipid derivatives


Chemical structure

AA derivatives

Tyrosine:• Thyroid

hormones• Catecholamines

(Epinephrine, norepinephrine

Tryptophan:Dopamine, serotonin, melatonin

Peptides lipids

small proteins:GH,PRL

Glycoproteins:TSH, LH, FSH

short peptides:ADH, OT

Eicosanoid:prostaglandins

steroids


A Structural Classification of Hormones


Distribution of Hormones in bloodstream

• Hormones that are released into the blood are being transported in one of 2 ways:

• Freely circulating

• Bound to transport protein


Distribution of Hormones in bloodstream• Freely circulating (most hormones)• Hormones that are freely circulating remain functional for less

than one hour and some as little as 2 minutes• Freely circulating hormones are inactivated when: * bind to receptors on target cells * being broken down by cells of the liver or kidneys * being broken down by enzymes in the plasma or

interstitial fluid• Bound to transport proteins – thyroid and steroid

hormones (>1% circulate freely)• Remain in circulation longer

Copyright © 2010 Pearson Education, Inc. Table 7-1

Hormones: Classification


• on the cell membranes of target cells

• In the cytoplasm or nucleus

• Can you tell which hormone group/s will have their receptors on the cell membrane and which in

the cytoplasm?

Receptors for hormones are located:


Mechanisms of Hormone Action

• Two mechanisms, depending on their chemical nature

1. Water-soluble hormones (all amino acid–based hormones except thyroid hormone)

• Cannot enter the target cells

• Act on plasma membrane receptors

• Coupled by G proteins to intracellular second messengers that mediate the target cell’s response

2. Lipid-soluble hormones (steroid and thyroid hormones)

• Act on intracellular receptors that directly activate genes


Indirect effect – through G-protein and 2nd messenger


Receptors on the cell membrane• Hormones do not induces changes in cell activity

directly but via the induction of the appearance and action of other agents

• Hormones are referred to as first messengers and the agents that are activated by the hormones are called second messengers.

• All amino-acid hormones (with exception of the thyroid hormone) exert their signals through a second messenger system:

• cAMP

• PIP


Amino Acid-Based Hormone Action: cAMP Second Messenger

• Hormone (first messenger) binds to its receptor, which then binds to a G protein

• The G protein is then activated• Activated G protein activates the effector enzyme

adenylate cyclase• Adenylate cyclase generates cAMP (second messenger)

from ATP• cAMP activates protein kinases, which then cause cellular

effects


Hormone

Proteinreceptor

G proteinactivated

Hormone

Proteinreceptor

G proteinactivated

Effects on cAMP LevelsMany G proteins, once activated, exert their effects by changing the concentrationof cyclic-AMP, which acts as the second messenger within the cell.

Increasedproduction

of cAMPadenylatecyclaseActs as

secondmessenger

kinase

Activatesenzymes

Opens ionchannels

If levels of cAMP increase,enzymes may be activatedor ion channels may beopened, accelerating themetabolic activity of the cell.

Examples:• Epinephrine and norepinephrine (β receptors)• Calcitonin• Parathyroid hormone• ADh, ACTH, FSH, LH, TSH• Glucagon

Examples:• Epinephrine and norepinephrine (α2 receptors)

In some instances, G proteinactivation results in decreasedlevels of cAMP in thecytoplasm. This decrease hasan inhibitory effect on the cell.

Enhancedbreakdown

of cAMPPDE

Reducedenzymeactivity

Hormone

Proteinreceptor

G protein(inactive)

G proteinactivated

Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 5

Hormone (1st messenger)binds receptor.

Receptoractivates Gprotein (GS).

G proteinactivatesadenylatecyclase.

cAMP acti-vates proteinkinases.

Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).

Receptor

G protein (GS)

Adenylate cyclase

Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)

Hormones thatact via cAMPmechanisms:

EpinephrineACTHFSHLH

Inactiveprotein kinase

Extracellular fluid

Cytoplasm

Activeproteinkinase

GDP

GlucagonPTHTSHCalcitonin

1

2 3 4

5


• Hormone binds to the receptor and activates G protein

• G protein binds and activates phospholipase

• Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers)

• DAG activates protein kinases; IP3 triggers release of Ca2+ stores

• Ca2+ (third messenger) alters cellular responses

Amino Acid-Based Hormone Action: PIP-Calcium


GTP PIP2

IP3

ReceptorGTP

GTP

CatecholaminesTRHADHGnRHOxytocin

Triggers responses of target cell

GDP

Extracellular fluid

Cytoplasm

Inactiveprotein kinase C

Activeprotein kinase C

Phospholipase C

Gq

Ca2+ Ca2+- calmodulin

Hormone

Endoplasmicreticulum

DAG1

2 34 5

5

6

Figure 16.3

Amino Acid-Based Hormone Action: PIP Mechanism


Hormone

Proteinreceptor

G protein(inactive)

G proteinactivated

Hormone

Proteinreceptor

G proteinactivated

Effects on Ca2+ LevelsSome G proteins use Ca2+ as asecond messenger.

Examples:• Epinephrine and norepinephrine (α1 receptors)• Oxytocin• Regulatory hormones of hypothalamus• Several eicosanoids

Activatesenzymes

Calmodulin

PLC,DAG,and IP3

Opening of Ca2+ channels

Release ofstored Ca2+

from ER or SER

Ca2+ acts assecond messenger


Steroid Hormones: Action

Figure 7-7, steps 1–5

1

Cellmembrane

Interstitialfluid

Cytoplasmicreceptor

Endoplasmicreticulum

Nucleus

Nuclear receptor

DNA

Translation

Cell surface receptor

Rapid responses

Transcriptionproduces mRNA

Steroid hormone

Bloodvessel

Proteincarrier

Newproteins

Steroid hormone receptors are in thecytoplasm or nucleus.

Most hydrophobic steroids are bound toplasma protein carriers. Only unboundhormones can diffuse into the target cell.

Translation produces new proteinsfor cell processes.

Some steroid hormones also bind to membrane receptors that use secondmessenger systems to create rapidcellular responses.

The receptor-hormone complex binds toDNA and activates or represses one ormore genes.

Activated genes create new mRNA thatmoves back to the cytoplasm.

2a

2

54

3

1

2a

2

3

4

5


Figure 18-4 Effects of Intracellular Hormone Binding

Receptor

Steroid hormones diffuse through the plasma membraneand bind to receptors in the cytoplasm or nucleus. Thecomplex then binds to DNA in the nucleus, activatingspecific genes.

Diffusion throughmembrane lipids

CYTOPLASM

Target cell response

Alteration of cellularstructure or activity

Translation andprotein synthesis

Binding of hormoneto cytoplasmic ornuclear receptors

Transcription andmRNA production

Gene activation

Binding ofhormone–receptorcomplex to DNA

Nuclearpore

Nuclearenvelope

Receptor

Receptor

Receptor

Target cell response

Alteration of cellularstructure or activity

Translation andprotein synthesis

Transcription andmRNA production

Gene activation

Binding ofhormone–receptorcomplex to DNA

Binding of receptorsat mitochondria andnucleus

Transport acrossplasma membrane

IncreasedATP

production

Thyroid hormones enter the cytoplasm and bind toreceptors in the nucleus to activate specific genes. Theyalso bind to receptors on mitochondria and accelerateATP production.


Location of Receptor

Classes of Hormones

Principle Mechanism of Action

Cell surface receptors (plasma membrane)

Proteins and peptides, catecholamines and eicosanoids

Generation of second messengers which alter the activity of other molecules - usually enzymes - within the cell

Intracellular receptors (cytoplasm and/or nucleus)

Steroids and thyroid hormones

Alter transcriptional activity of responsive genes

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/change.html


How will we approach the endocrine system?

We will group them according to their function in the body: Hormones that control blood glucose levels Hormones that control minerals and water balance Hormones that are involved in growth and metabolism Hormones and the reproductive system


Pancreas structure

Exocrine pancreas (99% of volume)

Cells (pancreatic acini) forming glands and

ducts that secrete pancreatic fluid and enzymes

with digestive function

Endocrine pancreas (1%)

Small groups of cells scattered in clusters

(pancreatic islets) that secrete hormones


How does the body control blood glucose levels

HOMEOSTASISDISTURBED

Rising bloodglucose levels

Beta cellssecreteinsulin.

Ris

ing

bloo

d gl

ucos

e le

vels

Falli

ng b

lood

glu

cose

leve

ls

Falling bloodglucose level

HOMEOSTASISDISTURBED

Alpha cellssecrete

glucagon

HOMEOSTASISRESTORED

HOMEOSTASISRESTORED

Blood glucoselevels decrease

Blood glucose levels increase

Increased breakdown ofglycogen to glucose (inliver, skeletal muscle)

Increased breakdown of fat to fatty acids (inadipose tissue)

Increased synthesisand release of glucose(in liver)

HOMEOSTASISNormal bloodglucose levels(70-110 mg/dL)

Increased amino acidabsorption and proteinsynthesis

Increased triglyceridesynthesis in adiposetissue

Increased conversionof glucose to glycogen

Increased rate ofglucose utilization andATP generation

Increased rate ofglucose transport intotarget cell


• A 51-amino-acid protein consisting of two amino acid chains linked by disulfide bonds

• Insulin is released when glucose levels exceed normal levels (70-110 mg/dl)

Insulin

http://www.chemistryexplained.com/images/chfa_02_img0437.jpg


Endocrine Reflex Pathways: Insulin release

Figure 7-9

Receptor

Efferent path

Effector

Tissue response

Stimulus

Efferent neuron

Sensory neuron

Integrating center

Systemic response

KEYEat a meal

Pancreas

Insulin

Stretch receptorin digestive tract

Glucose uptakeand utilization

CNS

Targettissues

Bloodglucose

Afferent neuron

Efferent neuron

Blood glucose

Neg

ativ

e fe

edba

ck


• Insulin facilitates entry of glucose cells by binding to a membrane receptor

• The complex insulin-receptor make a specific carrier protein (GLUT4) available

• Once at the cell surface, GLUT4 facilitates the passive diffusion of circulating glucose down its concentration gradient into cells.

• Receptors for insulin are present in most cell membranes (insulin-dependant cells)

• Cells that lack insulin receptors are cells in the brain, kidneys, lining of the digestive tract and RBC (insulin-independent cells).

• Those cells can absorb and utilize glucose without insulin stimulation.

Effects of Insulin Binding to its receptors


Effects of Insulin• Acceleration of glucose uptake as a result from an increase of

the number of glucose carrier proteins• Acceleration of glucose utilization and increased ATP

production• Stimulation of glycogen formation in the liver and muscle cells• Inhibits glycogenolysis (break down of glycogen) and

gluconeogenesis (glucose building)• Stimulation of amino acid absorption and protein synthesis• Stimulation of triglyceride formation in adipose tissue

• As a result glucose concentration in the blood decreases


• Released by alpha cells

• A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent (what does it mean?)

• it promotes:

• Glycogenolysis – the breakdown of glycogen to glucose in the liver and skeletal muscle

• Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates in the liver

• Release of glucose to the blood from liver cells

• breakdown of triglycerides in adipose tissue

Glucagon


Other hormones that control glucose levels

Glucocorticoids from the adrenal gland


• Structurally and functionally, they are two glands in one

• Adrenal medulla – neural tissue; part of the sympathetic nervous system

• Adrenal cortex - three layers of glandular tissue that synthesize and secrete corticosteroids

Adrenal (Suprarenal) Glands


Adrenal Cortex• Synthesizes and releases steroid hormones called

corticosteroids• Different corticosteroids are produced in each of the three

layers• Zona glomerulosa – glomerulus- little ball. Secretes

mineralocorticoids – main one aldosterone• Zona fasciculata – glucocorticoids (chiefly cortisol)• Zona reticularis – gonadocorticoids (chiefly androgens)

• Check point - Which of the layers will be part of glucose levels control?


Zona fasciculata - Glucocorticoids (Cortisol/hydrocortisone)

• Main hormones secreted are the Cortisol/hydrocortisone and small amounts of corticosterone

• It protects against hypoglycemia by stimulating catabolism of energy stores.

• While adrenaline is responsible for rapid metabolic responses the glucocorticoids are responsible for long-term stress:

• Glucocorticoids accelerate the rates of glucose synthesis and glycogen formation – especially in the liver

• Adipose tissue responds by releasing fatty acids into the blood and the tissues start to utilize fatty acids as source of energy - glucose-sparing effect (GH has similar effect and will be discussed later)

• Clucocorticoids also have anti-inflammatory effect – inhibit the activities of WBC (use?)


Blood Concentrations of Cortisol Vary Throughout the Day

Figure 23-4


Immunesystem Liver

Functionsuppressed

Gluco-neogenesis

Proteincatabolism

Muscle Adiposetissue

Lipolysis

CRH

ACTH

Cortisol

Hypothalamus

Anteriorpituitary

Adrenalcortex

Circadianrhythm

Stress

long

-loop

neg

ativ

e fe

edba

ck

Pathway For the Control of Cortisol Secretion

Figure 23-3


What happens when we can not control glucose levels?

What can be the reasons for the body’s inability to control glucose levels?

Why do you think it is dangerous to have high or low blood glucose levels?


Diabetes Mellitus (DM)

• Two types:• Type I results from the destruction of beta cells and the

complete loss of insulin (hypoinsulinemia)• Type II is the most common type (90%) and is a result of

decrease sensitivity of cells to insulin (insulin resistance). Type II is accompanied by hyperinsulinemia (what is that? Why?).

• Type II is associated with excess weight gain and obesity but the mechanisms are unclear.

• Other reasons that were associated with type II diabetes: pregnancy, polycystic ovary disease, mutations in insulin receptors and others

Copyright © 2010 Pearson Education, Inc. Table 24.1

Type 1 and Type 2 Diabetes Mellitus


Diabetes Mellitus (DM) effects• Increase in blood glucose due to diabetes causes

• Increase in glucose loss in urine• Dehydration of cells – since glucose does not diffuse

through cell membrane and there is an increase in osmotic pressure in the extracellualr fluid. • In addition, the loss of glucose in the urine causes

osmotic diuresis - decrease in water reabsorption in the kidney.

• The result is • Polyuria – huge urine output and

dehydration.• Polydipsia – excessive thirst


Diabetes Mellitus (DM) effects

• Polyphagia – excessive hunger and food consumption because cells are starving

• Damage to blood vessels and poor blood supply to different tissues

• Increase use of lipids as a source of energy by the cells and increase release of keto bodies – ketosis and changes of blood pH (acidosis). That leads to increased respiratory rate


http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm


Hormones that control minerals and water

We will see the different glands that control: Sodium – Adrenal gland

Which layer and what hormone group? Calcium – Thyroid and parathyroid, kidney Water - hypothalamus


Zona glomerulosa – Mineralocorticoids

• Aldosterone secretion is stimulated by:• Rising blood levels of K+

• Low blood Na+

• Decreasing blood volume or pressure


• The mineralocorticoids are steroids that affect the electrolytes composition of the body extracellular fluids.

• Aldosterone – most important mineralocorticoid • Maintains Na+ balance by reducing excretion of

sodium from the body• Stimulates re-absorption of Na+ by the kidneys• Prevents the loss of Na+ by the kidneys, sweat glands,

salivary glands and digestive system• As a result of Na+ reabsorption there is also water

reabsorption • The retention of Na+ is accompanied by a loss of K+

Zona glomerulosa - Mineralocorticoids


What are the calcium functions in the body?

Provides structure for bones and teeth Transmission of nerve impulses Assists in muscle contraction Part of blood clotting Regulates hormones and enzymes (2nd messanger)


Protein hormones that control calcium

Parathyroid gland – PTH PTH—most important hormone in Ca2+ homeostasis

Thyroid gland – calcitonin Liver and Kidney - Calcitriol – also known as vitamin D3


Calcium Balance in the Body

• Total body calcium = intake output

• Total body calcium is divided into three pools• Extracellular calcium (0.1% of total)

• Intracellular calcium (0.9% of total)

• Calcium in bone matrix (99% of total)

• Ca2+ ions in the extracellular fluid move freely in and out of plasma

• Extracellular fluid calcium is carefully regulated


Calcium Loss in Urine is Hormonally Regulated

Figure 23-17 (5 of 5)

[free Ca2+]0.001 mM

Kidney

Ca2+

in urine

Ca2+

PassivefiltrationCalcitonin

Small intestineDietarycalcium

Ca2+Ca2+ inkidneytubules

PTH Calcitonin

Calcitriol(PTH, prolactin)

PTHCalcitriolCortisol

Electrochemicalgradient

Activetransport

Bone

* Some calcium is secretedinto the small intestine.

Cells

ECF

PTH = parathyroid hormoneKEY

Calciumin feces

[Ca2+]2.5 mM


Simple Endocrine Reflex: Parathyroid Hormone

Figure 7-10

Bone and

kidney

Low plasma [Ca2+]

Plasma [Ca2+]

Bone resorption

Kidneyreabsorption of

calcium

Parathyroid cell

Parathyroid hormone

Production of calcitriolleads to intestinalabsorption of Ca2+

Negative feedback


• PTH release increases Ca2+ in the blood:• Stimulates osteoclasts to digest bone matrix

• Enhances the reabsorption of Ca2+ and the secretion of phosphate by the kidneys

• Increases absorption of Ca2+ by intestinal mucosal

• Rising Ca2+ in the blood inhibits PTH release (what type of control is it?)

• The antagonist is the Calcitonin secreted by the thyroid gland

Effects of Parathyroid Hormone


Calcitriol

Body makes calcitriol from vitamin D Vitamin D can be ingested or produced in the skin

Calcitriol causes an increase in calcium absorption in the intestine

Calcitriol production in the kidneys is promoted by PTH


PTH Control of Calcium Balance

Figure 23-20

PlasmaCa2+

Vitamin D

Endogenousprecursors

Diet(fortified milk, fish

oil, egg yolks)

Liver

25-hydroxycholecalciferol(25(OH)D3)

Calcitriol(1,25-dihydroxycholecalciferol)

Bone,distal nephron, and intestine

Kidney

PlasmaCa2+

Parathyroidhormone

Sunlighton skin


The thyroid gland on the anterior side of the neck. The thyroid gland has a right lobe and a left lobe connected by a narrow isthmus

http://webanatomy.net/histology/endocrine_histology.htm

Thyroid Gland


• A peptide hormone produced by the parafollicular, or C cells

• Lowers blood calcium levels

• Antagonist to parathyroid hormone (PTH)

Calcitonin


• Calcitonin targets the skeleton, where it:• Inhibits osteoclast activity (and thus bone

resorption) and release of calcium from the bone matrix

• Stimulates calcium uptake and incorporation into the bone matrix

• Regulated by a humoral (calcium ion concentration in the blood) negative feedback mechanism

Calcitonin



Hormones that are involved in water balance

Anti diuretic hormone (ADH) – hypothalamus (stored in the neurohypophysis)

Aldosterone (where is it produces? What is the target organ?)

Atrial natriuretic peptide (ANP) - heart


Pituitary gland (Hypophysis)

• Pituitary gland – two-lobed organ that secretes nine major hormones

• Neurohypophysis – posterior lobe (neural tissue) and the infundibulum

• Receives, stores, and releases hormones from the hypothalamus

• Adenohypophysis – anterior lobe, made up of glandular tissue

• Synthesizes and secretes a number of hormones• Identify the 2 parts of the pituitary gland under

the microscope


Figure 18-6a The Anatomy and Orientation of the Pituitary Gland

Optic chiasmInfundibulum

Sellar diaphragm

Pars intermedia

Pars distalis

Pars tuberalis

Anterior lobe

Relationship of the pituitarygland to the hypothalamus

Sphenoid(sella turcica)

Posteriorpituitarylobe

HYPOTHALAMUS

Mamillarybody

Medianeminence

Thirdventricle


Pituitary-Hypothalamic Relationships: Posterior Lobe

• Is a down growth of hypothalamic neural tissue• Has a neural connection with the hypothalamus

(hypothalamic-hypophyseal tract)• Nuclei of the hypothalamus synthesize oxytocin and

antidiuretic hormone (ADH)• These hormones are transported to the posterior pituitary

• Stores antidiuretic hormone (ADH) and oxytocin• ADH and oxytocin are released in response to nerve

impulses• Both use PIP-calcium second-messenger mechanism at

their targets


Copyright © 2010 Pearson Education, Inc. Figure 7-12, steps 1–4

HYPOTHALAMUS

Vein

POSTERIOR PITUITARY

Vesicles are transported down the cell.

Vesicles containing hormone are stored in posterior pituitary.

Hormones are releasedinto blood.

Hormone is made and packaged in cell body of neuron.

1

2

3

4


Neurohypophysis hormones

Hormone Target Effect

Antidiuretic hormone (ADH)

Arginine vasopresin (AVP)

Kidneys Reabsorption of water,

elevation of blood volume and pressure (vasoconstriction)

Oxytocin (OT) Uterus, mammary glands (female)

Ductus deferens and prostate gland (male)

Labor contractions, milk ejection

Contractions of ductus deferens and prostate gland

Hormones that are produced in the hypothalamus and stored in the neurohypophysis


Antidiuretic Hormone (ADH)

• Hypothalamic osmoreceptors respond to changes in the solute concentration of the blood

• What can cause changes in blood concentration?• Body fluids – water

• Electrolytes – in the ECF – mainly sodium

• What is the target organ of the ADH?


Factors Affecting ADH Release

Figure 20-7


Water reabsorption and urine concentration

• Obligatory Water Reabsorption • Is water movement that cannot be prevented

• Usually recovers 85% of filtrate produced

• Facultative Water Reabsorption • Controls volume of water reabsorbed by ADH


Aldosterone and urine concentration• Aldosterone is a steroid secreted by the adrenal cortex

• It is secreted when blood sodium falls or if blood potassium rises

• It is also secreted if BP drops (will be discussed later with the urinary system)

• Aldosterone secreted – increased tubular reabsorption of Na+ in exchange for secretion of K+ ions – water follow

• Net effect is that the body retains NaCl and water and urine volume reduced

• The retention of salt and water help to maintain blood pressure and volume


Atrial natriuretic peptide (ANP) and urine volume

• Secreted from the atrial myocardium in response to high BP

• Has 4 actions that result in the excretion of more salt and water in the urine:

• Dilate afferent arteriole and constricts efferent – increase GFR (more blood flow and higher GHP)

• Antagonized angiotensin-aldosterone mechanism by inhibiting both renin and aldosterone secretion

• Inhibits ADH

• Inhibits NaCl reabsorption by the collecting ducts


Hormones involved in Growth and metabolism

Growth hormone – anterior pituitary gland Thyroid Hormones – hypothalamus, pituitary gland and

thyroid


The anterior lobe• Is an out pocketing of the oral mucosa from epithelial tissue• There is no direct neural contact with the hypothalamus• Hormone production is regulated by the hypothalamus

• Regulatory factors from the hypothalamus arrive directly to the

adenohypophysis through the hypophyseal portal system• Releasing hormones stimulate the synthesis and release of

hormones

• Inhibiting hormones shut off the synthesis and release of hormones

• The hormones of the anterior pituitary (7) are called tropic/trophic hormones because they “turn on” other glands or organs


• Portal system - a system of blood vessels that begins and ends in capillaries. The blood, after passing through one capillary bed, is passing through a second capillary network.

• All blood entering the portal system will reach the target cells before returning to the general circulation

Question – why is such a system important in the communication between the hypothalamus and the

hypophysis?

Hypophyseal portal system


Pituitary-Hypothalamic Relationships: anterior Lobe• The hypophyseal portal system,

consisting of:

• The primary capillary plexus in the infundibulum

• The hypophyseal portal veins

• The secondary capillary plexus


Tropic Hormones of the Anterior Pituitary


The Pituitary Gland: Anterior

Figure 7-13

HYPOTHALAMIC HORMONES

ANTERIOR PITUITARYHORMONES

NONENDOCRINETARGETS

ENDOCRINE TARGETSAND THE HORMONESTHEY SECRETE

Somatostatin

GHRH* GnRH

Portal system

Anterior pituitary

FSH LH

Neurons in hypothalamussecreting trophic hormones

To target tissues

GH

Endocrine cellsof the gonads

Endocrinecells

Many tissues

Germ cellsof the gonads

Thyroid gland

Thyroid hormones

Adrenalcortex

Cortisol

Liver

IGFs AndrogensEstrogens,

progesterone

PRFs TRH CRH

TSH ACTHProlactin

Breast

Dopamine*

(Gonadotropins)


Normal Growth in Humans

• Growth is a continuous process that varies in rate, and depends on four factors

1. Growth hormone and several other hormones (for example – hormones that control calcium and glucose)

2. An adequate diet

3. Absence of chronic stress

4. Genetic potential for growth


Growth Hormone (GH) or somatotropin

• GH is an anabolic (tissue-building) hormone• Stimulate most body cells to increase in size and

divide by increasing protein synthesis

• Major target tissues are bone, cartilage and skeletal muscle

• GH release is regulated factors released by the hypothalamus:

• Growth hormone–releasing hormone (GHRH)

• Growth hormone–inhibiting hormone (GHIH) (somatostatin


SomatostatinGHRH

GH

Hypothalamus

Liver andother tissues

Insulin-likegrowth factors

Anteriorpituitary

Circadian rhythmStress and cortisol

Fasting

Bone andtissue growth

Cartilagegrowth

Bloodglucose

Growth Hormone Control Pathway

Figure 23-13


Effects of Growth Hormone

• Growth Hormone has several distinct cellular effects• Increases plasma glucose

• Increases bone and muscle growth

• Stimulates protein synthesis

• Stimulates liver to secrete IGFs

• IGFs stimulate cartilage growth


Growth Hormone (GH) or somatotropin• The stimulation of growth by GH involves 2

mechanisms:

• The primary one is indirect and more understood:

• GH influence the liver, skeletal muscle, bone, and cartilage to release insulin-like growth factors (IGF)/somatomedins

• The IGF binds to specific receptors on cells and increase the uptake of amino acids and their incorporation into new proteins


Growth Hormone (GH) or somatotropin• Direct effects

• In ET and CT stimulate cell division and differentiation (the subsequent cell growth is mediated by IGF)

• In adipose tissue GH stimulates the breakdown of stored triglycerides by adipocytes and the release of fatty acids to the blood. That promotes the use of fatty acid for energy instead of the use of glucose (glucose-sparing effect)


Anterior pituitary hormones

Region Hormone Target Effect Hypothalamic regulatory hormone

Thyroid-stimulating hormone (TSH/ thyrotropin)

Thyroid gland Secretion of thyroid hormones (T3, T4)

Thyrotropin-releasing hormone (TRH)

Adrenocorticotropic hormone (ACTH)

Adrenal cortex (zona fasciculate)

Secretion of glucocorticoids (cortisole, corticosterone)

Corticotrophin-releasing hormone (CRH)


Figure 18-11b The Thyroid Follicles

The regulation of thyroid secretion

HomeostasisDisturbed

HOMEOSTASIS

HomeostasisRestored

Thyroid folliclesrelease T3 and T4

Thyroidgland

TSH

Anteriorlobe

Pituitarygland

Hypothalamusreleases TRH

TRH

Anteriorlobe

Decreased T3 and T4 concentrationsin blood or lowbody temperature

Normal T3 and T4 concentrations,

normal bodytemperature

Increased T3 and T4 concentrationsin blood


TSH

T4, T3

T4 T3

Hypothalamus

Anteriorpituitary

Thyroidgland

Systemicmetabolic

effects

Stimulus

Integrating center

Efferent pathway

Effector

Systemic response

TRH

Tonic release

KEY

Negative feedback

Thyroid Hormone Control Pathway

Figure 23-11


• Thyroid hormone – major metabolic hormone

• Consists of two related iodine-containing compounds

• T4 – thyroxine; has two tyrosine molecules plus four bound iodine atoms

• T3 – triiodothyronine; has two tyrosines with three bound iodine atoms

Thyroid Hormone


Synthesis of Thyroid Hormone

• Thyroglobulin is synthesized by the follicular cells and released into the lumen

• Iodides (I–) are actively taken into the cell by membrane carrier proteins

• The iodide ions diffuse to the apical surface of the cells (these cells are facing towards…?), oxidized to iodine (I2) by the enzyme thyroid peroxidase and released to the colloid.

• Iodine attaches to tyrosine in the thyrogobulin, forming T1 (monoiodotyrosine, or MIT), and T2 (diiodotyrosine, or DIT)


Synthesis of Thyroid Hormone

• Iodinated tyrosines link together to form T3 and T4

• Coupling reaction

MIT + DIT T3 / triiodothyronine

DIT + DIT T4 / thyroxin (tetraiodothyronine)

• The colloid is then endocytosed and combined with a lysosome, where T3 (10%) and T4 (90%) are cleaved and diffuse into the bloodstream

• 75% of the T4 and 70% of the T3 are transported attached to thyroid-binding protein (TBGs) and the rest to a special albumin


Thyroid Hormones are Made from Iodine and Tyrosine

Figure 23-8


Thyroid Hormone

• Although the major thyroid hormone that is being produced is the T4 (90%) T3 is the one responsible for the TH effects

• Enzymes in the kidneys, liver and other tissues convert T4 to T3

Copyright © 2010 Pearson Education, Inc. Figure 16.9, step 7

To peripheral tissues

T3

T3

T3

T4

T4

Lysosome

Tyrosines (part of thyroglobulinmolecule)

T4

DIT (T2)Iodine

MIT (T1)

Thyro-globulincolloid

Iodide (I–)

RoughER

Capillary

Colloid

Colloid inlumen offollicle

Thyroid follicle cells

Iodinated tyrosines arelinked together to form T3

and T4.

Iodideis oxidizedto iodine.

Thyroglobulin colloid isendocytosed and combinedwith a lysosome.

Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream.

Iodide (I–) is trapped(actively transported in).

Thyroglobulin is synthesized anddischarged into the follicle lumen.

Iodine is attached to tyrosinein colloid, forming DIT and MIT.

Golgiapparatus

1

2

3

4

5

6

7


Figure 18-11a The Thyroid Follicles

Folliclecavity

Thyroglobulin(contains T3 and T4)

FOLLICLE CAVITY

Endocytosis

Lysosomaldigestion

Thyroglobulin

Other amino acids

Tyrosine

Diffusion

DiffusionTSH-sensitiveion pump FOLLICLE CELL

CAPILLARY

Iodide (I–)

T4 & T3

TBG, transthryretin,or albumin

The synthesis, storage, and secretion of thyroid hormones.

Iodide(I+)

T4T3


Thyroid Hormone and target cells

• Thyroid hormones influence almost every cell of the body

• Inside the cells they bind to receptors in one of 3 locations:

• In the cytoplasm – storage of thyroid hormones to be released if the intracellular levels decrease

• On the mitochondria surface – increase rate of ATP production

• In the nucleus – activate genes that control the synthesis of enzymes that involve with energy production and utilization (for example increase of production of sodium-potassim ATPase that uses ATP)


Functions of Thyroid Hormones Elevates rates of oxygen consumption and energy consumption;

in children, may cause a rise in body temperature Increases heart rate and force of contraction; generally results in

a rise in blood pressure Increases sensitivity to sympathetic stimulation Stimulates red blood cell formation and thus enhances oxygen

delivery Stimulates activity in other endocrine tissues (E, NE for

example) Accelerates turnover of minerals in bone Activate genes that code for enzymes that are involved in

glycolysis (Glucose oxidation) In children, essential to normal development of Skeletal,

muscular, and nervous systems

Endocrine system

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