mechanism hormone disease (lec 3).ppt

7/27/2019 mechanism hormone disease (lec 3).ppt

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Mechanisms of endocrine disease

Endocrine disorders result from hormonedeficiency, hormone excess or hormone

resistance

Almost without exception, hormonedeficiency causes disease

One notable exception is calcitonin

deficiency


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Cellular Mechanisms of Hormone Action

Target cellrecognize, bind and

initiate

Up regulation

Down regulation

Hormone effects

Direct stimulation Permissive facilitates maximum

response/function


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Deficiencyusually is due to destructiveprocess occurring at gland in which hormone

is producedinfection, infarction, physical

compression by tumor growth, autoimmune

attack


Type I Diabetes


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Deficiency can also arise from geneticdefects in hormone productiongene

deletion or mutation, failure to cleave

precursor, specific enzymatic defect (steroid

or thyroid hormones)


Congenital Adrenal Hyperplasia


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Inactivating mutations of receptors cancause hormone deficiency


Testicular Feminization Syndrome


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Hormone excess usually results in disease Hormone may be overproduced by gland

that normally secretes it, or by a tissue that

is not an endocrine organ. Endocrine gland tumors produce hormone in

an unregulated manner.


Cushings Syndrome


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Exogenous ingestionof hormone is thecause of hormoneexcessfor example,glucocorticoid excessor anabolic steroidabuse



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Activating mutations of cell surface receptorscause aberrant stimulation of hormoneproduction by endocrine gland.

McCune-Albright syndrome usually

caused by a mutation in a gene calledGNAS1 (Guanine Nucleotide bindingprotein, Alpha Stimulating activitypolypeptide 1).



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Malignant transformation of non-endocrine tissue causesdedifferentiation and ectopic productionof hormones

Anti-receptor antibodies stimulatereceptor instead of block it, as in thecase of the common form of

hyperthyrodism.


Graves Disease


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Alterations in receptor number and functionresult in endocrine disorders

Most commonly, an aberrant increase in the

level of a specific hormone will cause adecrease in available receptors


Type II diabetes


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Adrenal Gland

Adrenal glands are located on the top of both kidneys.

Each gland consists of a medulla, the center of the

gland, encased by a cortex.


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Adrenal Glands Adrenal cortex

80%of an adrenal glands total weight

Zona glomerulosaaldosterone 15%

Zona fasciculataglucocorticoids 78%

Zona reticularisandrogens and estrogens(others)

7%

Adrenal medulla

Innervation by SNS


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Adrenal Glands


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-Inner part medulla:

-Chromaffin cells-Source of catecholamines (Epi/NEpi),

-Innervated by pre-ganglionic sympathetic fibers; forms an

extension of the sympathetic nervous system (fight/flight).

-Outer part cortex:

-Source of steroid hormones

-Glucocorticoids, mineralocorticoids and sex steroids

Anatomy/Physiology of Adrenal Gland


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DHBR

NADP+NADPH

from phe, diet, or protein

breakdown

Tyrosine L-Dopa

H2OO2

Tyrosine hydroxylase(rate-determining step)

BH2BH4

1

Dopa

decarboxylase

CO2

Dopamine

pyridoxalphosphate

2

Dopamine hydroxylase

ascorbateH2O

Norepinephrine

O23

NMT

SAM SAH

Epinephrine

4

Biosynthesis of catecholamines. BH2/BH4, dihydro/tetrahydrobiopterin;

DHBR, dihydrobiopterin reductase; NMT, N-CH3 transferase; SAH, S-

adenosyl-homocysteine; SAM, S-adenosylmethionine

Parkinsons disease: local

deficiency of dopamine

synthesis; L-dopa boostsproductionNMT specific to

adrenal medulla

SAM from

metabolism of

Met

DPN OHase in neuro-

scretory granules


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.....

...

acetylcholine

Adrenal Medulla

Chromaffin Cell

Neuron

Acute

regulation

Tyrosine

L-DopaDPN

DPN

NE

granuleinduction

Chronic

regulation

Stress

Hypothalamus

ACTH

Cortisolfrom adrenal

cortex via intra-

adrenal portal

system

EpinephrinePNMT

NE

neuro-

secretory

granules

E E E

NE E

Regulation of the release of

catecholamines and synthesis of

epinephrine in the adrenal medulla

chromaffin cell.

promotesexocytosis

................

EEE

ENEE

E E

NE

E

Ca2+


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Norepinephrine

Epinephrine COMT + MAO

Vanillylmandelic acid

Figure 3. Degradation of epinephrine, norepinephrine and dopamine via monoamine

oxidase (MAO) and catechol-O-methyl-transferase (COMT)

Neuronal re-uptake and degradation of catecholamines quickly

terminates hormonal or neurotransmitter activity.

Cocaine binds to dopamine receptor to block re-uptake of dopamine

Dopamine continues to stimulate receptors of the postsynaptic nerve.

Dopamine Homovanillic acid

COMT + MAO


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Classification of Adrenergic Hormone Receptors

Receptor Agonists SecondMessenger

G protein

alpha1 (1) E>NE IP3/Ca2+; DAG Gq

alpha2 (2) NE>E cyclic AMP Gi

beta1 (1) E=NE cyclic AMP Gsbeta2 (2) E>>NE cyclic AMP Gs

E = epinephrine; NE = norepinephrine

Synthetic agonists:

isoproterenol binds to beta receptorsphenylephrine binds to alpha receptors (nose spray action)

Synthetic antagonists:

propranolol binds to beta receptors

phentolamine binds to alpha receptors


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Metabolic and muscle contraction responses to catecholamine binding tovarious adrenergic receptors.

Process 1-receptor(IP3, DAG)

2-receptor

( cAMP)1-receptor

( cAMP)2-receptor( cAMP)

Carbohydrat

e

metabolism

liver

glycogenolysis

No effect No effect

liver/muscle

glycogenolysis;

liver gluconeogenesis; glycogenesis

Fat

metabolismNo effect lipolysis lipolysis No effect

Hormone

secretionNo effect

insulin,renine

secretion

No effect insulin, glucagon and

renin secretion

Muscle

contraction

Smooth

muscle - blood

vessels,

genitourinary

tractcontraction

Smooth

muscle -

some

vascular;

GI tractrelaxation

Myocardial

- rate,force

Smooth muscle

relaxation - bronchi,

blood vessels,

GI tract, genitourinary

tract


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1 or2receptor

ATPcyclic AMP

Gs

s

GTP

inactive

adenylylcyclase

GTP

ACTIVE

adenylyl

cyclase

inactive

adenylylcyclase

2 receptor

Mechanisms of1, 2, and 2 agonist effects on adenylyl cyclase activity

Gi

i

GTPs

GTP

i

X


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" FIGHT OR FLIGHT" RESPONSE

epinephrine/ norepinephrine major elements in the "fight or flight" response

acute, integrated adjustment of many complex processes in organs vital to the

response (e.g., brain, muscles, cardiopulmonary system, liver)

occurs at the expense of other organs less immediately involved (e.g., skin, GI).

epinephrine:rapidly mobilizes fatty acids as the primary fuel for muscle action

increases muscle glycogenolysis

mobilizes glucose for the brain by hepatic glycogenolysis/gluconeogenesis

preserves glucose for CNS by insulin release leading to reduced glucoseuptake by muscle/ adipose

increases cardiac output

norepinephrine elicits responses of the CV system - blood flow and insulinsecretion.


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ADRENAL CORTEX-DERIVED STEROIDS


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Adrenal Cortex

all hormones derived from cholesterol Stimulated by adrenocorticotropic hormone (ACTH)

Glucocorticoid hormones

Direct effect on carbohydrate metabolism

Anti-inflammatory and growth suppression effects Influences awareness and sleep habits

Inhibits bone matrix-protein matrix

Cortisol most potent naturally occurring


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Adrenal Cortex

Mineralocorticoid hormones

Aldosterone Na+ uptake in epithelial cells

distal nephrons

Na retention with loss of K+ and H+

Regulation by the renin-angiotensin

system

Na+ and H2O depletion K+ excreteion

blood volume


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Adrenal Cortex-derived Stero ids

Class Major Effects

Glucocorticoids Cortisol Glucose metabolism

control

Mineralocorticoids Aldosterone Na/K/H20 control

Sex steroids DHEA Androgen precursors

Androstendione


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SECRETION OF INDIVIDUAL

STEROID HORMONES IS

RESTRICTED TO SPECIFIC

REGIONS OF THE ADRENAL

CORTEX

CAPSULE

MEDULLARETICULARIS

MEDULLA

SYNTHESIS OF ADRENAL CORTEX HORMONES


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SYNTHESIS OF ADRENAL CORTEX HORMONES


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Hypothalamus

Anterior pituitary

Adrenal cortex

Corticotropin-releasingfactor (CRF)

Adrenocorticotropic hormone

(ACTH)

Glucocorticoids

(especially cortisol)

Hypoxia

Hypoglycemia

Hyperthermia

Exercise

Cortisol

insufficiency

Stress

Diurnal

rhythms

( - )

Somatostatin

Hypothalamic

lesions

( - )

(+)

(+)(+)


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minusside

chain

ALL STEROIDOGENIC TISSUES

CHOLESTEROL(C27)

+ 3-keto

+ 11-OH

PROGESTERONE

+3-keto

+ 21-OH

+ 3-keto

+ 11-OH

+ 21-OH

+ 17-OH

CORTISOL (C21)

CORTICOSTERONE

ALDOSTERONE(C21)

+ 20-keto

+ 17-OH

PREGNENOLONE(C21)

ANDROSTENEDIONE(C19)

+ 18-ALDEHYDE

TESTOSTERONE

ESTRADIOL (C19)

GONADS

ADRENAL CORTEX

ESTRONE

STEROID SYNTHESIS

DEHYDROEPIANDROSTERONE

DHEA

17-OH PROGESTERONE

DEHYDROEPIANDROSTERONESULFATE (C19 :DHEA-S)

+ 3-keto

aromatase

17-OH PREGNENOLONE

DIHYDROTESTOSTERONE (C19)

sulfotransferasedesmolase

desmolase

aromatase

Adrenals


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ENDOPLASMIC RETICULUM

OXIDATION OF STEROID NUCLEUS

BY SPECIFIC P-450 HYDROXYLASES

ALDOSTERONE

ANDROGENPRECURSORS

SYNTHESIS AND SECRETION OF STEROID HORMONES BY ADRENAL CORTEX

GONADS

Cholesterol in

Intracellular

Lipid droplets

2

1

3

KIDNEY

DIFFUSION OF STEROIDS

OUT OF CELLCORTISOL

CHOLESTEROL IS TAKEN UP INTO MITOCHONDRIA

EITHER DIRECTLY FROM PLASMA LDL/HDL OR FROM

INTRACELLULAR CHOLESTEROL ESTERS STORED

IN LIPID DROPLETS

UPTAKE OF CHOLESTEROL

ESTER FROM LDL AND HDL

IN PLASMA

StAR facilitates transfer of

cholesterol molecules between

inner and outer membranes

4

17-OH PROGESTERONEREMOVAL OFSIDE CHAIN

P450c11

11-HYDROXYLASE

h b l ff f l d


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The metabolic effects of glucocorticoids

They increase glucose production by:

1. Increasing the supply of amino acids to the liver2. Activating the expression of genes of gluconeogenic enzyme

Promote lipolysis in peripheral tissues by inducing enzyme synthesis

(Increase mobilization of peripheral fat)

When at very high levels can cause lipogenesis in face and trunk

When at a very high levels has catabolic effect on proteins in peripheral

tissues and anabolic effect in the liver

h b l ff f l d


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The metabolic effects of glucocorticoids

When at very high levels can cause lipogenesis in face and trunk


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Cortisol (hydrocortisone) and synthetic glucocorticoids(prednisone): Potent anti-inflammatory and

immunosuppressive agent [topical, oral, aerosolized, injection]

Therapeutic Effects of Glucocorticoids

-used to relieve symptoms of inflammation [swelling, heat,

redness, and pain];

-used in cases of insufficient synthesis (hormone replacement);

-used to treat certain forms of arthritis; skin, blood, kidney, eye,thyroid, and intestinal disorders (e.g., colitis); severe allergies; and

respiratory conditions such as asthma.

-used in the treatment of certain types of cancer.

How glucocorticoids suppress immune and inflammatory reactions


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A glucocorticoid interaction with its receptor results in increasing the transcription

of the protein IB, which binds and inhibits the activity of NF-B, a a transcriptionalactivator that stimulates transcription of genes for inflammatory cytokines. NF-B

is normally sequestered in an inactive state through association with IB proteins.(TNF is a proinflammatory cytokine.)

Glucocorticoid induction of

IB synthesis through GCbinding to its intracellular

receptor and stimulating trans-

cription of the gene.

IB binds toand inhibits the

nuclear translo-

cation of NF-B.

NF-B stimulates theultimate production of

inflammatory cytokinesTumor necrosis factor (TNF)binding to its receptor leads to

the ultimate degradation of IB

How glucocorticoids suppress immune and inflammatory reactions

mediated by cytokines


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Cortisol (the naturally-occurring glucocorticoid)

levels are regulated by a hypothalamus-

pituitary-adrenal hormone axis.

Corticotropin releasing hormone

(CRH) controls adrenocortioctropic hormone(ACTH) release from the pituitary.

ACTH is a trophic hormone that

stimulates:

-synthesis and secretion of cortisol and

-growth of the adrenal gland.

When cortisol levels increase, CRH and ACTH

secretion/release are reduced.

Adrenal Gland Steroids


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Mineralocort ic oids (e.g. aldosterone)-enhance renal tubular retention of Na+, HCO3- and water

and increase excretion of K+: this increases serum Na and

decreases serum K

-increased blood volume and pressure

Mineralocorticoids

Removal of the adrenal glands leads to death within just a few days due to:

-the concentration of potassium in extracelluar fluid becomes dramatically

elevated;

-urinary excretion of sodium is high and concentrations of sodium inextracellular fluid decreases significantly;

-volume of extracellular fluid and blood plummet;

-the heart begins to function poorly, cardiac output declines and shock ensues


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Control over aldosterone secretion is multifactorial:

-The two most significant regulators of aldosterone secretion are:

Concentrations of K+ in extracellular fluid: Small increases in blood

levels of potassium strongly stimulate aldosterone secretion.

Angiotensin II: Activation of the renin-angiotensin system as a result of

decreased renal blood flow (usually due to decreased vascular volume)

results in release of angiotensin II, which stimulates aldosterone secretion

Control of Aldosterone Secretion


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Adrenal Insufficiency (Addisons disease, 1:100,000)

Primary Adrenal Insufficiency:

-most common cause is autoimmune-mediated destruction of the adrenal

glands (>80%)

-secondary to tuberculosis, chronic fungal infections, infection by

cytomegalovirus (CMV), metastasis to the glands by cancer cells (~20%)

Secondary Adrenal Insufficiency:

-Addisons Disease caused by inadequate secretion of ACTH by the

pituitary gland;-may arise due to the prolonged or improper use of glucocorticoid

hormones( temporary);

Disorders of the Adrenal Gland

Di d f h Ad l Gl d


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Cushings Syndrome

-Cushing's Syndrome is EITHER a disease caused by anexcess of cortisol production, or a disorder resulting fromexcessive use of glucocorticoids

Disease-related excess production of cortisol (2 types):

1) Excess ACTH Production:

Ex. A pituitary tumorproducing too much ACTH

stimulates adrenal growth and increases cortisol(>70%); Also "ectopic" ACTH production (30%)

2) Adrenal cortex tumours: Tumours can be benign

(an adenoma), or malignant (a carcinoma). Usually

found on only one side.

Disorders of the Adrenal Gland


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Stress = any condition that threatens homeostasis

GAS (General Adaptation Syndrome) is our bodiesresponse to stress-causing factors

Three phases to GAS

Alarm phase (immediate, fight or flight, directed

by the sympathetic nervous system and

dominated by the catecholamines)

Resistance phase (dominated by

glucocorticoids) Exhaustion phase (breakdown of homeostatic

regulation and failure of one or more organ

systems)

Hormones and stress

The General Adaptation Syndrome


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Figure 18.21


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Retinoid Hormones

Isoprenoid hydrophobichormones.

The pro-hormone, retinol, ismade in the liver.

Retinol is converted to the

hormone, retinoic acid, bymany tissues.

Retinoic acid regulates cellgrowth and development inmost cells, but the principaltargets are the cornea, skin

and epithelia.

Excess Vitamin A can causebirth defects and liverdamage.

Severe acne is treated with

retinoid creams.


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THYROID HORMONES

G


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The Thyroid Gland

Figure 18.11b, c

Thyroglobulin is a protein rich in Tyr (100Tyr/1molecule)


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Synthesis of T3 and T4

The thyro id gland:Synthesizes and secretes triiodothyronine-T3 andthyroxine-T4

-the only body tissue that can accumulate iodide

Steps of thyroid hormone synthesis

-accumulat ion of iod idevia a specific iodide pump.

-iod inati t ion of tyros ineproduces monoiodotyrosine (MIT) and

diiodotyrosine (DIT)

- cou pl ing react ion:Synthesis of MIT/DIT:

-MIT +DIT produces T3 (3 iodine)-DIT+DIT, T4 (4 iodine).

-MIT/DIT are complexed with thyroglobulin.

-Thyroglobin pro teolys isliberates T3 and T4

- Released hormones are secreted: 5(T4) to

1(T3).

SYNTHESIS OF THYROID HORMONES STEP 1 IODINATION


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TYROSINE

IODINATION

TYROSINE

MONOIODOTYROSINE(MIT)

DIIODOTYROSINE (DIT)

I

I

NH2

TYROSINE

IODINATION

I

I

SYNTHESIS OF THYROID HORMONES: STEP 1 - IODINATION

Approximately 10% of the tyrosine residues on the

550 amino acid residue Thyroglobulin molecule may

become iodinated by the enzyme - thyroid

peroxidase acting on the colloid at the luminal

surface of the thyroid follicle. These reactions only

occur in the thyroid at specific residues in

Hormonogenic sites located at the extreme ends of

the Thyroglobulin molecule.

Tyr

Tyr

THYROGLOBULIN

THYROGLOBULIN

THYROGLOBULIN-

SYNTHESIS OF THYROID HORMONES: STEP- 2 COUPLING OF IODOTYROSINES


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Thyroglobulin

CH2CHCOOH

Thyroglobulin

I

I

Tyr

3,5,35-tetraiodothyronine

SYNTHESIS OF THYROID HORMONES: STEP 2 COUPLING OF IODOTYROSINES

CH2CHCOOH

NH2+HO

II

I

Tyr

NH2

T4

Thyroglobulin

I

I

Tyr CH2CHCOOH

NH2

CH2CHCOOH

I

Tyr

NH2

Thyroglobulin

Tyr

II

I

Tyr O+

IT3

3,5,3-Triiodothyronine

Coupling of iodotyrosine moities results in the loss

of the peptide linkage to thyroglobulin allowing thyroid

hormones to diffuse across the cell membrane

II

Tyr

II

I

Tyr O

I

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55

HO

HO

HO

HO

HO

3,5,35-tetraiodothyronine


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CH2CHCOOH

NH2

CH2CHCOOH

3,3,5-Triiodothyronine (reverse T3)

NH2

Tyr

II I

Tyr O

rT3

I

3,5,3-Triiodothyronine (T3)

II

Tyr

II

I

Tyr O

T4I

T3

Tyr

II I

Tyr O

I

5- deiodination5-deiodination

CH2CHCOOH

ACTIVATION PATHWAY

In peripheral tissuesDEACTIVATION PATHWAY

NH2

STEP 3DEIODINATION

SELENODEIODINASES

SECRETION OF THYROID HORMONE


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TG

IODINATIONOF THYROGLOBULIN

BY THYROID PEROXIDASE

DIFFUSION OF THYROXINE

THROUGH CELL MEMBRANE

DEGRADATION OF

THYROGLOBULIN

FUSION OF PHAGOSOME

WITH LYSOSOMES

ENDOCYTOSIS OF

COLLOID IN FOLLICLE BY

PSEUDOPOD

TG

TG

TG

T4

T4 T3>> >

I

IODIDE UPTAKE

BY Na/I

SYMPORTER

IODIDE IN

ECF~20nM

DEGRADATION

AND

RECYCLING

OF MIT/DIT

BY DEIODINASES FREE THYROXINE RELEASED FROM

PROTEIN INTO CYTOPLASM

TG

2

1

3

4

5

6

7

8

Additional metabolism??


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THYROID HORMONES

HORMONE

RELATIVE

POTENCYPRODUCTION

t(g/day)

4-8 (24)*

BOUND TO

PLASMAPROTEINS

(%)

-

99.95

(days)

80- 90 8

0.04 99.8 0.1

+ + + +

rT3

VALUES IN PARENTHESES INDICATE PERIPHERAL CONVERSION

2-3 (27) *

1-3

6-7+T4

T3

*

(g/dL)

PLASMA

CONCENTRATION

0.3 99.7

R l d T3/T4 R l


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Regulated T3/T4 Release

T3/T4 synthesis/release is tightly regulated:

-reduced T3/T4 stimulates TRH release from the

hypothalamus (HPT) which then causes TSH

release from the pituitary (PIT).

TSH stimulates:1) T3/T4 synthesis and secretion

2) thyroid gland growth.

When T3/T4 levels increase, negative feedback

shuts off TRH and TSH secretion.


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Physiological Actions of T3/T4

Play a Central Role in Regulating :

-growth/development of most cells,

-basal metabolic rate and temperature (stimulate cellularrespiration)

-cardiac output by increasing rate/force of contraction,

-metabolism of cholesterol to bile acids,

-LDL receptor expression in hepatocytes,

-TSH secretion

THYROID HORMONES ARE ESSENTIAL TO LIFE!


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Symptoms include:fatigue/weakness, weight gain/difficultylosing weight, coarse/dry hair, dry/rough pale skin, cold intolerance,

muscle cramps/muscle aches, constipation, depression, irritability,

memory loss, abnormal menstrual cycles, decreased libido

-Myxedema coma:A medical emergency characterized byhypothermia, hypotension, hypoventilation and bradycardia

represents the extreme expression of severe hypothyroidism

Hypothyroidism (Myxedema)

Reduced circulating T3/T4 levels


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Problems with the Thyroid Gland

Hyperthyroidism:

high metabolic rate, hyperactivity, sensitivity to heat, protruding eyes Graves disease: when hyperthyroidism is due to an autoimmune problem

(TSH is mimicked by autoantibodies)

Hypothyroidism:

in the adult: myxedema- low metabolic rate, sensitivity to cold,sluggishness, weight gain/difficulty losing weight, coarse/dry hair, dry/roughpale skin, constipation, depression, irritability, memory loss, abnormalmenstrual cycles, decreased libido

in an infant: cretinism-- stunted growth, mental retardation, abnormal boneformation

Hashimotos disease: when hypothyroidism is due to an autoimmuneproblem (autoantibodies attack and destroy follicular cells)

goiterno T3 and T4 can be made because not enough iodides wereingested.


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Pr imary Hypothy ro id ism (Myxedema)

-When synthesis of T3/T4 is low, no feedbackinhibition of TSH occurs and TSH levels rise.

-TSH stimulation of the thyroid gland is

increased and lead to:

-the lack of T3/T4 synthesisin primary hypothyroidism leads to

TSH-mediated increases in size (goiter).


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When the pituitary can't make TSH

there is no signal to the thyroid gland

to make T3/T4. Thus secondary

hypothyroidism is (i.e. pituitary-

mediated) associated with decreasedT3/T4 AND TSH and thyroid atrophy.

Secondary Hypothyro id ism


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Primary hyperthyroidism: Thyroidsecretes T3/T4 in a TSH unregulated

fashion

Symptoms:

-heart palpitations, heat intolerance,

nervousness, insomnia, breathlessness,

increased bowel movements, light/absent

menstrual periods and fatigue

Primary Hyperthyroidism


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Loss of T3/T4-mediated negative

effects on TSH release by pituitary

-the thyroid is chronically stimulatedto synthesize and secrete T3/T4

and to grow. Thus ,goiter is also a

symptom of secondary

hyperthyroidism

Secondary Hyperthyroidism


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Relief of direct symptoms: Drugs that inhibit thyroid hormone

production/release (methimazole, propylthiouracil (PTU):

-Inhibit hrmone synthesis (iodine organification)

-Inhibit MIT coupling

Limitations: The symptoms associated with hyperthyroidism return

when the drugs are discontinued.

Hyperthyroidism-Treatments


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Radioactive Iodine:[135I]-most widely recommended permanent treatment of

hyperthyroidism

-treatment takes advantage of the fact that only thyroid cellscan incorporate iodine

-[135I] emits gamma () radiation: Directly kills thyroid cells

-There is no evidence that [135I] treatment for hyperthyroidism

causes cancer of the thyroid gland or of any other tissue

Hyperthyroidism-Treatments


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BUT IS CALCITONIN AN IMPORTANT PHYSIOLOGICAL SUBSTANCE?

The observation that calcitonin (CT) at supraphysiological doses is hypocalcemic, led to the mistaken

conclusion that it was important for calcium homeostasis and this idea has persisted to this day.

Despite these findings there is no apparent pathology due to CT excess or deficiency and there is no

evidence that circulating CT is of substantial benefit to any mammal.

Mammalian CT at physiological doses is not essential and very likely the CT gene has survived

because of the genes alternate mRNA pathway to produce calcitonin-gene-related peptide CGRP

found in neural tissues.

HIRSCH,PF and BARUCH H, ENDOCRINE 2003, 201-208

CALCITONIN IS SECRETED FROM THE THYROID PARAFOLLICULAR CELLS


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THE PARATHYROID HORMONE

Parathyroid Gland


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Parathyroid Gland

This gland only secretes

one hormone:

Parathyroid Hormone(or PTH)

PTH function (we began

learning this when we

studied bone):

increases bloodcalcium (Ca2+) levels

and decreases

blood phosphate

(PO42-) levels

PTH function (cont inued)


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PTH function (cont inued)

How does PTH work?

PTH causes Ca2+ & PO42- to be released from

bone into blood (by increasing osteoclast

activity)

PTH decreases the excretion of PO42- ionsthrough urine

PTH increases calcitriol production, so that more

Ca2+ is absorbed during digestion

PTH is regulated by blood calcium levels-- not by

other glands!

The Regulation of Calcium Ion Concentrations


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THE PANCREATIC HORMONES

The pancreatic islets


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Clusters of endocrine cells within the

pancreas called Islets of Langerhans or

pancreatic islets Alpha cells secrete glucagons

Beta cells secrete insulin

Delta cells secrete GH-IH F cells secrete pancreatic polypeptide

The pancreatic islets

The Endocrine Pancreas


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The Endocrine Pancreas

Figure 18.18a, b

BLOOD FLOWS RADIALLY FROM CENTER OF ISLET

ISLETS OF LANGERHANS


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BLOOD FLOWS RADIALLY FROM CENTER OF ISLETTO THE PERIPHERY FACILITATING PARACRINE

INHIBITION OF GLUCAGON SECRETION BY INSULIN

VENOUS BLOOD

MANTLE FORMED BY CELLSSECRETING GLUCAGON (20-25%)

CORE FORMED BY BETA CELLS

SECRETING INSULIN(60-70 % OF TOTAL)

1 MILLION ISLETS EACH

CONTAINING 2500 CELLS

ARTERIAL BLOOD

VENOUS BLOOD

CELL CELLSECRETORY

GRANULES

Canaliculus


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Endocrine Pancreas


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Endocrine Pancreas

Insulin

Synthesized from proinsulin

Secretion is promoted by blood

glucose

Facilitates the rate of glucose uptake

into the cells

Anabol ic hormone

Synthesis of proteins, lipids

and nucleic acids

E d i P


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Endocrine Pancreas

Glucagon

Secretion is promoted by decreased

blood glucose levels

Stimulates glycogenolysis,gluconeogenesis and lipolysis

Somatostatin (delta cells)

Regulation alpha and beta cellsecretions

PHYSIOLOGICAL ROLE OF INSULIN


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MAINTENANCE OF NORMAL PLASMA GLUCOSE LEVELS IN

SPITE OF LARGE CHANGES DUE TO FOOD INTAKE

PRESERVATION OF ENERGY STORES

STIMULATION OF GLUCOSE TRANSPORT

STIMULATION OF GLUCOSE UTILIZATION

RAPID UPTAKE OF DIETARY GLUCOSE

UTILIZATION OF DIETARY GLUCOSE

STIMULATION OF GLUCOSE OXIDATION

STIMULATION OF LIPID SYNTHESIS

STIMULATION OF GLYCOGEN SYNTHESIS

INHIBITION OF GLYCOGEN DEGRADATION

INHIBITION OF GLUCONEOGENESIS

INHIBITION OF LIPOLYSIS

INHIBITION OF PROTEOLYSIS

Endocrine Pancreas


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Endocrine Pancreas

Figure 18.19 The Regulation of Blood Glucose


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80Figure 18.19

Figure 18.19 The Regulation of Blood Glucose

Concentrations


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THE PINEAL GLAND


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Pineal Gland

Secretes only one hormone: melatonin

- involved in your circadian rhythm (your recognition of day and

night times):

melatonin secretion decreases in the day

melatonin secretion increases at night

Melatonin is also involved in longer rhythms, like monthly and

seasonal

- inhibits reproductive function

- protects against damage by free radicals

- has anti-ageing, anti-cancer effects


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The Endocrine Functions of Other

Organs

The intestines


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Produce hormones important to the

coordination of digestive activities

The kidneys


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Produce calcitriol and erythropoietin (EPO) and theenzyme rennin

Calcitriol = stimulates calcium and phosphate ion

absorption along the digestive tract

EPO stimulates red blood cell production by bonemarrow

Renin converts angiotensinogen to angiotensin I

y

Angiotensin I converted to angiotensin II in


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Stimulates adrenal production of aldosterone

Stimulates pituitary gland release of ADH

Promotes thirst Elevates blood pressure

the lungs

Endocrine Functions of the Kidneys


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Endocrine Functions of the Kidneys


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LUNGS

The heart


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Specialized muscle cells produce natriuretic

peptides when blood pressure becomes excessive

Generally oppose actions of angiotensin II

The thymus


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Produces thymosins

help develop and maintain normal

immune defenses are involved in white blood cell production

y

Adipose tissues secrete


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Leptin, a feedback control for appetite

Resistin, which reduces insulin sensitivity

p

The gonads


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g

Interstitial cells of the testes

produce testosterone Most important sex hormone

in males

In females, oocytes develop in

follicles Follicle cells produce

estrogens

After ovulation, the follicle cells

form a corpus luteum thatreleases a mixture of estrogens

and progesterone


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I fought the law, but the law won..

mechanism hormone disease (lec 3).ppt

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