•Classification of hormone

•General mechanisms of hormonal action

•Hormones of the anterior lobe

•Pituitary gland or hypophysis

•Hormones of the posterior lobe (Neurohypophysis)

The endocrine system is made up of

the endocrine glands that secrete

hormones. Although there are eight

major endocrine glands scattered

throughout the body, they are still

considered to be one system because

they have similar functions, similar

mechanisms of influence, and many

important interrelationships. Some

glands also have non-endocrine regions

that have functions other than hormone

secretion. For example, the pancreas

has a major exocrine portion that

secretes digestive enzymes and an

endocrine portion that secretes

hormones. The ovaries and testes

secrete hormones and also produce the

ova and sperm. Some organs, such as

the stomach, intestines, and heart,

produce hormones, but their primary

function is not hormone secretion.

Learn more about endocrine glands and

their hormones by selecting one of the

following topics.

Hormones are chemical substances secreted by the endocrine gland, pass to blood stream and reach other organs or tissues to exert their actions.

Or in other words:- They are chemical massengers or regulatory substances secreted by ductless glands “endocrine glands”. They are transmitted via blood stream to the various tissues and organs or which they act “target tissues”.

These gland are:-

(1)- Pituitary glands or hypothesis (2)- Thyroid gland

(3)- Parathyroid gland (4)- Pancreas (5)- Testis

(6)- Suprarenal gland (7)- Ovary (8)- Placenta

Like enzymes, hormones also function as body catalysts but they differ from enzymes in the following ways:-

(1)- Not all hormones are protein in nature.

(2)- They are formed in endocrine glands, far from their target tissues.

(3)- They are secreted in blood perior to their use. Their blood levels give indications of endocrine gland(s) activity(ies) and target tissues exposure.

*Functions of hormones:- Hormones have 3 major functions in our bodies:-

They coordinate the activities of -Integrative function:-)1(different cells in various organs of the body.

This is achieved through their effect -Regulatory function:-)2(on different metabolic processes.

Certain types of hormones -Morphological function:-)3And (control the rate & type of growth of the body.

-This gland has 3 anatomical lobes. Every lobe has its own hormones. These lobes are:-

-(a) Anterior lobe or adenohypophysis.-(b) Posterior lobe or neuro hypophysis.

-(c) Middle lobe or pars intermedia.

a- Hormones of the anterior lobe

They include:- (1)- Thyroid stimulating hormones

(2)- Adrenocorticotrophic hormones. (3)- Gonadotrophic hormones.

(4)- Growth hormones or somatotropin.

-Gonadotrophic hormones are subdivided into:*(i)- Follicle-stimulating hormones (FSH).

(ii)- Leutinizing hormones (LH) or interstitial cell-stimulating hormone(ICSH). and (ІІІ)- Lactogenic hormones or prolactin.

Growth hormone

Acts on

Bone

Thyroid stimulating hormones or Thyrotrophic

hormones

Acts on

Thyroid gland

Adrenal corticotrophichormones

Acts on

Adrenal gland

Gonadotrophic hormones

Ovary & Tests

Acts on

Follicle stimulating

hormones (FSH)Leutinizing or interstitial cell-

stimulating hormones (ICSH)

Lactogenic hormones or

prolactin

b- Hormones of the posterior lobe (Neurohypophysis)

Vasopressin Oxytocin

Increase the blood pressure Stimulate the contraction of uterus

c- Middle lobe or pars intermedia

Intermedin or melanocyte stimulating hormones (MSH)

Skin

Acts on

Release hormones (RH) & Releasing inhibiting hormones (RIH)

*-Releasing hormones:-

♦- Thyrotropin releasing hormones (TRH) .

♦- Growth hormones releasing hormones (GH-RH).

♦- Adrenocorticotrophic hormone (ACTH) releasing hormones

(ACTH-RH) or (c-) or (CRH) .

♦- Leutinizing hormones (LH) releasing hormones (LRH) and follicle

stimulating hormones (FSH) releasing hormones (FSH-RH).

♦- Melanocytes-stimulating hormones-releasing factor (MSH-RF) or

hormones (MSH-RH) *-Releasing inhibiting hormones:- ♦ GH-RIH--- growth hormones (GH)

releasing inhibiting hormone or somatostatin. Also, this factor inhibit the

release of thyroid stimulating hormone. ♦ Prolactin-releasing

inhibiting hormone (prolactin-RIH). ♦ etc…….

-In general, the endocrine system consists of a diverse group of tissues

with the common property of producing chemical substances calledhormones which regulate the metabolic activities of many tissue.

The hormones which are not only proteins but also having diverse

structures (steroid, single A.A ect.) can be classified according to their:-

(1)- Site of synthesis. (2)- Chemical nature.

(3)- Location of receptors. (4)- Nature of their signals and water

Solubility.

(1)- According of site of synthesis:- a- Endocrine hormones:- They are synthesized by one gland and transported via blood stream to the target cell (s). ex. – Growth hormones, glucan, etc.

. target tissuesThey are syntheszed near their -Paracrine hormones:-b

These hormones are rapidly catabolized before disseminating away.

ex. – Plasma polypeptides as angiotensin & kinin

c- Autocrine hormones:- These hormones effect the cells which

synthesized them. e.g – Acetyl choline, histamine and etc.

(2)- According to chemical nature:--These hormones are formed of:-:Protein hormones-(a)

(І) – Large polypeptides:- These hormones are secreted as large precursors (prohormone) and then processed to give the hormone. ex. Insulin, parathyxoid hormones, growth hormone. (ІІ)- Small polypeptides:- Antidiuretic hormone (ADH).

*- Adrenocorticotrophic hormone (ACTA). **- Oxytocin, etc.(ІІІ)- Glycoprotein hormones:- *- Follicle stimulating hormone (FSH).

**- Leutinizing hormone (LH).These hormones are derived from A. As. -:Amino acid hormones-(b)

e.g. Thyroid hormones, catecholamines from tyrosinomelanonine & sertonine from treptophan .

These hormones are derived from cholesterol. -Steroid hormones:-(c)e.g. Testosterone, progesterone, estrogens, etc.

(3)- According to receptor location & nature of signals:-

Hormones included in this group are characterized -:hormonesІGroup -(a)by:- *- All of them are lipophillic.**- All of them need transport protein Target organ (cell).***- All of them have long life span which extends from hours to days.****-All of them act on intracellular receptors inside the target cells.

*****- Their action is mediated by forming receptor-hormone complex.

ex. Steroid hormones.

Glycocorticoiod Androgens Estrogens Mineralocorticoids Progesterone etc.

Inside the cell, they interact with intracellular receptors forming hormone-receptor

complex, this complex, in turn, induce different cellular receptors. So, their action is

mediated by the formation of this complex.

Calcitral (1,25-dihydroxy cholicalciferol).

-These hormones are characterized by:-:hormonesІІGroup-(b)

*- All of them are hydrophilic. **- they reach their target cells without any transport protein. ***- Short life span (extends for minutes).

****- All of them acts on plasma membrane (extracellular) receptors.

*****- Their action is mediated by what is called second messenger as cAMP, cGMP, Ca2+ and metabolizes of phosphoinositides After reaching the target cell they bound to receptors on the outer surface of cell membrane ( plasma membrane) initiating reaction within these cells and modifying their function . cAMP= cyclic adenosine monophosphate.

cGMP= cyclic guanosine monophosphate.

******- Hormones included in this group are classified according to

their second messenger (the first messenger is the hormone itself) into:-

(І) – Second messenger is cAMP:- ex. Acetylcholine, LH, calcitonin,

glucagone, ect. (ІІ) – Second messenger is cGMP:- Arterial

natriuretic factor (ANF). (ІІІ) – Second messenger is calcium +

phosphatidyl inositides:- e.g. Acetyl choline, α-andreneric

catecholamines thyrotropin-releasing hormones, Vasopressin and gastrin.

(ІV) – Second messenger is unknown:- Insulin, prolactin and growth

hormones.

*- It is of vital importance to understand & know the general aspect of hormonal action and the mechanism of this action. **- This is how to recognize different endocrine disorders and how to aply the proper therapy.

(i) – Group І hormones:- (Hydrophobic hormones)

*- These hormones are transported by carrier proteins. *- They enter the cell by diffusing through the cell membrane.

+ [+

HRE

ReceptorHormone

Hormone-receptor complex

Hormone carrier

protein complex

Carrier

protein

*- Inside the cell, they interact with intracellular receptors forming

hormones-receptors complexes which induce different cellular responses

*- Receptor for lipophilic hormones are formed from two domains

One is responsible for binding with the hormone Is responsible for binding with a

specific DNA sequence

m-RNA

The specific protein

*- The hormone-receptor complex undergoes Temperature

Salt-dependent activation reaction

Causing

Size

Conformational

Surface-changes

}Such

receptorsOf

*-The specific DNA sequence that bind to the hormone-receptor complex

is called hormone receptor element (HRE).

*- This binding occurs only in the nucleus and cause

of a specific gene.

*-This activation and/or inactivation affect the transcription and

production of a specific protein.

*- Steroid & thyroid hormones are example of this class.

(ii)- Group ІІ hormones:- (Hydrophilic hormones)

*- They are freely transfer via blood stream to their target cell.

*- They bind with the receptors on the outer surface of cell membrane

(plasma membrane). *-Thus, they initiate reactions within these cells.

*- These reactions modify the function of these cells.

Activation

InactivationOr

orvia activationThe hormones in this group exert their actions -*

inhibition of what is called second messenger ( Hormone in this case is

the first messenger).

(i)- 3,5 cAMP as second messenger:-*- The hormones of this group exert their action by binding with a cell

membrane receptor. *- This receptor is large integral membrane

protein. *- This binding is reversible.

*- The hormone does not need to inter the cell .

*- The activated receptor activate a regulatory protein (G protein).

the effect of hormone tomediatesThis protein -*

participates in the formation of in turnActivate adenylate cyclase -*the second messenger i.e. 3, 5 cAMP.

The following items must (should) be taken in consideration to arrive at the final effect of hormonal action.

Activate

InhibitingOr

adenyl (or adenylate) cyclase.

A- G-regulatory protein:- *- this protein is named as so because it

binds guanidine nucleotides

*- This protein is consists of 3 subunits (α, β & γ-subunits).

*- only α-subunit which bind with GDP or GTP. *-

Hormone-receptor complex activates G-protein by dissociation α-subunit

from β- and γ-subunits and exchanges its GDP by GTP. *- After

exerting its effect, α-subunit (Which contain GTPase enzyme) hydrolysis

its GTP GDP

and thus,

reassociate with β- and γ-subunits and remains inactive until reactivate

again.

Guanosine diphosphate (GDF)

Guanosine triphosphate (GTF)

Phosphatase

Pi

Or

adenylate

cyclase

β

αα

β

α

β

GDP

GTP

GDP

GTP

GDP

Phosphatase

G-regulatory

protein

Pi

ReceptorReceptor ReceptorHormone+Hormone-receptor

complex

}

*- There are several types of G-protein:-

- G5 Stimulates adenylate cyclase

- G11 Inhibits adenylate cyclase

- GpLc Stimulates phosphlibase C enzyme

B- Adenylate cyclase enzyme:-

*- Adenylate cyclase is a large integral membrane protein.

*- It catalyzes the formation of cAMP from ATP.

PPi

Adenylate cyclaseN

N

NH

C

C

C

C

C

N

N

H O P O

OH

O

2P O

OH

O

P O

OH

O

H

OH

OH

H

H

H

HO

2

ATP

Adenine

Cyclic 3, 5-AMP*- Stimulation or inhibition of adenylate cyclase depends on the type of

activated G-protein by hormone-receptor complex.

*- It is (adenylate cyclase) activated by ACTN, MSH, TSH, ADH and B

adrennergic catechlamines, glucagon & calcitonin.

N

N

NH

C

C

C

C

C

N

N

H O P

O

2

OH

H

H

H

HO

2

O

*- It is inhibited by acetylcholine, α2-adrenergic amines, somatostatin &

angiotensin.

C- Protein kinase:-*- cAMP depended protein kinase is a tetramer formed of two types of

subunits 2 regulatory subunits (R )

2 catalytic subunits (C )And

Receptor Adenylate

cyclase

4 ATP

C

C

RInactivate protein kinase

Cell membrane cAMPcAMP

cAMP cAMP

+2 CActive protein

kinase

R

*- The R2C2 tetramer complex is inactive.

*- On activation by cAMP, the R2C2 tetramer complex dissociates into:-

2 catalytic subunits2 regulatory subunits, to which

4 cAMP molecules are attached

*- Active protein kinase transfers γ-phosphate group from ATP to

A specific amino acid of a specific cellular protein.

And

D- Phosphodiestrase:-

*- The level of cAMP is quickly reduced as a result of its hydrolysis by

cAMP-dependent Phosphodiestrase enzyme.

ATP 3, 5-cAMP 5-cAMP

*- Phosphodiestrase is inhibited in vitro by

Adenylate cyclase Phosphodiestrase

High concentration of methyl

xanthines (Caffeine)

Thiohpyllin Theopromine

Found in coffee, chocolate and tea

.Thus, normal consumption of such drinks give very low concentration

of methyl xanthines which dose not affect the enzyme.

(i i) – Cyclic GMP (Guanosine monophosphate) as a second

messenger:-

Cyclic 3, 5-GMPN

N

C

C

C

C

C

N

N

H O P O

OH

O

2

OH

H

H

H

HO

NH2

O

Utilization of nitrogen in the blood:-

i(Nitrogen intake) -:Nitrogen enters the body in the form of

– Protein & nucleoproteins of diet. i

i – Small amounts of nitrates & nitrites also of diet.

*- Nitrogen is present in the body either in tissues or in body fluids.

*- In tissues, nitrogen is present mainly as tissue protein.

*- In body fluids, e.g. blood, it is present in the following forms:-

(1)- Plasma proteins. (2)- Urea. (3)- Uric acid.

(4)- creatine & creatinine (5)- Glutathione. (6)- Ergothionine.

(7)- free amino acids. (8)- polypeptides. (9)- Purine and pyrimidine.

and (10)- ATP.

Nitrogen is exerted from the body by:- (Nitrogen autput)

(a)- Urine: In the form urea, uric acid, creatinine, NH3 and free amino

acids. (b)- Stool: In the form of digestive juice, shed of epithelial

cells and non digested fats (e.g. Phospholipids).

Nitrogen blance

*- It is the quantitative between nitrogen intake and nitrogen autput in

grams/day. *- If the nitrogen intake equals the nitrogen autput, a

(This condition occure in is produced. equilibriumcondition of nitrogen

the nitrogen more thanIf the nitrogen intake is -*.healthy adult)

(In this case . positive nitrogen blance is producedautput, a condition of

the nitrogen remaining in the body is used for synthesis of tissue protein.

Babies & children during their growing -*-:This conditions occure in)

periods. *- In recovery from waisting diseases. *- In pregnancy.

*- If the nitrogen intake is less than the nitrogen autput (Negative

nitrogen blance). This excess nitrogen is derived from catabolism of

tissue proteins.

-This excess nitrogen is derived from catabolism of tissue protein:

a- Waisting disease e.g. Cancer, T.B., Typhoid,………

b- Much loss of proteins from the body ( Albuminum and lactation).

C- Low protein diet and in deficiency of essential amino acids.

Hormones of the anterior lobe

1- Thyrotrophic hormone or thyroid stimulating hormone (TSH):-

Chemistry :- *- It is glycoprotein in nature containing glucosamine &

galactosamine. *- Its contains high content of cystine.

Actions:- *- Regulation of thyroid function. *- Its secretion fromthe

anterior lobe of the pituitary gland is regulated by the level of thyroxine

in blood. *- Increase of thyrixine depresses the TSH and vise versa.

Absence of TSH is accompanied by:- *- Involution of thyroid gland (Its

damage). *- Decrease of thyroid uptake of iodine.

*- Decrease of transformation of diodo-tyrosine to thyroixine.

*- Inhibition of release of thyroid hormones from the gland.

b- Adrenocorticotrophic hormones:-Chemistry:- It is a straight-chain poly peptide containing 39 A.A. residues. *- The activity of this trophic hormone is due to the first 24 A.As. *- The arrangment of A.As. in position 25-38 has no effect on its biological activity. *- This arrangment differs in different animals. Actions:- *- On adrenal cortex:- This is main action of it.*- It regulates the production of all hormones of the adrenal cortex except aldoserone (glucocorticoids, minerals-corticoids & sex hormones). *- On extra-adrenal tissues(Tissues other than adrenal cortex):- it helps the mobilization of unsaturated fatty acids (F.As.) from adipose tissues into the blood stream (plasma). Lipolysis Alcohols

*- On type of these hormones called 11-oxygenated corticostroids help the mobilization of fat to the liver by helping the release of a lipid-mobilizing hormone(Adipokinin) from the anterior lobe of pituitary. *-This hormone is differ from growth hormone and help the mobilization of fat from mesentry and omentum to the liver. *- Testosterone (exz) is necessary for mobilization of fat from the subcutaneous tissues in the fasting conditions. *- It increases ketogenesis i.e. formation of ketone bodies. *- It decreases the rate of urea formation from exogenous A.As. by increasing the transport of A.As. to extrahepatic tissues (Urea is formed only in the liver). *- it retards the loss of activity of ACTH in the liver.

F.As.

*- It possesses the MSH-activity because it is similar to it in the arrangment of the first 7 A.As. (MSH.like activity 1 %).

ACTH is controlled by:- *- Cortical hormones in the blood plasma

especially glucocorticoids. *- Substainces originated from

hepatohalamus *- Epinephrins.

c- Gonadotrophic hormones:-*- These hormones which exert important effects on the gonad.

*- These include:- 1- FSH. 2- LH. and 3- Prolactin. Their secretions are controlled by:- (i) - Levels of estrogens and androgens in blood. (ii) - Hypothalamic stimuli reacting the hypothalamus from retina, genital tracts, lips & breest.

1- FSH

Chemistry :- It is a water soluble glycoprotein containing glucose & some glucosamine. Actions :- a- In male It stimulates spermatogenesis (Formation of sperm). b- In female *- It helps growth & maturation of ovarian follides and prepare them for ovulation. *- In the presence of ICSH (LH), it stimulates the secretion of estrogen (Estrogen is responsible for the development of the female secondary sex characters, etc).

2- LH or ICSHChemistry :- It is a water soluble glycoprotein containing mannose & hexosamine Actions :- a- In male It stimulates the production of androgens (N.B. Testosterone is one of androgens which promote the growth of sex organs and is responsible for the development of

secondary sex character, etc). b- In female *- It stimulates the ovulation of mature folicle and secretion of estrogen.

*- It is necessary for the formation of corpus luteum.

*- With lactogenic hormones (prolactin), it stimulate the production of estrogen & progestrone (ovary hormones).

d- Prolactin or lactogenic hormone:-Chemistry:- It is protein in nature.

Actions:- a- In female *- It stimulate the production of milk

from mammary glands prepared by estrogen & progestrone. *- With ICSH it stimulates the corpus leuteum to secrete estrogen and progestrone. b-In male Its function is unknown.

Hormones of the posterior lobe (Neurohypophysis)

*-Hormones of the posterior lobe are:- 1- Vasopressin. 2- Oxytocin.

Chemistry:- *- Both hormones are octapeptides (Containing 8 different

A.As.). *- 3 of them are present in amide from (glycine, aspertic

acid and glutamic acid). *- Each of them contains cystine (Which is

found as 2 cysteinyl residues united with each other by a disulphide

linkage (S S). *- Therefore these hormones are sulpher

containing hormones. Glycine (NH2)

Proline

Cysteine

Aspartic acid (NH2) S

S

Glutamic acid (NH2)

Tyrosine

Cysteine

Vasopressin

Glycine (NH2)

LeucineProline

Cysteine

Aspartic acid (NH2) S

S

Glutamic acid (NH2)

Tyrosine

Cysteine

Isoleucine

Oxytocin

Calcitonin (Thyrocalcitonin):-

Structure & functions:- *- It is a peptide hormone secreted by the

parafollicular C. cell of the thyroid gland. *- It is involved in the

process of calcium regulation. *- It is composed of 32 A.As. (M.wt.

23 Kda). *- It is a calcium lowering hormone (in serum), having

metabolic effects opposite to these of para thyroid hormones. *-

Calcitonin secretion is stimulated by high plasma ionised calcium. *-

It increases the deposition of calcium in bones. (i) -

Pituitary (ii)- Thyroid (iii) –

Parathyroid hormone:- *- It is a straight-chain polypeptide.

Action:- *- On kidney helping the excretion of phosphate (phosphate

diuresis). *- Regulation of calcium & phosphorous levels in the

blood. *- On bones, helping the mobilization of calcium from bones.

Pancreatic hormones

*- The endocrine functions of the pancreas are located in the islets of

langerhans. *- Two hormones are produced by these islets they are

(Insulin & glucagon).

a- Insulin

*- It is a protein hormone, that has been isolated from pancreas and

prepared in crystalline form. *- Crystalization insulin requires Zn

& this appears to be a constituent of stored pancreatic insulin.

*- It M.wt. Is 36 Kda and is composed of Z polypeptide chaine of total

51 A.As. Content. (i) - Chain A which contains 21 A.As. and

(ii) – Chain B which contains 30 A.As.

COOHCOOH

H2N

H2N

Chain A

Chain B

S

S

S

S

S

S

1

17

7 19

20 30

21

611

*- The 2 chains are connected by 2 inter-chain disulphide bonds, the

first between A.As. no.7 of chain A and A.As. No. 7 of chain B and the

second between A.A.20 of chain A & A.A. 19 of chain B.

*- A third diulphide bond (intra) between A.A. 6 & A.A. 11 of chain A is also included. *- In the B-cells, insulin is synthesized as a precursor molecule called pro-insulin. Biosynthesis:- *- Insulin is synthesized in the polysome (site of synthesis of protein) as pre pro hormone containing 109 A.As.(M.wt.115KDa). *- In the cisternea of the rough endoplasmic reticulum, it lases 23 A.As. giving Proinsulin (86 A.As., M.wt. 90 KDa). *- Proinsulin is formed of B-chain connectiry peptide (C-peptide). *- By the action of proteolytic lysosomal enzymes, proinsulin is converted into Insulin & physiologically inactive C-peptide. *- This free, inactive C-peptide is ultimately secreted in equimolecular ratio with insulin.Mechanism of action:- *- Insulin receptor is a specific glycoprotein with which insulin bind to exert its action.*- The receptor is formed of a heterodimer, each unit of the dimer is formed of 2 subunits i.e. α, β subunits. *- The 2 units of the dimer as well as the 2 subunits are linked together by 5-3-bond giving what is called heterotetramer. *- The human receptor precursore is formed from 1382 A.As. (M.wt.190KDa). *- In the rough endoplasmic reticulum, this undergeoes cleavage to give mature human insulin receptors as a single chain peptide.

*- It undegoes extensive & raprd glycosylation in the Glogi region.

*- Removal & sialic acid & gelactose decreases both insulin binding &

action. *- Insulin receptors have t1/2 =7- 12 hours, therefor, these

receptors are in a continous state of synthesis & degradation.

Adrenal invalve adrenal cortex and adrenal medulla.

*- Adrenal medullary hormones:-

The adrenal medulla secretes Catecholamine cepinephrin

Adrenaline and nor epinepherine Noradrenalin.

Catechol amineo

(1)- Biosynthesis:- These hormones acts through 2 major types of

receptors:- (i)- α-adrenergic receptors:- These are 2 subtypes α1 – and α2

– adrenergic receptors. Through these receptors they (?) stimulate cAMP

dependent protien kinase and inhibit adenyl cyclase. (ii)- β-adrenergic

receptors:- These are also β1- and β2- receptors catecholamines through

these receptors increase cAMP.

(2)- Functions:- *- Epinephrin in general, dublicates the effects of

sympathetic nervous system. *- It is necessary to provide a rapid

physiologic response to emergencies as ColdShock

FatigueEtc.

*- In this respect, it is termed the hormone of fight or flight.

CH2

CH COOH

NH2

CH COOH

NH2

O O

OH OH

OH

O

OH

OH

O

OH

OH

CH2

( )2

NH2

CH NH2CH

2

OH

O

OH

OH

CH CH2

NHCH3

OH

Tyrosine hydroxylase DOPA decarboxylase

Dopamine

B- hydroxylase

(PNMT) phenylethanolamine N-methyl

Norepinephrine (Noradrenaline)Epinephrin (Adrenaline)

Di hydroxy phenyl alenine (DOPA) Dopamin

(1)- On the cardivascular system:- Both hormones lead to an elevation of blood presures which is more marked in cases of norepinephrine as a result of their actions on heart and blood vessels.

(2)- On the smooth muscles:- Epinephrine causes relaxation of muscles of stomach, intestine, bronchioles & urinary bladder together with contraction of sphincters.

Epinephrine elevate blood -*-carbohydrates:-(a)-Metalic effects:-)3(glucose level, since it stimulates glycogenolysis in both liver & muscles.

Epinephrine -Lipids:-(b)cAMP. -5, 3This action is mediated by -*enhances lipolysis, thus, increasing level of free fatty acids in the blood. This is due to stimulation of lipose enzyme, an action which is, also,

Catecholamines have a -Proteins:-( c)cAMP. -5, 3stimulated by little catabolic effect on protein as they enhance gluconeogenesis

(d)- Epinephrine has a direct ( in hibitory or activatory ??) effect upon

insulin release by the pancreas:- It serves as emergency hormone by:-

(i)- Rapidly providing F.As. Which are the fuel of muscles action.

(ii)- Rapidly mobilizing glucose via glycogenolyse.

(iii)- Decreasing insulin secretion, thus, preventing glucose from being

taken by peripheral tissue and keeping it for CNS actions.

They are catabolized by 2 enzymes:-

*- Active acetate (Acetyl Co A) is the precursor of all stroid hormones.

*- At gives chlesterol which is converted to pregnenolone.

*- Pregnenolone (A) either is converted to 17-hydroxy pregnenol (C )

which give dehydro epiandroserone (D) or progestrone (B). *- Thus

pregnenolone (A) and ( C) are converted to a variety of active hormones

which require dehydrogenases--(b)and oxygences--(a)by spicific

molecular oxygen (in case of (a) and NADP in case of (b).

*- Generally, the results of these enzymatic reactions is the addition of

21or C17, C11at CKetonic groups–(ii)or groupsHydroxyl–(i)

positions. *- In general, C21 hydroxylation is necessary for both

glucocorticoids & mineralocorticoids.

They are catabolized in the liver by:- (i)- Reduction of the double bond

in the stroid nucleus. (ii)- Reduction of the ketonic yp at C3 .

*- The producted metabolites become conjugated with either:-

(i)- Glucaronic acid (major pathway). (ii)- Sulphated (minor pathway.OR

*- Most of these metabolites are excreted in bile, however only 20% are

excreted in stool. *- The rest (80%) becomes re-absorbed and 70%

(of 80%) are excreted in urine and 10% (of 80%) in sweet the remaining

20% of the absorbed 80% are still circulating in the blood.

(A)- glucocorticoids

*- The steroids containing OH or C O at C11 position and OH at C17

have glucocorticoid activities e.g. Corticosterone, hydrocortisone

(cortisol), 11-dehydrocorticosterone & cortisone.

*- The most important glucocorticoids are cortisol and corticosterone.

*- They act as steroid hormones by modification of RNA and enzyme

synthesis in the target tissues. *- The are lipophilic hormones

- (t1/2 = ? High ( ? Days). - Need carrier.

- Intra or inter cellular receptors. - Their action is mediated by ??

*- They control carbohydrate, lipid & protein metabolism:-

a- On carbohydrates:- *- They decrease glucose uptake by the

inhibition of glucokinase enzyme hyperglycomia.

*- They activate inhibit glycolysis. *- They help gluconeogenesis, sine the activities of the enzymes which are involved in amino acids conversion into glucose are increased or decreased (??).

*- The glycogen deposition is increased or decreased (??) (The rate of glycogen formation is not sufficient to control the glucose level). (In general, the action of glucocorticoids are metabolcally antagonistic to insulin with a consequent rise in blood glucose level i.e. hyperglyccemiais developed).

b- On lipids:- *- Glucocorticoids enhance lipolysis (break down of triglycerides (T.G.) of adipose tissues particulary in the extremeties ). Thus, the levels of free fatty acids (FFAs) are increased in the blood.

*- They help gluconeogenesis from the liberated glycerol and of hydrolysis of triglycerides (TG).

c- On protein metabolism:- *- In physiological concentrations,

glucocorticoids have anabolic effects. *- Deviation from normality

leads to catabolic effects (hypersecretion). *- In the latter case protein synthesis is decreased, wherees protein metabolism is increased.

*- This leads to increased (decreased) excretion of non-protein (NPN) compounds in urine and a state of negative nitrogen balance is developed

d- Other effects of glucocortioids:-

As they used in the treatment of -inflammatory effects:-Anti-(i)collagen diseases as rbeumatoid arthritis.

Cortsol decreases the immune -Immune supressive effects:-(ii)response associated with infection and allergic states.

Glucocorticoids are elevated several folds in response -Stress:-(iii)to a cute stress to reverse the decreased blood presure resulting from emotional or surgical shock.

They increase lung surfactants, -*-Miscellaneous effects:-(iv)consequently, they are used in the treatment of respiratory distress

syndrome (RDS) in newly born premature infants. *- They stimulate the secretory functions of gastro-intestinal tract (GIT): e.g. increasing the

secretion of HCL, pepsinogen and trypsinogen etc. *- Administration of glucocoticoids, thus, enhances GIT ulceration e.g. (peptic ulcer).

(B)- Mineralocorticoids*- The most potent mineralocorticoid is aldosterone. *- Its pathway

of synthesis needs C17 hydroxylation. *- With exception of androgens, all coticoids increase the absorption of Na+ & Cl- by the

renal tubules (i.e. reduce Na+ & Cl- excretion). *- However, glucocorticoids e.g. cortisol have the least sodium retaining action while

aldosterone is at least 1000 times as effective as cortisol in this respect.

# Mineralocorticoids have the following actions:-

(1)- Na+ retaining actions via:- (a)- Reabsorption of Na+ & Cl- is

enhanced (or decreased ?) by renal tubules. (b)- Their excretion ( ? )

is also reduced by : (i)- Sweet. & (ii)- GIT.

#

Disturbances of adrenal functions:-

(a)- Disorder of glucocoticoids: (Hypofunction)

-Adrenal insufficiency (Adison disease as an example):-(i)

*-It is characterized by: 1- Hypoglycemia. 2- Extreme sensitivity

to insulin. 3- Intolerance of stress. 4- severe weakness & nausea.

5- weight loss.

*- This pateint suffer from low blood pressure & decreased glomerular

filtration rate and ability to excrete H2O.

*- Low plasma Na+ (with increased K+), easinophils and lymphocytes.

*- Hyperpegmentation of skin & mucus membranes occurs due to

compensatory increase in ACTH (has a similarity of MSH as was

previosely reported) secretion (why ???).

C- Sex hormones*-The tests&ovaries in addition to their function in providing spermatory or ova synthesize also sex hormones.

(1)- Male sex hormones

*- The princepal male sex hormone is testosterone. *- it is synthesized,

mainly, by the leding cells of the tests. *- In addition, androstenedione

& dehydroepiandrosterone are also produced. *- The major adrenal androgen, dehydroepiandrosterone is produced by side chain cleavage of 17-hydroxy-pregnenolone.

# - Metabolic actions:- *- They have protein anabolic effects, thus

producing a state of ? Nitrigen balance. *- Androgens promote protein synthesis in male accessoy glands, thus, growth & functions of epididymis, vas deference prostate, seminal vesicles and penis are

enhanced. *- In general, they are responsible for male secondary sex

characters. *- Excretion of 17-ketostroids in urine, is in part snsidered

to be a reflection of testicular hormonal production. *- This tests (measurement of 17-retostroid level) contribute to 1/3 of the total urine

ketostroids. *-In norml children (male or female) up to 8th year of life there is a gradual increase in 17-ketostroids excretion with no sex differences.

CH

OH

O3

OHCH

O

O3

OH

OH

OH

(i) Dehydrogenase

(ii) Isomerase

17-hydroxy-pregneolone 17-hydroxyprogester

Lyases Lyases

OH

O

O

O

Dehydrogenase

Dehydroepianderosterone Anderstendione

Androstendiol

O

OH

Testosterone

Dehydrogenase

Hydrogenase Hydrogenase

*-After puberty, males show higher 17-ketostroids excretion than

females.

(2)- Female sex hormones

*- The 2 main types of female sex hormones are produced by the ovary.

*- These 2 types of hormones include the folliculer (or strogenic) hormones

which are produced by cells of graffian follicules and progestronal

hormones (which are derived from corpus leuteum that is formed in the

ovary from ruptured follicule). *- Small amounts of adrenal oestrogen

are produced from testosteron either from dehydro epiandrosterone or

from 17-hydroxyprogestrone.

(i)- Follicular hormones:- *-They are C18 stroids differing from

androgens in lacking methyl group at C 19 . *- In contrast to all other

stroids, ring A is aromatic. *- The most active hormone in the

circulation of all estrogens is oestradoil (E2). *- E2 is a

metabolic equilibrium with oestrone (E1). *- Estratriol (E3) is the

principal oestrogen found in urine of pregnant women.

*- E3 is produced from estron (E1) by its hydroxylation at C16.

O

O

O

OH

OH

OH

OH

O

OH

OH

O O

OH

Estriol (E3)

Urine of pregnency womem

Esrone (E1) Estradiol (E2)

Androstene dione Tetosterone

Aromatase Aromatase

Hydroxylation

# -Functions:- *- Follicular hormones prepare the uterine mucoses

for latter action of progestational hormones. *- These actions

include proliferation of the endometrium depening of glands, increased

vascularity, etc. *- All these changes begin after cessation of

menstral bleeding. *- They maintain female secondary sex characters

acting against (antagonistic) testosterone.

(ii)- Progestrone hormone:- *- It is the hormone of corpus leuteum.

*- It is also formed by adrenal cortex and placenta.

CH

OH

O3

CH

O

O3

CH

OH

O3

CH H

H

Pregnendone Progestrone pregnandiol

# -Functions:- *- This hormones appears after ovulation and

causes extensive development of endometrium, thus preparing the uterus

for reception of embryo, and for its nutrition. *- Progestrone also

stimulates growth of the mamary glands. *- When pregnency

occure, corpus leuteum is maintained, and menstruation and ovulation

are suspended. *- the concentration of progesterone decreases near

term. *- Progesterone has anti estrogenic effect on myometrium.

--It decreases excitability & sensitivity of uterus to oxytocin

throughout pregnency.