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بسم ( االرحمن االرحيیم

Quick revision

Yesterday we talked about types of the receptors ; iontropic , metatropic , tyrosine kinases and other receptors .

Lipid-soluble receptor are either nuclear or cytoplasmic receptors . And this kind of receptors lead to transcription of genes through binding to hormone –responsive complex ( hormone-responsive element ).

This transcription leads to formation of proteins , this protein may be an enzyme , transporter , channels , so on…., and that affect cellular metabolism . Doctors mentioned short summary about the last lecture , and it`s the same .

The carriers for these lipid soluble hormone are either specific or ***

.specific-non

Specific carriers form from the cell usually nearby the cells that secret them .

Nonspecific carriers means they can carry any hormone .

The specific carriers for **

Thyroxin is thyroxin binding globulin For steroids is steroid –binding globulin Sex hormones is sex hormones-binding globulin

Non-specific **

Albumin ( protein ) for steroids Prealbumin ( transthyretin )

U know that the hormone concentration stay almost constant ,that's called hemostatis , and the regulation of this hormone concentration is by negative feedback mechanism .

the hardest thing in life is to know which bridge to cross ,,,,,

& which to burn ^_^

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If the concentration of hormone from target cell decreases , leads to negative feedback of stimulus .

Like thyroxin , thyroxin produced from thyroid glands under the effect ( stimulation of TSH ) ( thyroid –stimulating hormone ) from the pituitary .

If the thyroxin increases , they goes negative feedback on the hypothalamus and pituitary , decreasing the secretion of TRH ( from hypothalamus) and TSH from pituitary.

If thyroxin decreases, they goes negative feedback on the pituitary and hypothalamus , increases TRH , TSH .

This is most of hormones goes under negative feedback mechanism where the response is opposite to the stimulus , the stimulus is increasing , response is decreasing; the stimulus decreases, response increases .

If you have hyperthyroidism means that if you measure T3 & T4 in a blood , u find it`s high . the source of high levels of T3 & T4 in a blood could be the pituitary or the thyroid .

How do u know the source is pitutarory or

thyroid ? U measure TSH , if TSH is high , and T3 & T4 are high , the source is pituitary why, & why this is abnormal ? because the pituitary releases TSH uncontrollable ( without control ) , that means it doesn`t have negative feedback for T3 & T4 . T3 & T4 are high , TSH is high , the source is pituitary

why ?. re high , but TSH is low , the source is thyroid If T3 & T4 a

Because thyroid ( when it`s abnormal ) secreting T3 & T4 uncontrollable , it will go feedback on pituitary , decrease TSH ( negative feedback ).

roof that you are trying ;) (((mistakes are p )))

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***********************************************************

backdPositive fee

Stimulus and response are in the same direction . Some hormones are secreting by positive feedback like oxytocin , LH during ovulation , stimulus is estrogen ( high level ) , leads to high level of response LH It's called positive feedback , it's for sometimes not always .

Plz refer to photo below

this kind of receptors u remember when we talked about lipid _soluble substrate and this work on DNA system leads to transcription of genes.

Membranous receptors like substance or hormone leptin-binding receptor , leptin substance is hormone or peptide that secret from lipid source that it's important in satiation and hunger state and any type like obesity, fatness , increasing in weight.

leptin binds to its receptor on the membrane, the membranous receptor its self it's a kinase but a different kinase ,so it's called just another kinase( janus kinase ) (JAK) .

once the leptin binds to the extra cellular part of the receptor (that bind the hormone or protein) , it phosphyrates this kinase , the kinase is auto

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phosphorylated , when the kinase is auto phosphorylated ,it goes to phosphorylate some intracellular substrate .

ansducer and activator (signal tr 3stat here is substrate these intracellular

of transcription )..

tein ro) and p transcription(gene inside goes to gene systemstat formation; the proteins could be any thing, could be enzymes ,channels ,any thing … this kinase may phosphyrate enzymes intracellular.

phsophyration and dephsophyratation the enzymes, may change to physiological effects .

goes to gene transcription or phosphyrate statphsophylogical effects by

enzymes intracellular.

through or statit is either phosphyrate intracellular receptor like JaKactivating enzymes by JAK directly , lead to physiological changes: Could be change in metabolism , formation of protein channels , formation of protein.

signal transducer like second messenger

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Tyrosine kinase

Tyrosine is amino acid that is phyosphyrted at tyrosine phyosphratase domain .

When jak phosphyrate it goes to physophyrate intracellular receptors and these intracellural receptors work like second messenger.

.The receptors could be tyrosine phosphatase or tyrosine kinase

Tyrosine kinase

.e , this kind is specific for insulin makes phosphyrat

The receptor usually have two subunits , that expose outside ,some times called α subunits and β subunits and integral proteins subunits called β subunits .

When binds to hormone it leads to phosphyrate the tyrosine kinase so we

. ionautophosphyratcalled it

Once tyrosine kinase phsophyrated , it goes to phosphyrate intracellular receptors (substrate) then we have an action.

:Trosine kinase for insulin Insulin receptors consists of two α and β subunits . These receptors dimerize when bind to insulin Insulin bind to ligand sites on plasma membrane and activte it , leading to auto physophryation of tyrosine kinase , activates tyrosine kinase , and this lead to activate signal molecules.

Tyrosine phosphatase

:Its means dephosphyrate enzymes or intracellural substance. Tyrosine

kinase Makes

phosphyration

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:signal molecule intracellular Activating of Has the action of stimulating fat , protein , glycogen synthesis , glucose transport

ü : when it go to membrane ,lead to enter glucose Glucose transport

by diffusion through the membrane or facilitated diffusion.

ü fat , that lead to protein , is stimulating enzymesAction of insulin glucose synthesis , or stimulate channels

ü Stimulate substrates that lead to transcripition of genes to make

proteins , these proteins go to membrane channels for glucose ( insertion of GLUT-alfa carrier protein ) , make glucose enter the cell.

Insulin action make hypoglycemia ( make the glucose enter the cell , by increase the number of channels ) Insulin binds to α subunit leads to autophosphyrate tyrosine kinase. Once autophosphyrates tyrosine kinase, kinase leads to physophyrate intracellular insulin-receptor substrates, Cause the affect of insulin.

It's differ from other

receptors because it don't need

second messenger

like cAMP , Ca+2

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in synthesis , Glucose transport , stimulate enzymes that stimulate prote

fat synthesis , glycogen synthesis

Insulin binds to α subunit causing autophosphyrate of β receptors (β receptors its self has the tyrosine kinase activity , but it's not active unless it autophosphyrates.

Once the insulin receptors substrates phosphyrated ( not one but many of them )One of them may go to the channel , the most important channel

potassium channel it'shere

Because the membrane is polarized , Once the potassium channel is

, it ochemical gradienttotal electr opened , potassium will move withwill move with electro gradient and against chemical gradient . That why giving insulin decrease potassium concentration in plasma . And That's why must be careful when u deal with person takes insulin , so you need to calculate potassium level regularly. Because if there are lacking of potassium it's very dangerous to the heart

) miaealkhypo of( because ic arrthymiscausing card

( be careful not potassiumrefers to miaealkhypoand miaealkHyper

refer to calcium )

sodiumand refers to hyponatremiand a miaeHypernatr Membrane signal may open potassium channels , may go through transcription of genes ( mutagenic signal , mutagenic developing of mitosis or division ),,,They go to the genes and formation of transporter that insert to membrane, make glucose influx .

May make either phosphyration or dephosphyration .

most of the problems in life are because two reason : we act without thinking ,,,,, or we keep thinking without acting ^__^

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TSH ____ > THYROID STIMULATING HORMONE ,***

is a glycoprotein hormone.** Glycoprotein : FSH, LH , TSH , HCG **

Consist of two subunit α and β subunits. ** Alfa subunit is common. **

**All of glycoprotein have the same alfa subunit , but beta subunit is specific .

**TSH is secreting from anterior pituitary under the affect of TRH ( from hypothalamus) , and it activates G protein ,and go under the same second – messenger mechanism Like CAMP second messenger mechanism and phosphyrate kinase A It bind to its receptor on the membrane , it doesn’t pass through the membrane .

Plz refer to slides

specifity is glycoprotein , bind to beta subunit of its receptors ( hasLH for LH ).

( gondtropin releaing hormone ) is a peptide hormone , it`s GnRH

released from the hypothalamus , and it binds to its receptors on the anterior pituitary .

SO it's very close to pituitary , why that's important ???

. diluteirculate in blood and c GnRHTo prevent

from the LH & FSH of releasingThis hormone is responsible for pituitary .

TO STOP CAMP second messenger mechanism by activation of phosphdiesterase , ___convert CAMP TO AMP

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linked receptor and links to phospholipae –receptor is a enzyme GnRHC which converts PIP2 to IP3 & DAG IP3 goes to endoplasmic reticulum causes Ca+2 releasing , which go to kinase C AND activate it .

Kinase C is responsible for release LH & FSH from the pituitary. LH & FSH is gonadtropin proteins that they act on the gonads (testis in male and ovary in female).

ptide ))GUANYLYL CYCLASE ( ANP (atremnpe gyanylyaseIts receptor is membranous receptor , in this case it link to

ANP ( atrial natriuretic peptide ***( .GMPc to GTPwhich convert cyclaereceptor )

Serine , threonine kinase ( TGF ) It is for amino acids (it's different from tyrosine kinase ) , it's membranous receptor for peptides , and it's autophosphyrated , it's called TGF ( transforming growth factor )

***Doctor said that not all growth factors are peptide , he said: I think all of them are peptides !!!!

Summary

Signaling molecule ( hormone ) binds to its receptor of target cell and inside the cell it has second messengers , and through the formation of second messengers , u have biological effect . this called signal transduction : is the conversion of signal into other action inside the cell substrate .

Signaling molecule

(hormes)

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;Third messenger *** the substrate which translocates from the cytoplasm to nucleus , or from the nucleus to cytoplasm .

In insulin binding mechanism , stat is the second messenger or insulin substrate , it go inside the nucleus and from the nucleus it forms substrate or protein that called third messenger .

in slide num 36 and add that : scheme the Doctor just read

v Protein and peptide `s receptors are membranous receptors .

v Styroid hormones , thyroxine , VD3 are lipid-soluble hormone .

v Lipid soluble vitamins are A,E,D,K and they bind to its intracellular receptor . .

*************************************************** u will never be (brave) if u don't get (hurt)... u will never (learn) if u don't make (mistake)... u will never be (successful) if u don't encounter (failure)...

I tried to write the best ,,,

Receptor of target cell

Intracellular molecule (second messengers)

biological effect

Signal transduction

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it was a hardest lecture but for you everything is easy my family ,,,, please forgive me for any mistake here ,,, I wish to you from my heart all the best

Your sister: - Done By

Maria Black Abu Naseir

**Special thanks to my sister Ghaida'a Al-Qallab