Hormones Reviewer

8/9/2019 Hormones Reviewer

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HORMONESHORMONE

(POST. PITUITARY)SOURCE STIMULI EFFECTS ON ORGANS SPECIAL TRAITS CLASSIFIC. PATHO -

PHYSIOLOGY1. Vasopressin(ADH)

Post. Pituitary

*Supraopticnucleus &Paraventricular nucleus(Hypothalamus)

*Transported byNeurophysins I

*Stored in thePosterior Pituitary(Neurohypo-physis)

*Release-increasedosmolality of plasmaOsmorecep-

tors (hypoth.)Barorecep.(heart)

*Renal Medulla cells –increased permeability- osmotic equilib. Of collecting tubule urine w/hyportonic interstitium

*Vasoconstriction in vascular beds (+ peripheralresistance)*Water reabsorption (luminalmembrane of epith. Cells of cortical & medullarysegments kidney collectingducts)

*Nonapeptide w/ cysteine atposition 1 & 6 linked bydisulfide (S-S) bridge

*Arginine at posit. 8 – AVP

*Oligopeptide*Hydrophilic*Extracellular receptor –Ca/PI

DIABETESINSIPIDUSa.1* DiabetesInsipidus or PDI (-ADH)

b. HereditaryNephrogenicDiabetes Insipidus(receptor defect)

SIADH – dilutionalhyponatremia w/secretion of hypertonic urine

2. Oxytocin

Post. Pituitary

*Supraopticnucleus &Paraventricular

nucleus(Hypothalamus)

*Transported byNeurophysins II

*Stored in thePosterior Pituitary(Neurohypo-physis)

Release*Neuralimpulses from

nipplestimulation*Vaginal &uterinedistention

Production*Stimulated –estrogen*inhibited -Progesterone

*Nonapeptide w/ cysteine atposition 1 & 6 linked bydisulfide (S-S) bridge

*Impt. Chem. Grps:-1* amino grp of aminoterminal cys-phenolic grp of tyr -carboxyamide of asparagines, glutamine &glycinamide-disulfide grp

*(+) milk ejection*(+) uterine smooth musclecontraction at birth

*Oligopeptide*Hydrophilic*Extracellular

receptor –Ca/PI

HORMONE

(ANT. PITUITARY)

SOURCE STIMULI EFFECTS ON ORGANS SPECIAL TRAITS CLASSIFIC. PATHO -

PHYSIOLOGY3. Growth Hormone(GH)

Ant. Pituitary

*see table p14 for factors affectingsecretion

*Ant. Pituitary –somatotrophcells

*sleep*stress,*exercise*severehypoglycemia*elevatedamino acidlevels*anesthesia*balance b/wGHRH &

GHRIH

*Protein synthesis (+)*Carbohydrate metabolism(anti-insulin effects)*Lipid metabolism

*Mineral metabolism*Prolactin-like effects

*see p. 14

*Polupeptide composed of asingle chain of 191 aminoacids w/ 2 intramolecular disulfide bonds

*structurally related to HumanChrorionicSomatomammotropin(placenta) – stimulatesgrowth of developing fetus

*protein*Hydrophilic*Extracellular receptor –Kinase or Phosphatasecascade

*DWARFISM – ( - )secretion

*GIGANTISM –(+) secretion

*ACROMEGALY –excessive GHrelease

/acdg 1



HORMONE(ANT. PITUITARY)

SOURCE STIMULI EFFECTS ON ORGANS SPECIAL TRAITS CLASSIFIC. PATHO -PHYSIOLOGY

4. Prolactin(PRL, Lactogenic H.,Mammotropin H.,Luteotrophic H)

*lactotrophs of Ant. Pituitary

*Bipolar PRH(TRH, VIP,Serotonin) &PRIH(dopamine) –to portal blood

by hypoth.neurons –receptors onlactotrophs –inhibits

*Initiation * maintenance of lactation

*Induce synthesis of milkproteins (lactalbumin &casein)

*Males – increasedphysiologic levels; maintainconcent. Of LH receptors onLeydig cell membrane intestis = sustain normaltestosterone production

*199 amino acid residues*3 internal disulfide bridges*Secreted episodically (24-hr patter release) – nocturnalpeak related to sleep

*Protein*Hydrophilic*Extracellular receptor –kinase or phosphatase

cascade

*PROLACTIN-SECRETINGTUMORS= Amenorrhea(cessation of menses)

=galactorrhea (milkdischarge)=gynecomastia &impotence in men

5. ChorionicSomatomammotropin(CS, Placental

Lactogen)

*No definite fxn*Lactogenic * luteotropicactivity & metabolic effects

similar to GH

*Protein*Hydrophilic*kinase/phos-

phatase c.6. ThyroidStimulating Hormone(TSH)- Thyrotropin

*Thyrotrophs -cells in the Ant.Pituitary*Receptors –epithelial cellsin the thyroidgland

*CONTROL- TRH – from

hypothalamicneurons intohypoth.-hypophysealportal blood-Receptors –thyrotrophs inthe ant.pituitary of TSH

-inhibition –high bloodlevels of thyroidhormones(neg. feedbackloop)

*Stimulates thyroid tosynthesize & release thyroidhormones

* acute (mins)+ TRH =+ TSH = + T3, T4

*chronic (days)+ protein, phospholipid,nucleic acid synthesis+ size & # of thyroid cells

*Glycoprotein composed of 2subunits-alpha – also in FSH, LHPHCG (primates)-beta – receptor specificity

*Glycoprotein*Hydrophilic*Extracellular receptor –cAMP

7. Luteneizing (LH *Gonadotrophsof Ant. Pituitary

*Main regulator – GnRH/LHRH

*Corpus luteum cells &Testosterone (Interstitialcells of Leydig) = +production of

*Gonadotropins bec.Stimulate the gonads*Not necessary for life but

*Glycoprotein*Hydrophilic*Extracellular receptor –Camp

*HYPOGONADISM – ( - ) secretion of LH or FSH = failure

/acdg 2



HORMONE SOURCE STIMULI EFFECTS ON ORGANS SPECIAL TRAITS CLASSIFIC. PATHO -PHYSIOLOGY

*Sex steroidsinhibit secretionof this & havedirect neg.effects ongonadotrophs

*Neg. feedbackloop – pulsatilesecretion of LH, FSH.

progesterone*Males – secretion of testosteroneFemales – Thecacells(ovary) respond to LHby Teststerone, converted to

estrogen by AdjacentGranulosa cells- Preovulatory LH surge =ovulation of mature follicles

essential for reproduction*Large glycoproteins with 2subunits-alpha –same-beta – unique to ownreceptor

in gonadal fxnM: abnormal sperm#sF: cessation of reproductive cycles

*Excess secretion –due to gonadalfailure or pituitarytumors = nobiological effect8. Follicle-Simulating

Hormone (FSH)*Gonadotrophsof Ant. Pituitary

*Males – sperm production- supports fxn of Sertoli

cells*Females – stimulatesmaturation of ovarianfollicles

*Glycoprotein*Hydrophilic*Extracellular receptor –cAMP

9. ChorionicGonadotropin (CG)

*Syncytiotropo-blast of

placenta

*Increase blood & urine after implantation (basis of

pregnancy tests)

*Glycoprotein*Hydrophilic

*ER–cAMP10. Adrenocortico-tropin Hormone(ACTH or Corticotropin)

*Synthesis –Corticotrophiccells of Ant. Pit.

CONTROL*CRH (hypoth)

– secreted inresponse tostress as“stressmanagement”of glucocorticoids

* + synthesis & secretion of Adrenocortical steroids:Glucocorticoids (cortisol,little aldosterone)

*Regulates growth & fxn of ADRENAL CORTEX

*Adrenal Steroid synthesis &release by enhancingcholesterol conversion to

PRENENOLONE

*Single polypeptide consistingof 39 a.a. – 24 amino terminalresidues required for fullbiologic activity

*Polypeptide*Hydrophilic*ER–cAMP

*CUSHING’SSYNDROME – x’sproduction of ACTHby pituitary or ectopic tumor

*see manifestationsp. 19

11. β – Lipotropin(β-LPH)

*Lipolysis & fatty acidmobilization

*Carboxyl terminal 91 a.a. of POMC*only β-LPH & its cleavageproducts γ-LPH & β-endorphins in human pituitary

*Polypeptide*Hydrophilic*ER–cAMP

12. Endorphins *Carboxyl terminal 31 a.a.residues of β-LPH8Removal of 15 & 14 a.a.from carboxyl terminal end =γ & α endorphins*acetylated, inactive in the

pituitary/acdg 3



*bind to opiate receptors(CNS) – endogenous controlof pain perception

HORMONE SOURCE STIMULI EFFECTS ON ORGANS SPECIAL TRAITS CLASSIFIC. PATHO -PHYSIOLOGY

13.Melanocyte-Stimulating Hormone(MSH0

*StimulatesMELANOGENESIS bycausing dispersion of

intracellular granulesresulting in darkening of skin

*Contained within POMCmolecule but not in post-natalhumans

*Actual circulating MSHcontained w/in larger γ or β-LPH

*ADDISON’SDISEASE –Concomitant

secretion of γ & β-LPH = insufficientproduction of glucocorticoids,hyperpigmentaiondue to + plasmaMSH activity

HORMONEReg. fuel metab.


1. Insulin *See p. 21 for synthesis*proinsulin &

insulin bothcombine withZn to formHexamers.

*Increase inplasma glucoseconc.

*β-Adrenergicagonists - +cAMP

*α-Adrenergicagonists(epinephrine)(-)

*chronicexposure to

xsv levels of GH, Cortisol,Placentallactogen,estrogens, &progestins

*Pharmacolo-gic agents(sulfonylureas,tolbutamide)

*mech of action

*Membrane transport--adipose cells – recruitmentof glucose transporters

--hepatocytes – indirectlyenhances influx byphosphorylating glucose

*Glucose utilization--Increase hepatic glycolysis--entry of glucose in skeletalmuscles--increase hexokinase IIactivity = glucosemetabolism--adipose cells – anabolic;

lipogenesis--liver & muscle –glycogenesis

*Glucose production(Gluconeogenesis)--decrease PEPCK=inhibitgluconeogenesis

*Glucose metabolism--decrease blood glucoselevels

*polypeptide (5.73 kDa) w/ 2chains (A – 21aa & B – 30aa) linked by 2 inter &

intrachain disulfide bridges*Interchain Disulfide bondsA7–B7, A20—B19*Intrachain disulfide bondsA6—A11

*conserved positions (activeregions)--3 disulfide bonds--hydrophobic residues incarboxyl terminal regions, Bchain

--amino & carboxyl terminals,A chain

*Hign in Zn in B cells,complexes w/ insulin;precursor, Proinsulin

*Plasma half-life less than3-5 mins

Metabolized:a. Insulin-specific protease(liver, kidney, placenta)

DIABETESMELLITUSa. NIDDM; Type II

b. IDDM; Type I

/acdg 4



p.23 *Lipid metabolism--inhibits lipolysis (liver,adipose tissue)--inhibits hormone-sensitivelipase = decrease in circ.

b. Hepatic glutathione-insulintranshydrogenase (reducedisulfide bonds)



Free fatty acids

*Protein metabolism--anabolic effect byenhancing protein synthesis& retarding degradation--stimulates uptake of neutral aa in muscle

2. Insulin-relatedpeptides

Relaxin & insulin-likeGF (I & II)

*homologous B & A chains atthe amino & carboxylterminals of precursor molecule joined byconnecting segment

3. Glucagon *Synthesized asProglucagon*proteolyticallyprocessed =glucagons w/inα cells of pancreatic islets

*low bloodconc of glucose(hypoglycemia)

*elevated bloodlevels of aa=convert x’s aato glucose byenhancinggluconeogene-sis

*exercise –glucagonssecretion dueto glucosedepletion

*most potent gluconeogenichormone--rapid mobilization of potential energy sources intoglucose by glycogenolysis--stimulates breakdown of glycogen in liver --increased production of glucose in liver = increasedplasma glucose conc

*stimulates lipolysis

*single polypeptide 29 aa*to maintain normal conc. of glucose in blood (oppositeeffect of insulin –Contrainsular)

*half-life (5mins)*inactivation in liver =enzyme. cleavage in Ser 2 &glutamine 3, removing 1 st 2aa from amino terminal end

4. Somatostatin *synthesized inD cells of Pancreaticpolypeptide:Formsa. SS-14 &b. SS-28--from

*Pituitary gland – (-) GH*Pancreas – paracrine; (-)insulin & glucagons-suppress exocrinesecretions*GIT – (-) gastrin,cholecystokinin, secretin,vasoactive intestinal peptide

*2 cys residues in ss-14 allowpeptide to form internaldisulfide bond

/acdg 5



proteolyticcleavage of preprosomatos-tatin

*Nervous system –neuromodulatory activity



5. Thyroid hormone

--Thyroxine (T4)--Triiodotyronine (T3)

* Thyroglobulin

(thyroidepithelial cells) – secreted tolumen of follicle

*Thyroidperoxidase(fabrication of thyroid horm.)a. Iodination of tyr onthyroglobulin/

organification of iodideb. Synthesis of T3/T4 from 2iodotyrosines

*see p25

CONTROL

*TSHa. synthesis of iodinetransporter b. thyroidperoxidasec. thyroglobulin

--rate of endocytosis of colloid (highTSH = faster)

*Metabolism

--increase basal metabolicratea. Lipid – fatmobilization=inc conc of FAin plasma--oxidation of FA--(-)TH level=+blood cholesconc

b. Carbohydrate--enhance insulin-dependententry of glucose in cells

--increase gluconeogenesis& glycogenolysis--increase sensitivity of Bcells of pancreas = optimalinsulin secretion

*Growth – growth retardationin thyroid deficiency

*Dev’t – fetal & neonatalbrain

*Cardiovasc. System - +heart rate, cardiaccontractility, cardiac output--vasodilation=+blood flow

*CNS – (-) mentallysluggish; + anxiety &nervousness

*Reproduc. Sys – hypothy. =infertility

*Derivatives of tyrosine bound

covalently to iodine*T4 plasma half-life (7days)*T3 plasma half-life (1-1.5days)

*poorly soluble in water *99% bound to carrier proteinin blood

CARRIERS (maintenance of pool):a. Thyroxine-binding globulin

(liver)b. Transthyreinc. Albumin

HYPOTHYROIDISM

Causes:a. Iodine deficiency(goiter)b. destroyed partsdue to inflammation= 1* ThyroidDisease--Myxedema – fromearly childhood ---CRETINISM(irreversible growth& mentalretardation)

HYPERTHYROIDISM-oversecretion--GRAVE’SDISEASE(autoantibodiesbind to & activateTSHreceptor=continualstimulation of Thyroid Hormonesynthesis)

6. CatecholaminesEpinephrine &

Synthesis:a. Sympathetic

Control*ACH from

* + rate& force of contractionof heart muscle

*Bind loosely to & are carriedin circulation by ALBUMIN &

/acdg 6



Norepinephrine neuronsb. adrenalmedullac. CNS

*see p28

preganglionicsympatheticfibersinnervatingmedulla

*”stresses” –exercise,

hypoglycemia,trauma

* + metabolic rate*constriction of bloodvessels (norepinephrine)*dilation of bronchioles*dilation of pupils*stimulation of lipolysis in fatcells*inhibition of certain “non-

essential” processes (GIsec. & motor activity)

other serum proteins

HORMONEAffect Ca Levels


1. ParathyroidHormone

*Cells of Parathyroidglands

*synthesized asPreprohormonePreproPTH – 1*

gene productProPTH –amino terminalhighly basichexapeptideextension

*Fates fromGolgi App:a. Transportinto a storagepoolb. degradation*(+Ca= -degradation)c. immediatesecretion

*low cellular conc of free Ca*changes inbloodphosphateconc (indirect)

*Calcium Homeostasis-restores normal ECF Ca2+conc by resorption frombone & kidney, Calcitrolsynthesis (diet, intestine)

*Phosphate homeostasis

-release of phosphate w/Ca2+ during bonedemineralization.-increase renal phosphateclearance

** increase ECF Ca2+ &decrease ECF phosphateconc

*most impt endocrineregulator of Ca &phosphorous conc in extracellfluid

*85 aa peptide (9.5 kda) w/oCHO

*PTH 1-34 = full biologicactivity

*Receptor binding – residues25-34

*PTH secretion is inverselyrelated to amt of ambientconc of ionized Ca2+ & Mg2+

HYPOPARATHY-ROIDISM-insufficient PTH w/(-)ionized Ca & +serum phosphatelevels*damage during

neck surgery (2*hypoparathyroid.)*Autoimmunedestruction of glands (1* Hyp)

PSEUDO HYPO.-inherited,biologically inactivePTH but w/ endorgan resistance toeffects

HYPERPARATHY.-excessive PTH dueto*parthyroid tumor *hyperplasia/ectopicproduction of PTHor PTH-relatedpeptide-found incarcinomas &hypercalcemia of malignancy

/acdg 7



2. Calcitonin *Parafollicular or C cells inthyroid gland*lung*GIT

*Extracell concof ionized Ca*elevated Calevels

*Bone – suppress resorptionof bone; inhibit osteoclasts

*Kidney – inhibitreabsorption of Ca & p inkidney tubules = +loss inurine

*Participates in Ca & Pmetabolism*32 aa peptide cleaved fromlarger prohormone*single disulfide bond = ring

HORMONE

Affect Na Levels

SOURCE STIMULI EFFECTS ON ORGANS SPECIAL TRAITS CLASSIFIC. PATHO -

PHYSIOLOGY1. Atrial NatriureticPeptide (ANP or Atriopeptin I)

*synthesized &stored as 126aa prehormonebyCARDIOCYTESin atrium,secreted asactive dimmer converted toactive monomer

*increasedblood volume &central venouspressure*high bloodpressure*+ serumosmolarity*+ heart rate*+ levels of catecholamines

* + GFR, sodium excretion(NATRIURESIS)* (-) secretion of ADH fromcells in post. pituitary

* 28 aa peptide w/ single cys-cys bridge

2. Angiotensin *stimulates aldosteroneproduction/secretion &vasoconstriction

*Octapeptide w/ multiplebiological actions*Binds to plasma membranereceptors of cells inGLOMERULOSA LAYER of Adrenal Cortex, vascular smooth muscle cells, & other target tissues

/acdg 8

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