Endo Kamis

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Endocrine System

dr. Rhiza Mohammad Ishaq Sobari

Physiology dept.



• Endocrine it derives from the Greek words endo

(Greek ένδο) meaning inside, within, and crinis

(Greek κρινής) for secrete.

• The endocrine system is an information signalsystem like the nervous system.

• Hormones are substances (chemical mediators)

released from endocrine tissue into the

bloodstream that attach to target tissue and allow

communication among cells.



• Hormones regulate many functions of an organism,

including – stimulation or inhibition of growth

– mood swings

– induction or suppression of apoptosis

– activation or inhibition of the immune system – regulation of metabolism

– preparation of the body for mating, fighting, fleeing, and

other activity

– preparation of the body for a new phase of life, such as

puberty, parenting, and menopause

– control of the reproductive cycle

– hunger cravings



Endocrine Glands:

Secretion and Action of Hormones

• Most, if not all, tissues secrete hormones.

• Hormone = chemical secreted into theblood that triggers a preprogrammed

response in the target cell.• Neurotransmitter = chemical secreted into

synaptic cleft that affects ion channels inthe target cell.

• Neurohormone = chemical secreted byneurons into the blood.



Classification of hormones

1. By composition:a. Amino-acids derivatives,ex: epinephrine (E), norepinephrine (NE),

dopamine (E, NE & dopamine are structurally similar → calledcatecholamines) the thyroid hormones, and melatonin.

b. Peptide

a. Polypeptide,ex: ADH, oxytocin, prolactin

b. Glycoprotein,ex: TSH, LH, FSH

c. Lipid derivatives:

a. Steroid hormone, ex: androgens, estrogens, progesterons,corticosteroids,calcitriol

b. Eicosanoids, ex : leucotrienes, prostaglandins (paracrinefactors)

2. By polarity:

a. Nonpolar (hydrophobic) – soluble in lipids – steroids and thyroidhormones.

b. Polar (hydrophilic) – soluble in water – all others.



Types of cell-to-cell signaling

• Classic endocrinehormones travel via

bloodstream to target

cells;

• neurohormones arereleased via synapses

and travel via the

bloostream;

• paracrine hormones acton adjacent cells and

• autocrine hormones are

released and act on the

cell that secreted them..



Regulation of hormone secretion

Sensing and signaling: a biological need is sensed,

the endocrine system sends out a signal to a target

cell whose action addresses the biological need. Key

features of this stimulus response system are: receipt of stimulus

synthesis and secretion of hormone

delivery of hormone to target cell

evoking target cell response

degradation of hormone



Control of Endocrine Activity

•The physiologic effects of hormones

depend largely on their concentration in

blood and extracellular fluid.

• Almost inevitably, disease results when

hormone concentrations are either too high or

too low, and precise control over circulatingconcentrations of hormones is therefore

crucial.




The concentration of hormone as seen by

target cells is determined by three factors:

•Rate of production

•Rate of delivery

•Rate of degradation and elimination




Rate of production: Synthesis and secretion of

hormones are the most highly regulated aspect

of endocrine control. Such control is mediated

by positive and negative feedback circuits, as

described below in more detail.




Rate of delivery: An example of this effect is

blood flow to a target organ or group of target

cells - high blood flow delivers more hormone

than low blood flow.




Rate of degradation and elimination:

Hormones, like all biomolecules, have

characteristic rates of decay, and are

metabolized and excreted from the bodythrough several routes.

Shutting off secretion of a hormone that has a

very short half-life causes circulating hormoneconcentration to plummet, but if a hormone's

biological half-life is long, effective

concentrations persist for some time after

secretion ceases.



Feedback Control of Hormone

Production

Feedback loops are used

extensively to regulate

secretion of hormones inthe hypothalamic-pituitary

axis. An important example

of a negative feedback loop

is seen in control of thyroidhormone secretion



Inputs to endocrine cells



Hormone receptor

• A hormone receptor is a receptor protein on thesurface of a cell or in its interior that binds to a

specific hormone. The hormone causes many

changes to take place in the cell.

• Binding of hormones to hormone receptors often

trigger the start of a biophysical signal that can

lead to further signal transduction pathways, or

trigger the activation or inhibition of genes.• Types of Hormone Receptors

– Steroid hormone receptors

– Peptide hormone receptors



• Hormon mengaktifasi reseptor protein,kompleks

protein-g dan α,β,ɣ yg inaktif akanteraktifasi,mnyebabkan disosiasi subunit α dari

subunit β,ɣ dan protein-g,dan interaksi ini

menginisiasi pnghantaran sinyal intrasel yg akan

mengubah fungsi sel : aktif/inaktif



Steroid Hormones

• Steroid hormones and thyroid hormone diffuse easilyinto their target cells

• Once inside, they bind and activate a specificintracellular receptor

• The hormone-receptor complex travels to thenucleus and binds a DNA-associated receptor protein

• This interaction prompts DNA transcription to

produce mRNA• The mRNA is translated into proteins, which bring

about a cellular effect



Figure 16..3

Steroid Hormones

• Hormon binding dgn reseptor sitoplasma/nukleus, kompleks

hormon-reseptor akan berikatan dengan hormon respon

element(promotor) pada DNA,menyebabkan

aktifasi/inaktifasi transkripsi gen+pembentukan

mRNA+sintesis protein



• ELISA : A sensitiveimmunoassay that uses anenzyme linked to an antibodyor antigen as a marker for the

detection of a specific protein,especially an antigen orantibody. It is often used as adiagnostic test to determineexposure to a particularinfectious agent, such as the

AIDS virus, by identifyingantibodies present in a bloodsample.

• RIA : A procedure that measuresminute amounts of a substance,such as a hormone or drug, byquantitating the binding, or the

inhibition of binding, of aradiolabeled substance to anantibody.



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Major Hormones

Where Hormone Is Produced Hormone Function

Pituitary gland Antidiuretic hormone (vasopressin) Causes kidneys to retain water and, along with aldosterone, helps control

blood pressure

Corticotropin (ACTH) Controls the production and secretion of hormones by the adrenal glands

Growth hormone Controls growth and development; promotes protein production

Luteinizing hormone and follicle-stimulating

hormone

Control reproductive functions, including the production of sperm and semen,

egg maturation, and menstrual cycles; control male and female sexual

characteristics (including hair distribution, muscle formation, skin texture and

thickness, voice, and perhaps even personality traits)

Oxytocin Causes muscles of the uterus and milk ducts in the breast to contract

Prolactin Starts and maintains milk production in the ductal glands of the breast

(mammary glands)

Thyroid-stimulating hormone Stimulates the production and secretion of hormones by the thyroid gland

Parathyroid glands Parathyroid hormone Controls bone formation and the excretion of calcium and phosphorus

Thyroid gland Thyroid hormone Regulates the rate at which the body functions (metabolic rate)

Calcitonin In people, function is unclear; in other species, regulates calcium balance

Adrenal glands Aldosterone Helps regulate salt and water balance by retaining salt and water and

excreting potassium

Cortisol Has widespread effects throughout the body; especially has anti-inflammatory

action; maintains blood sugar level, blood pressure, and muscle strength;

helps control salt and water balance

Dehydroepiandrosterone (DHEA) Has effects on bone, mood, and the immune system

Epinephrine and norepinephrine Stimulate the heart, lungs, blood vessels, and nervous system

Pancreas Glucagon Raises the blood sugar level

Insulin Lowers the blood sugar level; affects the processing (metabolism) of sugar,

protein, and fat throughout the body

Kidneys Erythropoietin Stimulates red blood cell production

Renin Controls blood pressure



Ovaries Estrogen Controls the development of female sex characteristics

and the reproductive system

Progesterone Prepares the lining of the uterus for implantation of a

fertilized egg and readies the mammary glands to secrete

milk

Testes Testosterone Controls the development of male sex characteristics and

the reproductive system

Digestive tract Cholecystokinin Controls gallbladder contractions that cause bile to enter

the intestine; stimulates release of digestive enzymes

from the pancreas

Glucagon-like peptide Increases insulin release from pancreas

Ghrelin Controls growth hormone release from the pituitary

gland; causes sensation of hunger

Adipose (fat) tissue Resistin Blocks the effects of insulin on muscle

Leptin Controls appetite

Placenta Chorionic gonadotropin Stimulates ovaries to continue to release progesterone

during early pregnancy

Estrogen and progesterone Keep uterus receptive to fetus and placenta during

pregnancy



The Endocrine System

• Consists of several

glands located in

various parts of the

body.

• Pituitary gland: a smallgland located on a stalk

hanging from the base of the

brain.

• “The Master Gland”

– Primary function is to

control other glands.

– Produces many

hormones.

– Secretion is controlled by

the hypothalamus in the

base of the brain.




• The Pituitary Gland isdivided into 2 areas,which differ

– structurally and

functionally – each area has

separate types ofhormone production.

• The two segments are: – Posterior Pituitary:

• produces oxytocinand antidiuretichormone (ADH)

– Anterior Pituitary:• produces thyroid-

stimulating hormone(TSH)

• growth hormone (GH)

• adrenocorticotropin(ACTH)

• follicle-stimulatinghormone (FSH)




– luteinizing hormone

(LH)

– prolactin

• Posterior Pituitary

– Oxytocin (the natural

form of pitocin)

• stimulates gravid

uterus

• causes “let down”

of milk from the

breast.

– ADH (vasopressin)

causes the kidney to

retain water.




• Anterior Pituitary – Primarily regulates

other endocrine glands

– rarely a factor in

endocrinological

emergencies

– TSH stimulates the

thyroid gland to

release its hormones,

thus metabolic rate

• Anterior Pituitary… – Growth hormone (GH)

• glucose usage

• consumption of

fats as an energysource

– ACTH stimulates the

adrenal cortex to

release its hormones

– FSH & LH stimulatesmaturation & release

of eggs from ovary.




• The Thyroid Gland – lies in the anterior

neck just below thelarynyx.

– Two lobes, locatedon either side of thetrachea, connectedby a narrow band oftissue called thei s thmus

. – Sacs inside the

gland contain col lo id

• Within the colloid arethe thyroid hormones:

– thyroxine (T4)

– triiodothyronine (T3)

• When stimulated(by TSH or bycold), these arereleased into thecirculatory systemand themetabolic rate.




• “C” cells within the thyroid produce thehormone calc i tonin

• Calcitonin, when released, lowers the

amount of calcium in the blood.




• Parathyroid Glands

– small, pea-shaped

glands, located in the

neck near the thyroid

– usually 4 - number can

vary

– regulate the level of

calcium in the body

– produce parathyroid

hormone - level of

calcium in blood

– Hypocalcemia can result

if parathyroids are

removed or destroyed.




• Pancreas

– a key gland located inthe folds of theduodenum

– has both endocrine andexocrine functions

– secretes several keydigestive enzymes

• Islets of Langerhans

– specialized tissues inwhich the endocrinefunctions of thepancreas occurs

– include 3 types of cells:

• alpha ( )

• beta ( )

• delta () – each secretes an

important hormone.




• Alpha ( ) cells releaseglucagon, essential forcontrolling bloodglucose levels.

• When blood glucoselevels fall, cells theamount of glucagon inthe blood .

• The surge of glucagonstimulates the liver torelease glucose stores(from glycogen and

additional storagesites).

• Also, glucagonstimulates the liver to

manufacture glucose -

• gluconeogenesis.




• Beta Cells ( ) release

insulin (antagonistic to

glucagon).

• Insulin the rate atwhich various body cells

take up glucose. Thus,

insulin lowers the blood

glucose level.

• Insulin is rapidly broken

down by the liver and

must be secreted

constantly.• Delta Cells () produce

somatostatin, which

inhibits both glucagon

and insulin.




• Adrenal Glands – 2 small glands that sit

atop both kidneys.

– Each has 2 divisions,

each with differentfunctions.

– the Adrenal Medulla

secretes the

catecholaminehormones

• norepinephrine and

epinephrine (closely

related to the sympatheticcomponent of the

autonomic nervous

system).



The adrenal cortex is composed of 3 zones:1. Zona Glomerulosa – superficial layer

– secretes mineralocorticoids(aldosterone)

2. Zona Fasciculata – middle layer – secretes glucocorticoids (cortisol)

3. Zona Reticularis – deep layer – secretes gluco-corticoids and sex

steroids.Fetal Zone – only in fetus – makes

DHEA for conversion to sex steroids(mostly estrogens) by the placenta.

T



Gonads • Testes – secreteandrogens; principallytestosterone from Leydigcells of seminiferous

tubules. Androgenscontrol development andmaintenance of sex organsand secondary sexcharacteristics.

• Ovaries – secreteprogesterone andestrogens; principallyestradiol-17. – Estradiol is secreted from

granulosa cells of theovarian follicle.

– Progesterone and estradiolis secreted from the corpusluteum.



Hipothalamus & Hipofisis

dr. Rhiza Mohammad Ishaq Sobari

Physiology dept.



Hipothalamus

• Tidak memiliki batas tegas• Bagian atas dibatasi dari daerah thalamus dgn sulcus

hipothalamicus

• Hasilkan hormon

Growth hormon releasing hormon (GHRH)Somatostatin (inhibisi GH & TSH)

Dopamin

Prolactin Releasing Factor

Thyrotropin releasing hormon (TRH)Corticotropin releasing hormon (CRH)

Gonadotropin releasing hormon (GnRH)



Hipofisis

• Kel hipofisis terletak didasar tengkorak (sella

tursica/fossa pituitaria)

• Terdiri dari :

- hipofisis anterior (adenohipofisis)

- pars intermedius (jadi satu dgn dorsal

hipofisis posterior)- hipofisis posterior (neurohipofisis)



Fisiologi Adenohipofisis

• Mengeluarkan hormon :1. Hormon pertumbuhan

2. Prolaktin

3. Tiroid Stimulating Hormon (TSH)

4. Adrenocorticotropic hormon (ACTH)

5. Hormon gonadotropin :

- Follicle Stimulating Hormon (FSH)

- Luteinizing Hormon (LH)6. Melanocyte stimulating hormon (MSH)



Fisiologi pars intermedius

• Mengeluarkan hormon MSH

• Terdiri 2 sub unit alfa & beta

• Beta MSH ~ ACTH

• Pd manusia dewasa rudimenter



Fisiologi Neurohipofisis

• Menghasilkan hormon :

- Oksitosin

- Anti Diuretik Hormon (ADH/ Arginin

vasopresin)

• Dikendalikan nuklei hipothalamus

• Sekresi oksitosin dikendalikan nukleus

paraventrikularis• Sekresi ADH dikendalikan niklei supraoptici



Stimuli nukleus paraventrikularis (oksitosin)

- uterus, cervix,vagina

- papilla & areola mammae

Penting proses melahirkan, kontraksimiometrium, menyusui

Nuleus supraoptici (ADH)

Osmoreseptor peka thd perubahan kepekatanplasma



Fisiologi adenoh



Endocrine regulation in growth




A system of glands that secrete hormones

Regulate a variety of physiological processes

Endocrine hormone:

Travels through bloodstream to target organ,where it exerts its effects by binding to itsreceptor.

Receptor: Membrane (Protein Hormone)

Nuclear (Steroid Hormone)



Thyroid Hormones

Hypothalamus TRH (Thyrotropin releasing hormone)

Pituitary

TSH (Thyroid stimulating hormone)

Thyroid

T4 thyroxine T3 thyronine

iodine

Permissive role:

Allow for normal cell function & growthInduce N retention for protein synthesis

Stimulate growth H release

Increases metabolic rate



Roles

• Metabolic Rate• BMR

• ↑ heat production• Newborns

• Stress

• Weight regulation

• SNS Activity• ↑ -receptors

• ↑ Heart rate

• Brain activity, muscle activity

• Brain development and body growth

• Stimulates GH release

Th id h ( )



•Thyroid hormones (cont.)

• Secreted by fetus from week 20 on• Necessary for fetal protein synthesis and brain

development

• Thyroid hormone deficiency• In Utero:

• Cretinism (Congenital hypothyroidism mentalretardation, stunting)

• In infancy:

• growth delay, may CNS damage

•

In childhood / adolescence:• growth delay, skeletal maturity delay, does not

CNS damage

• In adulthood:

• T3T4 deficiency obesity

•

T3T4 excess weight loss



Hypothyroidism

http://www.bupa.co.uk/wellness/images/factsheets/Thyroid_disease1.gif

Goitre: iodine

deficiency

No goitre: TSH

deficiency



Hyperthyroidism

http://www.bupa.co.uk/wellness/images/factsheets/Thyroid_disease2.gif



Growth Hormone

Hypothalamus

Anterior pituitary gland

+ GHRH Somatostatin -

GH

Liver

Cartilage and bonegrowthMuscle and otherorgans:-Protein synthesisand growth

Adipose Tissue-lipolysis- release of FFAs

Most Tissuesglucose utilization- blood glucose

IGF-1

Somatomedin

GH levels and effects are

most pronounced during

puberty



•Growth hormone disorders

• Excess GH

• Pre-puberty: gigantism bone growth, > 7 ft. tall

• Post-puberty: acromegaly Some tissues still grow: cartilage in

nose, hands, feet, ridges of eyebrow,chin, tongue

Metabolic effects: constant increase in

blood sugar, increased insulin type 2diabetes. Can also increase musclenarrowing of arteries, heart attack



• GH Deficiency

• ↓ GH, ↓ IGF-1

• Short stature

• Metabolic effects



Insulin

• Hormone of Feasting• From Pancreas - cells from Islets of Langerhans• Allows glucose to enter the cell

• glucose uptake into tissues• Affects glucose transporter

• Energy• Metabolic Processes

• ↑ Glycogen synthesis• ↑ Fat synthesis• ↑ Protein synthesis

•

Growth

• Children with poorly controlled Type I diabetes often haveshort stature

• Glucagon – Hormone of Fasting



•Insulin Deficiency

• ↑ Lipolysis

• FFA ketone bodies acidifies blood

• ↑ Protein breakdown

• ↑ Plasma Glucose

• Osmotic diuresis

• ↑ water excretion

•

plasma volume• arterial blood pressure

• brain blood flow



Androgens and Estrogens

• Produced in gonads (ovaries, testes) and adrenalglands, in puberty

• Will fuse epiphysis and stop linear growth• - earlier puberty in women contributes to their

shorter stature

• Androgens• Primarily DHEA (dihydroepiandrosterone)• Converted to estrogens, testosterone in

tissues• Peaks in young adults• Secondary sex characteristics• In women: DHEA stimulates growth in

adolescence, e.g. muscle, bone• Important during fetal period and during

menopause



Estrogen

During puberty: 2º sex characteristics

Promotes growth of uterus

Stabilizes blood cells in skin Bone strength



Gangguan fungsi hipofisis

Panhipopituitarisme

• kekurangan hormon :

– GH, TSH, ACTH, Gonadotropin,Prolaktin

• Gejala sesuai kekurangan hormon

• Etiologi :infeksi,iskemia,neoplasma,

granuloma,aneurisma dll



• Akromegali / gigantisme

Hipersekresi GH / HP

Sesudah epifises menutup : akromegali

Sebelum epifises menutup : gigantismeAkibat tumor hipofisis

Gejala :

Bentuk muka berubah, pertumbuhan gigi tak teratur,

kiposis, atropati, pertumbuhan tulang ekstremitasberlebihan



• Pembesaran dan penebalan hidung, lidah, bibir,telinga, tangan dan kaki

• Kulit menebal, basah dan beminyak, lipatan kulitkasar dan melebar, penebalan telapak kaki

• Suara parau

• Pada metabolisme : intoleransi glukosa,hiperfosfatemia, hiperlipidemia dan hiperkalsemia,osteoporosis.



• Gambaran klinis akibat tumor- Pembesaran keatas :

sakit kepala, ggn penglihatan

- Pembesaran ke lateral :

kelumpuhan syaraf III,IV,V dan VI- Penyumbatan pemb darah lokal

- Pertumbuhan ke inferior :

CSF rinorea

- Pertumbuhan ke anterior :

perubahan kepribadian- Infark



b h



Gangguan Pertumbuhan

• Defisiensi hormon pertumbuhan

• Manifestasi perawakan pendek (shurt stature)

• Etiologi perawakan pendek

• Defek intrinsik : displasia tulang,kelainan kromosom,kecebolan primordial

• Lingkungan : ggn gizi,gagal ginjal kronik, penyakit

darah dll

• Hormonal : defisiensi HP, defisiensi tiroid, kelebihan

glukokortikoid



G b h



Gangguan pertumbuhan

• Gambaran klinis HP <<

perawakan pendek berat (cebol), agak gemuk,

lemak subcutan di abdomen bertambah,

hipoglikemia, proporsi tulangnormal,pematangan tulang terlambat.

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