BAI GIANG VE HE NOI TIET (Endocrine System)

Signal transduction pathways triggered by hormones Hormone-−Hormone-receptor interaction − Membrane-bound receptors for lipophobic hormones − signal transduction pathways with the 2 nd m

Endocrine system

After studying this chapter, students are able to know:

−the difference between endocrine and neural control

− different types of intercellular chemical signals and signallings

− to differentiate between endocrine and exocrine glands

− Hormones, chemical classes of hormones define their properties: target cell interactions Signal transduction pathways triggered by hormones

Hormone-−Hormone-receptor interaction

− Membrane-bound receptors for lipophobic hormones

− signal transduction pathways with the 2 nd messenger system: cAMP,c GMP, IP3, DAG, Ca2+

− intracellular receptors for lipophilic hormones and the regulation of gene expression and protein synthesis

−The main endocrine glands/ tissues /structures in human

− The hypothalamus-pituitary-target gland axis and negative feedback control of endocrine glands

−Hypothalamus and neurohormones

− Pituitary gland and its hormones

−Thyroid gland and thyroid hormones The synthesis of thyroid hormones, the role

of iodine in the synthesis of thyroid hormones Hyper-and hypothyroidism

− Parathyroid gland and the role of its hormones in regulating blood calcium

concentration

−Adrenal gland, corticosteroid hormones and catecholamines

− Pancreas gland Insulin, glucagon and diabetes mellitus

− Sex hormones and functions

Specific terms and keywords

Endocrine system and nervous system - the two

main control systems in the body

• The endocrine system, together with the nervous system, work to

control and coordinate the cells to accomplish physiological activities

and function of animals

• The endocrine system works differently from how the nervous

system does:

- electrical signal and chemical signals - chemical signals (hormones)

- precisely targeted (neural signals

are precisely targeted)

- broadcast (endocrine signals are broadly distributed throughout the animal’s body)

- controls predominantly the fine, rapid

movements of discrete muscles

- controls more widespread, prolong activities (e.g.metabolic changes)

• The nervous system and the endocrine system can control one another

Rõ ràng, chính xác

Phần lớn, chủ yếu là

Endocrine signal is one type of intercellular chemical

Endocrine and Exocrine glands

http://www.fotosearch.com/comp/LIF/LIF115/SA401031.jpg

Hormone and its properties

• Hormone is a chemical substance produced and released by

• Hormones are chemical messengers transporting signal

from one cell to another -> they convey information from

hormonal signal is amplified by hormonal cascade effects

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Hormone interactions

• One hormone can target different cell types -> can produce more

than one effect in the body (eg ADH affects epithelial cells in the kidneys (increasing water reabsorption) and smooth muscle cells of some blood vessels (causing vasoconstriction of these vessels)

• One body function is regulated by more than one hormone (eg

Blood Ca2+ is controlled by calcitonin, PTH, vitamin D3; blood

glucose by insulin, glucagon, epinerphrine, cortisol, GH)

process

effect can be addictive (net effect equals the sum of individual

effects) or synergistic (net effect is greater than the sum of

individual effects)

• If the presence of one hormone is needed for another hormone

to be effective: permissiveness process (e.g thyroid hormone stimulates beta adrenergic receptor expression needed for

epinephrine to be effective on smooth muscle cells of bronchioles (dilating bronchioles)

Sự co mạch

chống chọi, phản đối

Chemical classification of hormones

Properties of hormones

depend mainly

on whether they are lipophilic or

lipophobic

Amino acids Glutamate, aspartate, glycine, gamma-aminobutyric

acid (GABA)

hydrophilic, lipophobic

Amines Catecholamines: dopamine, norepinephrine,

epinephrine (tyrosine derivatives)

Thyroid hormones (tyrosine derivatives) Serotonine (tryptophan derivatives) Histamine (histidine derivatives)

Hydrophilic, lipophobic

Glycoprotein FSH, LH,TSH,PTH

Steroids Estrogen

Progestin (progesterone) Testosterone

Mineralocorticoid Glucocorticoid

Hydrophobic, lipophilic

Fatty acid Derivativatives of arachidonic acid: prostaglandins,

leukotriens, thromboxanes

Hydrophobic, lipophilic

The synthesis of peptide/protein hormones

Fig 5.4 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

The release and transport of hormone in blood

• H-Pr <-> H + Pr

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Hormone – target cell interaction

Properties of receptors

• Specificity: a receptor binds only one hormone/

messenger or a class of messengers

• The binding between a hormone and a receptor is a

brief, reversible chemical

interaction

• Affinity: the strength of the binding between a

messenger and its receptor

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Hormone signal transduction pathway

1 signal reception

2 signal transduction

3 response of the target cell

fig.cox.miami.edu/~cmallery/150/memb/cellcomm.htm

Receptor agonist and receptor antagonist

• Agonists: ligands that bind to receptors and

produce a biological response

• Antagonists: ligands that bind to receptors

but do not produce a biological response

• Antagonists may compete with agonists for the receptor, blocking or decreasing the

effects of agonists on target cells

application in drug design and drug

target

Location of receptors in target cells

• Location of receptors in target cells depends on

whether the messenger/hormone is lipophilic or lipophobic

• membrane bound receptor

– Lipophobic/hydrophilic hormones

– large hormone molecules

– Modes of action:

1 regulate channel-linked receptor

2 activate intracellular enzymes by phosphorylation

3 activate G protein

• intracellular receptor

– receptors in cytosol or in the nucleus of target cells

– Lipophilic (lipid-solube) hormones

Fast ligand-gated calcium channels

Fig 5.13 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

enzyme-linked receptor

• The receptor and the enzyme (mainly tyrosine kinase) are the same protein

• H-R changes enzyme conformation-> activate tyrosine kinase ->

phosphorylation of intracellular proteins-> cellular responses

– Insulin – GH – Prolactin

– Growth factors

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Channel - linked receptor

•fast channel: receptor and

channel are the same protein

−Acetylcholin : Na+ (excitatory)

−Serotonin: Na+ (excitatory)

−Glutamat: Na+ (excitatory)

−Glycine: Cl- (inhibitory)

−GABA: Cl- (inhibitory)

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

:G-• When activated: α –GTP

moves to the effectors

changing effectors activity

• Effectors: ion channels

(slow ligand gated ion channels) or enzymes

• 3 main types of G proteins:

– G-Proteins affecting ion channels

– stimulatory G protein (Gs protein)

– inhibitory G protein (Gi protein)

Slow ligand-gated ion channel

Fig.5.15 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Gs and Gi proteins activate and inhibit, respectively, enzymes

(amplifier enzymes) catalyzing the production of 2nd messengers

H- G-protein R -> Adenylate cyclase- > cAMP ->

protein kinase A

cAMP: epinephrine glucose

fig.cox.miami.edu/~cmallery/150/memb/cellcomm.htm

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

• H- G protein R-> guanylate cyclase->

cGMP -> protein kinase G

H- G-protein R -> phospholipase C- > PIP2 ->

DAG -> protein kinase C

IP3 -> Ca 2+

5.17 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Second messenger systems

Table 5.3.C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Bệnh dịch tả

Lipophilic hormones cross the plasma cell membrane, binding to intracellular receptors, modulating gene expression and protein synthesis of target cells

Fig 5.11 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Human endocrine glands/organs

Vùng dưới đồi

Tuyến yên

Tinh hoàn Buồng trứng

Da

Fig 6.1 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

The 4-level control of endocrine system

CNS Hypothalamus

Pituitary Target glands

-C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

The hypothalamus produces releasing and inhibiting hormones

regulating pituitary hormone production and secretion

• Hormones produced in the hypothalamus are

neurohormones

• Hypothalamus hormones are

tropic/trophic hormones as they regulate the secretion of other hormones:

– Releasing hormones stimulate hormone production and secretion of pituitary gland

• PRH (prolactin releasing hormone): stimulates prolactin secretion

• TRH (thyrotropin releasing hormone): TSH

• GnRH (gonadotropin releasing hormone): FSH, LH

• GHRH (growth hormone releasing hormone): GH

• CRH (corticotropin releasing hormone): ACTH

– Inhibiting hormones inhibit the secretion of some hormones from pituitary gland

• Somatostatin (GHIH): inhibits GH, TSH secretion

• Dopamin (PIH): inhibits prolactin (PRL) secretion

• Oxytocin

• Vasopressin (ADH)

Fig 6.4 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

The pituitary gland

• anterior pituitary – adenohypophysis: produce and

secrets hormones

•posterior pituitary neurohypophysis: store hormones

produced in the hypothalamus

Hormones of pituitary gland

• Hormones produced and released

by the anterior pituitary: trophic hormones

– TSH (thyroid-stimulating hormone/ thyrotropin)

– ACTH (Adrenocorticotropichormone/corticotropin)

– GH (growth hormone)– LH (luteinizing hormone/ lutropin)

– FSH (Follicle-stimulating hormone)

– Prolactin

• Hormones released by the posterior pituitary:

– ADH, vasopressin – Oxytocin

Fig 6.4 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Fig 20.2 Caroline Bunker Rosdahl, Mary T Kowalsk Textbook of basic nursing 9e 2008

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Structure of growth hormone

• 191 a.a

• 21.500 (human)

• 42.250 (pig)

http://www.endotext.org/neuroendo/neuroendo5e/figures/figure1.jpg

• Factors affecting GH secretion:

– GHRH (growth hormone releasing hormone) – GHIH (growth hormone inhibiting hormone/ somatostatin)

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

mỡ

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Deficiency and excess of growth hormone

http://www.commonwealthadoption.org/images/johnston.jpg

•Growth hormone deficiency:

pituitary dwarfism :

•short stature

• slow rate of growth

• normal body proportions

• normal intelligence

•late puberty -> recombinant GH

• Excess of GH

ACTH (adrenocorticotrophic hormone)

• 39a.a

• POMC (367a.a)

derivative

• Stimulates hormone production of adrenal cortex

• G-protein receptor- cAMP-protein kinase A

ACTH

-MSH

http://web.indstate.edu/thcme/mwking/pomc.gif

LH, FSH and prolactin

• LH (luteinizing hormone): stimulates ovulation, and

development of the corpus luteum in female, sex

hormone secretion in the gonads (estrogens,

progesterone in females; androgens in males)

• FSH (follicle stimulating hormone): promotes the

development of egg cells (female), sperm cells (male), stimulates estrogen secretion in female

• LH and FSH act synergistically in reproduction

• Prolactin stimulates mammary gland development and milk secretion in females

Kích thích tuyến sữa

vú

Hormones from posterior pituitary

• ADH

– ADH: increases water reabsorption in renal tubules, simulates vasoconstriction, increases blood pressure – G-protein receptor- cAMP

• Oxytocin

– stimulates the contraction of smooth muscle of the uterus – stimulates milk ejection during lactation in mammals

http://dl.clackamas.edu/ch106-08/images/68065.jpg

Synthesis and secretion of thyroid hormones

In the colloid:

- Thyroglobulin (TG) in coloid- precusor for thyroid H.

- Enzymes for thyroid hormone synthesis

4 TSH – receptor binding> cAMP > Protein kinase

-> activate enzymes needed for T3, T4 releasing

5 Follicular cells take TG-T3-T4 by phagocytosis

6 Phagosome containing TG-T3-T4 fuses with lysosome

7 Lysosomal enzymes break down TG-T3-T4 -> free T3, T4 diffuse into the blood stream

The role of Iodine in thyroid

hormone synthesis

Fi g 21.16 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Actions of thryroid hormones

• Are lipophilic hormones -> bind to receptor in the nuclei affecting gene

expression and protein synthesis

• Raise the body’s basal metabolic rate, energy utilization

• At higher-than-normal doses: increase energy mobilization by promoting

glycogenolysis, conversion of muscle protein to amino acids,

gluconeogenesis and lipolysis

• At lower-than-normal doses: promote glycogenesis and protein synthesis

• Permissive effects: e.g promote synthesis of of beta andrenergic receptors (for epinephrine and norepinephrine), permitting tissues response to

sympathetic neural input and to epinephrine

• Are needed for normal growth and development and function of many

tissues (by stimulation of GH release (in synergism with glucocorticoids), and by permissiveness to GH in target tissue)

• Are especially important for the development of nervous system:

– Cretinism: thyroid hormone deficiency in infants caused retarded mental development and stunted growth

Regulation of thyroid hormone secretion

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Thyroid disorders

• Hyperthyrodism

– Basedow (Grave’s disease)

• Hypothyrodism

– Iodine deficiency Goiter

http://healthlineinfo.com/goiter-symptoms-diagnosis-and-treatment.html

http://www.thachers.org/images/Graves.jpg

• Produced by C cells

• Target organ: bone

• Binds to membrane bound receptors -> decreases

osteoclast activity, increases osteblast activity ->

Ca, P plasma concentration

Tế bào C

• G-protein receptor-cAMP

• stimulates osteoclast activity, increases Ca2+ reabsorption in renal

tubules and in intestine

• Increases renal P secretion

http://www.univ-st-etienne.fr/lbti/Mednucl/AtlasEnd/parathy/abase5.htm

84 a.a, 95.000

The adrenal glands

• adrenal cortex

• adrenal medulla: modification of a sympathetic ganglion

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Hormones of adrenal cortex

• Steroid hormones, cholesterol derivatives

• Bind to intracellular receptors, regulating gene

expression and protein synthesis of target cells

– At high doses: inhibits inflammation and allergic reactions – is increased in stress response: stress hormone

– Is required for GH secretion and for normal responsiveness

of blood vessels to vasoconstrictive stimuli (sympathetic, epinerphrine, angiotensin II)

– Androgen

• Testosterone