Endocrine system

Copyright © 2010 Pearson Education, Inc.

Endocrine system


Hormone

The term hormone is derived from a Greek verb meaning

– to excite or arouse Hormone is a chemical messenger that is released in one

tissue (endocrine tissue/gland) and transported in the

bloodstream to reach specific cells in other tissues Regulate the metabolic function of other cells

Have lag times ranging from seconds to hours

Tend to have prolonged effects

Hormone actions must be terminated – how?


Endocrine versus Nervous system

• Released in synapse

• Close to target cells

• Signal to release by action potential

• Short live effect

• Crisis management

• Released to bloodstream

• Can be distant from target cells

• Different types of signal

• Long term effect

• Ongoing processes

Neurotransmitters Hormones

• Both use chemical communication

• Both are being regulated primarily by negative feedback


Intercellular communication types

• Autocrine - the cell signals itself through a chemical that it synthesizes and then responds to. Autocrine signaling can occur:

• solely within the cytoplasm of the cell or

• by a secreted chemical interacting with receptors on the surface of the same cell

• Paracrine - chemical signals that diffuse into the area and interact with receptors on nearby cells (cells within the same tissue).

• Endocrine - the chemicals are secreted into the blood and carried by blood and tissue fluids to the cells they act upon.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/Hormones.html



Control of Hormone Release

Blood levels of hormones: Are controlled by negative feedback systems

Vary only within a narrow desirable range

Hormones are synthesized and released in response to: Humoral stimuli

Neural stimuli

Hormonal stimuli


Humoral Stimuli

Secretion of hormones in direct response to changing blood levels of ions and nutrients

Example: concentration of calcium ions in the blood

Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)

PTH causes Ca2+ concentrations to rise and the stimulus is removed


Neural Stimuli

• Neural stimuli – nerve fibers stimulate hormone release

• Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines

Figure 16.5b


Hormonal Stimuli

Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs

The hypothalamic hormones stimulate the anterior pituitary

In turn, pituitary hormones stimulate targets to secrete still more hormones


Classes of Hormones – by chemical structure

• Hormones can be divided into three groups

1. Amino acid derivatives

2. Peptide hormones

3. Lipid derivatives


Amino Acid Derivatives

• Derivatives of Tyrosine:

• Thyroid hormones

• Catecholamines

• Epinephrine, norepinephrine

• Derivatives of Tryptophan:

• Dopamine, serotonin, melatonin


Peptide Hormones

• 3 groups – glycoproteins, short peptides and small proteins

• Glycoproteins

• Proteins are more than 200 amino acids long and have carbohydrate side chains

• Thyroid-stimulating hormone (TSH)

• Luteinizing hormone (LH)

• Follicle-stimulating hormone (FSH)


Peptide Hormones

Short chain polypeptides

Antidiuretic hormone (ADH) and oxytocin (OXT) (each 9 amino acids long)

Small proteins

Growth hormone (GH; 191 amino acids) and prolactin (PRL; 198 amino acids) from the pituitary gland

Includes all hormones secreted by:

Hypothalamus, heart, thymus, digestive tract, pancreas, and posterior lobe of the pituitary gland, as well as several hormones produced in other organs


Lipid Derivatives – include Eicosanoids and steroids• Eicosanoids - derived from arachidonic acid, a 20-carbon

fatty acid

• Paracrine factors

• prostaglandins - involved primarily in coordinating local cellular activities

• Steroid hormones - derived from cholesterol

• Released by:

• The reproductive organs (androgens by the testes in males, estrogens and progestins by the ovaries in females)

• The cortex of the adrenal glands (corticosteroids)

• The kidneys (calcitriol)


A Structural Classification of Hormones


Distribution of Hormones in bloodstream

• Hormones that are released into the blood are being transported in one of 2 ways:

• Freely circulating

• Bound to transport protein


Distribution of Hormones in bloodstream

• Freely circulating (most hormones)

• Hormones that are freely circulating remain functional for less than one hour and some as little as 2 minutes

• Freely circulating hormones are inactivated when:

* bind to receptors on target cells

* being broken down by cells of the liver or kidneys

* being broken down by enzymes in the plasma or interstitial fluid

• Bound to transport proteins – thyroid and steroid hormones (>1% circulate freely)

• Remain in circulation longer

Copyright © 2010 Pearson Education, Inc. Table 7-1

Hormones: Classification


Target Cell Specificity

Hormones circulate to all tissues but only activate cells referred to as target cells

Target cells must have specific receptors to which the hormone binds

These receptors may be intracellular or located on the plasma membrane


Interaction of Hormones at Target Cells

• Three types of hormone interaction

• Permissiveness – one hormone cannot exert its effects without another hormone being present

• For example, thyroid hormone increases the number of receptors available for epinephrine at the latter's target cell, thereby increasing epinephrine's effect at that cell. Without the thyroid hormone, epinephrine would only have a weak effect

• Synergism – more than one hormone produces the same effects on a target cell

• Antagonism – one or more hormones opposes the action of another hormone


Target Cell Activation

Hormone exert their effects on target cells at very low blood concentrations (ng-10-9 gr; pg-10-12 gr)

Target cell activation depends on three factors

Blood levels of the hormone

Relative number of receptors on the target cell

The affinity of those receptors for the hormone

The time required to effect target cells depends on the hormone - some influence immediately and some (steroids; why?) require hours or days

Hormone effect duration also varies and can range between seconds to hours


• down regulation – the presence of the hormone induces a decrease in the receptors concentration;

• high levels of hormone – cell less sensitive

• Up regulation – absence of the hormone induces the increase in receptors concentration;

• Low levels of hormone – cell more sensitive

• In most systems the maximum biological response is achieved at concentrations of hormone lower than required to occupy all of the receptors on the cell (spare receptors).

• Examples:

• insulin stimulates maximum glucose oxidation in adipocytes with only 2-3% of receptors bound

• LH stimulates maximum testosterone production in Leydig cells when only 1% of receptors are bound

Receptors number on target cell


• In the cell membranes of target cells

• In the cytoplasm or nucleus

Receptors for hormones are located:


Mechanisms of Hormone Action

• Two mechanisms, depending on their chemical nature

1. Water-soluble hormones (all amino acid–based hormones

except thyroid hormone)

• Cannot enter the target cells

• Act on plasma membrane receptors

• Coupled by G proteins to intracellular second

messengers that mediate the target cell’s response

2. Lipid-soluble hormones (steroid and thyroid hormones)

• Act on intracellular receptors that directly activate genes


Receptors on the cell membrane

• Hormones do not induces changes in cell activity directly but via the induction of the appearance and action of other agents

• Hormones are referred to as first messengers and the agents that are activated by the hormones are called second messengers.

• All amino-acid hormones (with exception of the thyroid hormone) exert their signals through a second messenger system:

• cAMP

• PIP


Figure 16.2 1

The actions of second messengers for hormones that bind toreceptors in the plasma membrane

Effects on cAMP Levels Effects on Ca2+ LevelsMany G proteins, once activated, exert their effects by changing theconcentration of cyclic-AMP, which acts as the second messenger withinthe cell.

Some G proteins use Ca2+ as a secondmessenger.

Hormone Hormone Hormone

Proteinreceptor

Proteinreceptor

Proteinreceptor

G proteinactivated

G proteinactivated

G proteinactivated

Acts assecond

messenger

Increasedproduction

of cAMP

cAMP cAMP AMPATP

Opens ionchannels

Activatesenzymes

If levels of cAMP increase,enzymes may be activatedor ion channels may beopened, accelerating themetabolic activity of thecell.

In some instances, G proteinactivation results in decreasedlevels of cAMP in thecytoplasm. This decrease hasan inhibitory effect on the cell.

The calcium ions themselves serve asmessengers, generally in combinationwith an intracellular protein calledcalmodulin.

Enhancedbreakdown

of cAMP

Reducedenzymeactivity

Activatesenzymes

Ca2+

Ca2+Ca2+

Ca2+

Openingof Ca2+

channelsRelease ofstored Ca2+

from ERor SER

Ca2+ acts assecond messenger

Calmodulin

Hormone

Proteinreceptor

G protein(inactive)

G proteinactivated

Links the firstmessenger

(hormone) and thesecond messenger


Receptors on the cell membrane

• Second messengers function as enzyme activator, inhibitor or cofactor

• A small number of hormone molecules induce the appearance and activity of many 2nd messenger molecules – amplification

• one single hormone can induce the activation of more than one 2nd messenger

• Activation of a 2nd messenger can start a chain of reactions – receptor cascade


Amino Acid-Based Hormone Action: cAMP Second Messenger

• Hormone (first messenger) binds to its receptor, which then binds to a G protein

• The G protein is then activated

• Activated G protein activates the effector enzyme adenylate cyclase

• Adenylate cyclase generates cAMP (second messenger) from ATP

• cAMP activates protein kinases, which then cause cellular effects

Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 5

Hormone (1st messenger)binds receptor.

Receptoractivates Gprotein (GS).

G proteinactivatesadenylatecyclase.

cAMP acti-vates proteinkinases.

Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).

Receptor

G protein (GS)

Adenylate cyclase

Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)

Hormones thatact via cAMPmechanisms:

EpinephrineACTHFSHLH

Inactiveprotein kinase

Extracellular fluid

Cytoplasm

Activeproteinkinase

GDP

GlucagonPTHTSHCalcitonin

1

2 3 4

5


• Hormone binds to the receptor and activates G protein

• G protein binds and activates phospholipase

• Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers)

• DAG activates protein kinases; IP3 triggers release of Ca2+ stores

• Ca2+ (third messenger) alters cellular responses

Amino Acid-Based Hormone Action: PIP-Calcium


GTP PIP2

IP3

ReceptorGTP

GTP

CatecholaminesTRHADHGnRHOxytocin

Triggers responses of target cell

GDP

Extracellular fluid

Cytoplasm

Inactiveprotein kinase C

Activeprotein kinase C

Phospholipase C

Gq

Ca2+ Ca2+- calmodulin

Hormone

Endoplasmicreticulum

DAG1

2 34 5

5

6

Figure 16.3

Amino Acid-Based Hormone Action: PIP Mechanism


Steroid Hormones: Action

Figure 7-7, steps 1–5

1

Cellmembrane

Interstitialfluid

Cytoplasmicreceptor

Endoplasmicreticulum

Nucleus

Nuclear receptor

DNA

Translation

Cell surface receptor

Rapid responses

Transcriptionproduces mRNA

Steroid hormone

Bloodvessel

Proteincarrier

Newproteins

Steroid hormone receptors are in thecytoplasm or nucleus.

Most hydrophobic steroids are bound toplasma protein carriers. Only unboundhormones can diffuse into the target cell.

Translation produces new proteinsfor cell processes.

Some steroid hormones also bind to membrane receptors that use secondmessenger systems to create rapidcellular responses.

The receptor-hormone complex binds toDNA and activates or represses one ormore genes.

Activated genes create new mRNA thatmoves back to the cytoplasm.

2a

2

54

3

1

2a

2

3

4

5


Location of Receptor

Classes of Hormones

Principle Mechanism of Action

Cell surface receptors (plasma membrane)

Proteins and peptides, catecholamines and eicosanoids

Generation of second messengers which alter the activity of other molecules - usually enzymes - within the cell

Intracellular receptors (cytoplasm and/or nucleus)

Steroids and thyroid hormones

Alter transcriptional activity of responsive genes

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/change.html


How will we approach the endocrine system?

We will group them according to their function in the body:

Hormones that control blood glucose levels

Hormones that control minerals and water balance

Hormones that are involved in growth and metabolism

Hormones and the reproductive system


Pancreas structure

Exocrine pancreas (99% of volume)

Cells (pancreatic acini) forming glands and

ducts that secrete pancreatic fluid and enzymes

with digestive function

Endocrine pancreas (1%)

Small groups of cells scattered in clusters

(pancreatic islets) that secrete hormones


Pancreas – islets of Langerhans cells• The islets contain two major cell types:

• Alpha () cells that produce glucagon

• Beta () cells that produce insulin

• The islets also contain

• Delta cells – produce a peptide hormone identical to GH

inhibiting hormone (GH-IH). That hormone suppresses the

release of glucagon and insulin and slows food absorption and

digestive enzyme secretion

• F cells – Produce the hormone pancreatic polypeptide (pp) that

inhibits gallbladder contractions and regulate the production of

some pancreatic enzymes


Pancreas


How does the body control blood glucose levels• Blood Glucose Levels are controlled mainly by insulin

and glucagon

• When levels rise

• Beta cells secrete insulin, stimulating transport of glucose across plasma membranes

• When levels decline

• Alpha cells release glucagon, stimulating glucose release by liver


• A 51-amino-acid protein consisting of two amino acid chains linked by disulfide bonds

• Insulin is released when glucose levels exceed normal levels (70-110 mg/dl)

Insulin

http://www.chemistryexplained.com/images/chfa_02_img0437.jpg


• Insulin facilitates entry of glucose cells by binding to a membrane receptor

• The complex insulin-receptor make a specific carrier protein (GLUT4) available

• Once at the cell surface, GLUT4 facilitates the passive diffusion of circulating glucose down its concentration gradient into cells.

• Receptors for insulin are present in most cell membranes (insulin-dependant cells)

• Cells that lack insulin receptors are cells in the brain, kidneys, lining of the digestive tract and RBC (insulin-independent cells).

• Those cells can absorb and utilize glucose without insulin stimulation.

Effects of Insulin Binding to its receptors


Effects of Insulin

• Acceleration of glucose uptake as a result from an increase of the number of glucose carrier proteins

• Acceleration of glucose utilization and increased ATP production

• Stimulation of glycogen formation in the liver and muscle cells

• Inhibits glycogenolysis (break down of glycogen) and gluconeogenesis (glucose building)

• Stimulation of amino acid absorption and protein synthesis

• Stimulation of triglyceride formation in adipose tissue

• As a result glucose concentration in the blood decreases


• Released by alpha cells

• A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent

• it promotes:

• Glycogenolysis – the breakdown of glycogen to glucose in the liver and skeletal muscle

• Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates in the liver

• Release of glucose to the blood from liver cells

• breakdown of triglycerides in adipose tissue

Glucagon


• Structurally and functionally, they are two glands in one

• Adrenal medulla – neural tissue; part of the sympathetic nervous system

• Adrenal cortex - three layers of glandular tissue that synthesize and secrete corticosteroids

Adrenal (Suprarenal) Glands


Adrenal Cortex

• Synthesizes and releases steroid hormones called corticosteroids

• Different corticosteroids are produced in each of the three layers

• Zona glomerulosa – glomerulus- little ball. Secretes mineralocorticoids – main one aldosterone

• Zona fasciculata – glucocorticoids (chiefly cortisol)

• Zona reticularis – gonadocorticoids (chiefly androgens)


Zona fasciculata - Glucocorticoids (Cortisol/hydrocortisone)

• Main hormones secreted are the Cortisol/hydrocortisone and small amounts of corticosterone

• Glucocorticoids often called the body’s stress hormones

• While adrenaline is responsible for rapid metabolic responses the glucocorticoids are responsible for long-term stress:

• Glucocorticoids accelerate the rates of glucose synthesis and glycogen formation – especially in the liver

• Adipose tissue responds by releasing fatty acids into the blood and the tissues start to utilize fatty acids as source of energy - glucose-sparing effect (GH has similar effect and will be discussed later)

• Clucocorticoids also have anti-inflammatory effect – inhibit the activities of WBC (use?)


Control of glucocorticoids

Region Hormone Target Effect Hypothalamic regulatory hormone

Thyroid-stimulating hormone (TSH/ thyrotropin)

Thyroid gland Secretion of thyroid hormones (T3, T4)

Thyrotropin-releasing hormone (TRH)

Adrenocorticotropic hormone (ACTH)

Adrenal cortex (zona fasciculate)

Secretion of glucocorticoids (cortisole, corticosterone)

Corticotrophin-releasing hormone (CRH)


Diabetes Mellitus (DM)

• Two types:

• Type I results from the destruction of beta cells and the complete loss of insulin (hypoinsulinemia)

• Type II is the most common type (90%) and is a result of decrease sensitivity of cells to insulin (insulin resistance). Type II is accompanied by hyperinsulinemia (what is that? Why?).

• Type II is associated with excess weight gain and obesity but the mechanisms are unclear.

• Other reasons that were associated with type II diabetes: pregnancy, polycystic ovary disease, mutations in insulin receptors and others

Copyright © 2010 Pearson Education, Inc. Table 24.1

Type 1 and Type 2 Diabetes Mellitus


Diabetes Mellitus (DM) effects

• Increase in blood glucose due to diabetes causes

• Increase in glucose loss in urine

• Dehydration of cells – since glucose does not diffuse through cell membrane and there is an increase in osmotic pressure in the extracellualr fluid.

• In addition, the loss of glucose in the urine causes osmotic diuresis - decrease in water reabsorption in the kidney.

• The result is

• Polyuria – huge urine output and dehydration.

• Polydipsia – excessive thirst


Diabetes Mellitus (DM) effects

• Polyphagia – excessive hunger and food consumption because cells are starving

• Damage to blood vessels and poor blood supply to different tissues

• Increase use of lipids as a source of energy by the cells and increase release of keto bodies – ketosis and changes of blood pH (acidosis). That leads to increased respiratory rate


http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm


Hormones that control minerals and water

We will see the different glands that control:

Sodium – Adrenal gland

Which layer and what hormone group?

Calcium – Thyroid and parathyroid

Water - hypothalamus


Zona glomerulosa – Mineralocorticoids

• Aldosterone secretion is stimulated by:

• Rising blood levels of K+

• Low blood Na+

• Decreasing blood volume or pressure


• The mineralocorticoids are steroids that affect the electrolytes composition of the body extracellular fluids.

• Aldosterone – most important mineralocorticoid

• Maintains Na+ balance by reducing excretion of sodium from the body

• Stimulates re-absorption of Na+ by the kidneys

• Prevents the loss of Na+ by the kidneys, sweat glands, salivary glands and digestive system

• As a result of Na+ reabsorption there is also water reabsorption

• The retention of Na+ is accompanied by a loss of K+

Zona glomerulosa - Mineralocorticoids


Summary of the adrenal gland


What are the calcium functions in the body?

Provides structure for bones and teeth

Transmission of nerve impulses

Assists in muscle contraction

Part of blood clotting

Regulates hormones and enzymes (2nd messanger)


Protein hormones that control calcium

Thyroid gland – calcitonin

Parathyroid gland - PTH


Parathyroid Glands

• Tiny glands embedded in the posterior aspect of the thyroid

• Contain oxyphil cells (function unknown) and chief cells that secrete parathyroid hormone (PTH) or parathormone

• PTH—most important hormone in Ca2+ homeostasis


• PTH release increases Ca2+ in the blood:

• Stimulates osteoclasts to digest bone matrix

• Enhances the reabsorption of Ca2+ and the secretion of phosphate by the kidneys

• Increases absorption of Ca2+ by intestinal mucosal

• Rising Ca2+ in the blood inhibits PTH release

• The antagonist is the Calcitonin secreted by the thyroid gland

Effects of Parathyroid Hormone


• A peptide hormone produced by the parafollicular, or C cells

• Lowers blood calcium levels

• Antagonist to parathyroid hormone (PTH)

Calcitonin


• Calcitonin targets the skeleton, where it:

• Inhibits osteoclast activity (and thus bone resorption) and release of calcium from the bone matrix

• Stimulates calcium uptake and incorporation into the bone matrix

• Regulated by a humoral (calcium ion concentration in the blood) negative feedback mechanism

Calcitonin



Hormones that are involved in water balance

Anti diuretic hormone (ADH) – hypothalamus (stored in the neurohypophysis)

Aldosterone (where is it produces? What is the target organ?)

Atrial natriuretic peptide (ANP) - heart


Pituitary gland (Hypophysis)

• Pituitary gland – two-lobed organ that secretes nine major hormones

• Neurohypophysis – posterior lobe (neural tissue) and the infundibulum

• Receives, stores, and releases hormones from the hypothalamus

• Adenohypophysis – anterior lobe, made up of glandular tissue

• Synthesizes and secretes a number of hormones


Pituitary-Hypothalamic Relationships: Posterior Lobe

• Is a down growth of hypothalamic neural tissue

• Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)

• Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH)

• These hormones are transported to the posterior pituitary

• Stores antidiuretic hormone (ADH) and oxytocin

• ADH and oxytocin are released in response to nerve impulses

• Both use PIP-calcium second-messenger mechanism at their targets


Neurohypophysis hormones

Hormone Target Effect

Antidiuretic hormone (ADH)

Arginine vasopresin (AVP)

Kidneys Reabsorption of water,

elevation of blood volume and pressure (vasoconstriction)

Oxytocin (OT) Uterus, mammary glands (female)

Ductus deferens and prostate gland (male)

Labor contractions, milk ejection

Contractions of ductus deferens and prostate gland

Hormones that are produced in the hypothalamus and stored in the neurohypophysis


Water reabsorption and urine concentration

• Obligatory Water Reabsorption

• Is water movement that cannot be prevented

• Usually recovers 85% of filtrate produced

• Facultative Water Reabsorption

• Controls volume of water reabsorbed by ADH


ADH and urine volume and concentration• ADH is released by the posterior pituitary in response to increased

osmotic pressure (decreased water or increased solutes in blood).

• When ADH reaches the kidney, it increases the permeability of the epithelial linings to water, and water moves rapidly out of these segments, eventually into the blood, by osmosis (water is reabsorbed).

• Consequently, urine volume falls, and urine concentrates soluble wastes and other substances in minimal water. Concentrated urine minimizes loss of body fluids when dehydration is likely.

• If the osmotic pressure of the blood decreases, ADH is not released and water stays in the collecting duct, leaves as part of the urine.


Aldosterone and urine concentration

• Aldosterone is a steroid secreted by the adrenal cortex

• It is secreted when blood sodium falls or if blood potassium rises

• It is also secreted if BP drops (will be discussed later with the urinary system)

• Aldosterone secreted – increased tubular reabsorption of Na+ in exchange for secretion of K+ ions – water follow

• Net effect is that the body retains NaCl and water and urine volume reduced

• The retention of salt and water help to maintain blood pressure and volume


Atrial natriuretic peptide (ANP) and urine volume

• Secreted from the atrial myocardium in response to high BP

• Has 4 actions that result in the excretion of more salt and water in the urine:

• Dilate afferent arteriole and constricts efferent – increase GFR (more blood flow and higher GHP)

• Antagonized angiotensin-aldosterone mechanism by inhibiting both renin and aldosterone secretion

• Inhibits ADH

• Inhibits NaCl reabsorption by the collecting ducts


Hormones involved in Growth and metabolism

Growth hormone – anterior pituitary gland

Thyroid Hormones – hypothalamus, pituitary gland and thyroid


The anterior lobe• Is an out pocketing of the oral mucosa from epithelial tissue

• There is no direct neural contact with the hypothalamus

• Hormone production is regulated by the hypothalamus

• Regulatory factors from the hypothalamus arrive directly to the

adenohypophysis through the hypophyseal portal system

• Releasing hormones stimulate the synthesis and release of hormones

• Inhibiting hormones shut off the synthesis and release of hormones

• The hormones of the anterior pituitary (7) are called tropic/trophic hormones because they “turn on” other glands or organs


• Portal system - a system of blood vessels that begins and ends in capillaries. The blood, after passing through one capillary bed, is passing through a second capillary network.

• All blood entering the portal system will reach the target cells before returning to the general circulation

Hypophyseal portal system


Pituitary-Hypothalamic Relationships: anterior Lobe

• The hypophyseal portal system, consisting of:

• The primary capillary plexus in the infundibulum

• The hypophyseal portal veins

• The secondary capillary plexus


Tropic Hormones of the Anterior Pituitary


Normal Growth in Humans

• Growth is a continuous process that varies in rate, and depends on four factors

1. Growth hormone and several other hormones (for example – hormones that control calcium and glucose)

2. An adequate diet

3. Absence of chronic stress

4. Genetic potential for growth


Growth Hormone (GH) or somatotropin

• GH is an anabolic (tissue-building) hormone

• Stimulate most body cells to increase in size and divide by increasing protein synthesis

• Major target tissues are bone, cartilage and skeletal muscle

• GH release is regulated factors released by the hypothalamus:

• Growth hormone–releasing hormone (GHRH)

• Growth hormone–inhibiting hormone (GHIH) (somatostatin


Effects of Growth Hormone

• Growth Hormone has several distinct cellular effects

• Increases plasma glucose

• Increases bone and muscle growth

• Stimulates protein synthesis

• Stimulates liver to secrete IGFs

• IGFs stimulate cartilage growth


Growth Hormone (GH) or somatotropin

• The stimulation of growth by GH involves 2 mechanisms:

• The primary one is indirect and more understood:

• GH influence the liver, skeletal muscle, bone, and cartilage to release insulin-like growth factors (IGF)/somatomedins

• The IGF binds to specific receptors on cells and increase the uptake of amino acids and their incorporation into new proteins


Growth Hormone (GH) or somatotropin• Direct effects

• In ET and CT stimulate cell division and differentiation (the subsequent cell growth is mediated by IGF)

• In adipose tissue GH stimulates the breakdown of stored triglycerides by adipocytes and the release of fatty acids to the blood. That promotes the use of fatty acid for energy instead of the use of glucose (glucose-sparing effect)


Tissue Growth Requires not only GH and IGF

• GH and IGFs required for protein and cell division

• Thyroid hormone plays permissive role

• Insulin supports tissue growth (how?)

• adequate diet


Control of thyroid gland function

The control includes the following:

Hypothalamus – TRH

Pituitary gland - TSH


Anterior pituitary hormones

Region Hormone Target Effect Hypothalamic regulatory hormone

Thyroid-stimulating hormone (TSH/ thyrotropin)

Thyroid gland Secretion of thyroid hormones (T3, T4)

Thyrotropin-releasing hormone (TRH)

Adrenocorticotropic hormone (ACTH)

Adrenal cortex (zona fasciculate)

Secretion of glucocorticoids (cortisole, corticosterone)

Corticotrophin-releasing hormone (CRH)


• Thyroid hormone – major metabolic hormone

• Consists of two related iodine-containing compounds

• T4 – thyroxine; has two tyrosine molecules plus four bound iodine atoms

• T3 – triiodothyronine; has two tyrosines with three bound iodine atoms

Thyroid Hormone


Synthesis of Thyroid Hormone

• Thyroglobulin is synthesized by the follicular cells and released into the lumen

• Iodides (I–) are actively taken into the cell by membrane carrier proteins

• The iodide ions diffuse to the apical surface of the cells (these cells are facing towards…?), oxidized to iodine (I2) by the enzyme thyroid peroxidase and released to the colloid.

• Iodine attaches to tyrosine in the thyrogobulin, forming T1 (monoiodotyrosine, or MIT), and T2 (diiodotyrosine, or DIT)


Synthesis of Thyroid Hormone

• Iodinated tyrosines link together to form T3 and T4

• Coupling reaction

MIT + DIT T3 / triiodothyronine

DIT + DIT T4 / thyroxin (tetraiodothyronine)

• The colloid is then endocytosed and combined with a lysosome, where T3 (10%) and T4 (90%) are cleaved and diffuse into the bloodstream

• 75% of the T4 and 70% of the T3 are transported attached to thyroid-binding protein (TBGs) and the rest to a special albumin


Thyroid Hormones are Made from Iodine and Tyrosine

Figure 23-8


Thyroid Hormone

• Although the major thyroid hormone that is being produced is the T4 (90%) T3 is the one responsible for the TH effects

• Enzymes in the kidneys, liver and other tissues convert T4 to T3


Figure 18-11a The Thyroid Follicles

Folliclecavity

Thyroglobulin(contains T3 and T4)

FOLLICLE CAVITY

Endocytosis

Lysosomaldigestion

Thyroglobulin

Other amino acids

Tyrosine

Diffusion

DiffusionTSH-sensitiveion pump FOLLICLE CELL

CAPILLARY

Iodide (I–)

T4 & T3

TBG, transthryretin,or albumin

The synthesis, storage, and secretion of thyroid hormones.

Iodide(I+)

T4T3

Copyright © 2010 Pearson Education, Inc. Figure 16.9, step 7

To peripheral tissues

T3

T3

T3

T4

T4

Lysosome

Tyrosines (part of thyroglobulinmolecule)

T4

DIT (T2)Iodine

MIT (T1)

Thyro-globulincolloid

Iodide (I–)

RoughER

Capillary

Colloid

Colloid inlumen offollicle

Thyroid follicle cells

Iodinated tyrosines arelinked together to form T3

and T4.

Iodideis oxidizedto iodine.

Thyroglobulin colloid isendocytosed and combinedwith a lysosome.

Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream.

Iodide (I–) is trapped(actively transported in).

Thyroglobulin is synthesized anddischarged into the follicle lumen.

Iodine is attached to tyrosinein colloid, forming DIT and MIT.

Golgiapparatus

1

2

3

4

5

6

7


Thyroid Hormone and target cells

• Thyroid hormones influence almost every cell of the body

• Inside the cells they bind to receptors in one of 3 locations:

• In the cytoplasm – storage of thyroid hormones to be released if the intracellular levels decrease

• On the mitochondria surface – increase rate of ATP production

• In the nucleus – activate genes that control the synthesis of enzymes that involve with energy production and utilization (for example increase of production of sodium-potassim ATPase that uses ATP)


Functions of Thyroid Hormones

• Calorigenic Effect

• Cell consumes more energy resulting in increased

heat generation

• Is responsible for strong, immediate, and short-

lived increase in rate of cellular metabolism


Functions of Thyroid Hormones

Elevates rates of oxygen consumption and energy consumption; in children, may cause a rise in body temperature

Increases heart rate and force of contraction; generally results in a rise in blood pressure

Increases sensitivity to sympathetic stimulation Stimulates red blood cell formation and thus enhances oxygen

delivery Stimulates activity in other endocrine tissues (E, NE for

example) Accelerates turnover of minerals in bone Activate genes that code for enzymes that are involved in

glycolysis (Glucose oxidation) In children, essential to normal development of Skeletal,

muscular, and nervous systems

Copyright © 2010 Pearson Education, Inc. Figure 7-2 (1 of 2)

Anatomy Summary: Hormones

Copyright © 2010 Pearson Education, Inc. Figure 7-2 (2 of 2)

Anatomy Summary: Hormones

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Endocrine system