Endocrine system
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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

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Endocrine system

Endocrine system


Hormone

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

Endocrine versus Nervous system

  • Both use chemical communication

  • Both are being regulated primarily by negative feedback

  • Released in synapse

  • Close to target cells

  • Signal to release by action potential

  • Short live effect

  • Crisis management

Neurotransmitters

Hormones

  • Released to bloodstream

  • Can be distant from target cells

  • Different types of signal

  • Long term effect

  • Ongoing processes


Intercellular communication types

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

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

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

  • 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

  • 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

Classes of Hormones – by chemical structure

  • Hormones can be divided into three groups

    • Amino acid derivatives

    • Peptide hormones

    • Lipid derivatives


Amino acid derivatives

Amino Acid Derivatives

Derivatives of Tyrosine:

Thyroid hormones

Catecholamines

Epinephrine, norepinephrine

Derivatives of Tryptophan:

Dopamine, serotonin, melatonin


Peptide hormones

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 hormones1

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 aminoacids) 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

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

A Structural Classification of Hormones


Distribution of hormones in bloodstream

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 bloodstream1

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


Hormones classification

Hormones: Classification

Table 7-1


Target cell specificity

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

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

Target Cell Activation

  • Hormone exert their effects on target cells at very low bloodconcentrations (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


Receptors number on target cell

Receptors number on target cell

  • 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 for hormones are located

Receptors for hormones are located:

  • In the cell membranes of target cells

  • In the cytoplasm or nucleus


Mechanisms of hormone action

Mechanisms of Hormone Action

  • Two mechanisms, depending on their chemical nature

    • 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

    • Lipid-soluble hormones (steroid and thyroid hormones)

      • Act on intracellular receptors that directly activate genes


Receptors on the cell membrane

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


Endocrine system

Links the first

messenger

(hormone) and the

second messenger

Hormone

Protein

receptor

G protein

(inactive)

G protein

activated

The actions of second messengers for hormones that bind to

receptors in the plasma membrane

Effects on Ca2+ Levels

Effects on cAMP Levels

Some G proteins use Ca2+ as a second

messenger.

Many G proteins, once activated, exert their effects by changing the

concentration of cyclic-AMP, which acts as the second messenger within

the cell.

Ca2+

Hormone

Hormone

Hormone

Protein

receptor

Protein

receptor

Protein

receptor

Enhanced

breakdown

of cAMP

Increased

production

of cAMP

G protein

activated

G protein

activated

G protein

activated

Opening

of Ca2+

channels

Release of

stored Ca2+

from ER

or SER

Acts as

second

messenger

cAMP

cAMP

ATP

AMP

Ca2+

Ca2+

Ca2+ acts as

second messenger

Ca2+

Reduced

enzyme

activity

Calmodulin

Opens ion

channels

Activates

enzymes

Activates

enzymes

If levels of cAMP increase,

enzymes may be activated

or ion channels may be

opened, accelerating the

metabolic activity of the

cell.

In some instances, G protein

activation results in decreased

levels of cAMP in the

cytoplasm. This decrease has

an inhibitory effect on the cell.

The calcium ions themselves serve as

messengers, generally in combination

with an intracellular protein called

calmodulin.

Figure 16.2 1


Receptors on the cell membrane1

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

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


Endocrine system

Extracellular fluid

1

Hormone (1st messenger)binds receptor.

Adenylate cyclase

G protein (GS)

5

cAMP acti-vates proteinkinases.

Receptor

Activeproteinkinase

GDP

Inactiveprotein kinase

2

3

4

Receptoractivates Gprotein (GS).

G proteinactivatesadenylatecyclase.

Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).

Hormones thatact via cAMPmechanisms:

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

GlucagonPTHTSHCalcitonin

EpinephrineACTHFSHLH

Cytoplasm

Figure 16.2, step 5


Amino acid based hormone action pip calcium

Amino Acid-Based Hormone Action: PIP-Calcium

  • 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 mechanism

Amino Acid-Based Hormone Action: PIP Mechanism

Extracellular fluid

Hormone

DAG

1

4

5

Active

protein

kinase C

2

3

PIP2

GTP

GTP

Receptor

Gq

Inactive

protein

kinase C

GDP

GTP

IP3

Phospholipase C

Catecholamines

TRH

ADH

GnRH

Oxytocin

Triggers responses

of target cell

5

Endoplasmic

reticulum

6

Cytoplasm

Ca2+

Ca2+- calmodulin

Figure 16.3


Steroid hormones action

Steroid Hormones: Action

1

Most hydrophobic steroids are bound to

plasma protein carriers. Only unbound

hormones can diffuse into the target cell.

Blood

vessel

Steroid

hormone

Cell surface receptor

2a

Rapid responses

1

2

Steroid hormone receptors are in the

cytoplasm or nucleus.

2

Protein

carrier

Nucleus

2a

Some steroid hormones also bind to

membrane receptors that use second

messenger systems to create rapid

cellular responses.

Cytoplasmic

receptor

Nuclear

receptor

DNA

Interstitial

fluid

3

The receptor-hormone complex binds to

DNA and activates or represses one or

more genes.

3

Endoplasmic

reticulum

Transcription

produces mRNA

Cell

membrane

4

Activated genes create new mRNA that

moves back to the cytoplasm.

5

4

New

proteins

Translation

5

Translation produces new proteins

for cell processes.

Figure 7-7, steps 1–5


Endocrine system

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


How will we approach the endocrine system

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

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

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 GHinhibiting 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

Pancreas


How does the body control blood glucose levels

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


Insulin

Insulin

  • 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)

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


Effects of insulin binding to its receptors

Effects of Insulin Binding to its receptors

  • 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

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


Glucagon

Glucagon

  • Released by alpha cells

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

  • 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


Adrenal suprarenal glands

Adrenal (Suprarenal) Glands

  • 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 cortex

Adrenal Cortex

  • Synthesizes and releases steroid hormones called corticosteroids

  • Different corticosteroids are produced in each of the three layers

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

    • Zonafasciculata– glucocorticoids (chiefly cortisol)

    • Zonareticularis – gonadocorticoids (chiefly androgens)


Zona fasciculata glucocorticoids cortisol hydrocortisone

Zonafasciculata - 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

Control of glucocorticoids


Diabetes mellitus dm

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


Type 1 and type 2 diabetes mellitus

Type 1 and Type 2 Diabetes Mellitus

Table 24.1


Diabetes mellitus dm effects

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 effects1

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


Endocrine system

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


Hormones that control minerals and water

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

Zonaglomerulosa– Mineralocorticoids

  • Aldosterone secretion is stimulated by:

    • Rising blood levels of K+

    • Low blood Na+

    • Decreasing blood volume or pressure


Zona glomerulosa mineralocorticoids1

Zonaglomerulosa- Mineralocorticoids

  • 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+


Summary of the adrenal gland

Summary of the adrenal gland


What are the calcium functions in the body

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 (2ndmessanger)


Protein hormones that control calcium

Protein hormones that control calcium

  • Thyroid gland – calcitonin

  • Parathyroid gland - PTH


Parathyroid glands

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


Effects of parathyroid hormone

Effects of Parathyroid Hormone

  • 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


Calcitonin

Calcitonin

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

  • Lowers blood calcium levels

  • Antagonist to parathyroid hormone (PTH)


Calcitonin1

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


Hormones that are involved in water balance

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 (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

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

Neurohypophysis hormones

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


Water reabsorption and urine concentration

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 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 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

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

Hormones involved in Growth and metabolism

  • Growth hormone – anterior pituitary gland

  • Thyroid Hormones – hypothalamus, pituitary gland and thyroid


The anterior lobe

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


Hypophyseal portal system

Hypophyseal portal system

  • 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


Pituitary hypothalamic relationships anterior lobe

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


Endocrine system

Tropic Hormones of the Anterior Pituitary


Normal growth in humans

Normal Growth in Humans

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

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

    • An adequate diet

    • Absence of chronic stress

    • Genetic potential for growth


Growth hormone gh or somatotropin

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

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 somatotropin1

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 somatotropin2

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

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

Control of thyroid gland function

  • The control includes the following:

  • Hypothalamus – TRH

  • Pituitary gland - TSH


Anterior pituitary hormones

Anterior pituitary hormones


Thyroid hormone

Thyroid Hormone

  • 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


Synthesis of 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 hormone1

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

Thyroid Hormones are Made from Iodine and Tyrosine

Figure 23-8


Thyroid hormone1

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

Figure 18-11a The Thyroid Follicles

Follicle

cavity

Thyroglobulin

(contains T3 and T4)

FOLLICLE CAVITY

Endocytosis

Thyroglobulin

Iodide

(I+)

Lysosomal

digestion

Other amino acids

Tyrosine

T4

T3

Diffusion

Diffusion

TSH-

sensitive

ion pump

FOLLICLE CELL

CAPILLARY

Iodide (I–)

TBG, transthryretin,

or albumin

T4 & T3

The synthesis, storage, and secretion of thyroid hormones.


Endocrine system

Thyroid follicle cells

Colloid

1

Thyroglobulin is synthesized anddischarged into the follicle lumen.

Tyrosines (part of thyroglobulinmolecule)

Capillary

4

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

Golgiapparatus

RoughER

Thyro-globulincolloid

Iodine

DIT (T2)

MIT (T1)

3

Iodideis oxidizedto iodine.

2

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

Iodide (I–)

T4

5

Iodinated tyrosines arelinked together to form T3and T4.

T3

Lysosome

T4

6

Thyroglobulin colloid isendocytosed and combinedwith a lysosome.

T3

7

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

Colloid inlumen offollicle

T4

T3

To peripheral tissues

Figure 16.9, step 7


Thyroid hormone and target cells

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

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 hormones1

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


Anatomy summary hormones

Anatomy Summary: Hormones

Figure 7-2 (1 of 2)


Anatomy summary hormones1

Anatomy Summary: Hormones

Figure 7-2 (2 of 2)


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