endocrine system and nutrition; nutrition and endocrine system

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Endocrine system and nutrition;Nutrition and endocrine system


Let’s define some more - Define 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?


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


Bloodstream


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


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


Let’s define some more - Define nutrients Nutrients are chemicals in foods that our bodies use for growth

and function Organic nutrients contain carbon, an essential component of all

living organisms Carbohydrates, lipids, proteins, vitamins

Inorganic nutrients: nutrients that do not contain carbon Minerals and water

Macronutrients are nutrients required in relatively large amounts Provide energy to our bodies Carbohydrates, lipids, proteins


• Two main classes

1.Amino acid-based hormones

Amino acid derivatives

• Structurally similar to amino acids

• Derivative of tyrosine : thyroid hormones catecholamines (Epinephrine, norepinephrin, dopamine),

• Derivative of tryptophan - melatonine.

Hormone structure - based on chemical structure


• Peptide hormones – 2 groups• Short polypeptides and small proteins – hormones

secreted by heart, thymus, digestive tract, pancreas, hypothalamus (ADH and OT) and anterior pituitary (ACTH, GH, MSH, PRL)

• Glycoproteins – consist more than 200 amino acids and have carbohydrate side chains.

• anterior pituitary (TSH, LH and FSH), kidneys (erythropoietin), reproductive organs (inhibin)

Hormone structure


2.Steroids (Lipid derivatives)

• Synthesized from cholesterol

• Gonadal and adrenocortical hormones

Hormone structure


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


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


• The hormone must interact with a specific receptor in order to affect the 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


Indirect effect – through G-protein and 2nd messenger


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• 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


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


• 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


Intracellular Receptors and Direct Gene Activation• Steroid hormones and thyroid hormone

1. Diffuse into their target cells and bind with intracellular receptors

2. Receptor-hormone complex enters the nucleus

3. Receptor-hormone complex binds to a specific region of DNA

4. This prompts DNA transcription to produce mRNA

5. The mRNA directs protein synthesis


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


What Are Carbohydrates?

One of the three macronutrients Important source of energy for all cells Preferred energy source for nerve cells Composed of carbon, hydrogen, oxygen Good sources: fruits, vegetables, grains Important component of the glycoprotein hormones

(gondotrophins, Thyroid-stimulating hormone, erythropoietin to name few)


Different types of carbohydrates

Simple carbohydrates Contain one or two molecules Commonly referred to as sugars

Monosaccharides contain one molecule Glucose, fructose, and galactose

Disaccharides contain two molecules Lactose, maltose, and sucrose


What Are Carbohydrates?

Glucose The most abundant

carbohydrate Produced by plants

through photosynthesis


Different types of carbohydrates - Complex carbohydrates

Oligosaccharides contain 3 to 10 monosaccharides Most polysaccharides consist of hundreds to thousands of

glucose molecules (Starch, glycogen, most fibers)


Complex Carbohydrates - Starch

Plants store carbohydrates as starch Amylose—straight chain of glucose Amylopectin—branched chain of glucose Resistant starch (fiber)—glucose molecules linked by

beta bonds are largely indigestible Sources: grains, legumes, fruits, vegetables


Complex Carbohydrates - glycogen

Storage form of glucose for animals (humans) Not found in food and therefore not a source of dietary

carbohydrate Stored in the liver and muscles


Complex Carbohydrates - fiber

Composed of long polysaccharide chains Dietary fibers are non-digestible parts of plants Functional fibers are non-digestible forms of

carbohydrates extracted from plants or manufactured in a laboratory and have known health benefits

Total fiber = Dietary fiber + Functional fiber


Complex Carbohydrates - Soluble fibers

Dissolve in water; viscous and gel-forming Fermentable, digested by intestinal bacteria Associated with risk reduction of cardiovascular

disease and type 2 diabetes Examples: pectin, gum, mucilage Found in citrus fruits, berries, oats, beans


Complex Carbohydrates – insoluble fibersDo not dissolve in water, nonviscousCannot be fermented by bacteria in the colonPromote regular bowel movements, alleviate

constipation, and reduce diverticulosis Examples: lignins, cellulose, hemicellulosesGood sources: whole grains, seeds, legumes, fruits,

and vegetables

ABC Video Whole Grains


The Role of Carbohydrates – Energy

Each gram of carbohydrate: 4 kcal Red blood cells use only glucose for energy Both carbohydrates and fats supply energy for daily

activities Glucose is especially important for energy during

exercise


The Role of Carbohydrates – prevent ketosis

Fat breakdown during fasting forms ketones Excess ketones increase blood acidity and cause

ketoacidosis Sufficient energy from carbohydrates prevents ketone

production as alternate energy source (will be discussed later in the course)

Fad Diets


The Role of Carbohydrates - Spare Protein

Gluconeogenesis occurs when a diet is deficient in carbohydrate

The body will make its own glucose from protein Amino acids from these proteins cannot be used to

make new cells, repair tissue damage, support the immune system, or perform any of their other functions


Complex Carbohydrates Have Health Benefits

Fiber May reduce the risk of colon cancer Helps prevent hemorrhoids, constipation, and other intestinal

problems May reduce the risk of diverticulosis May reduce the risk of heart disease May enhance weight loss May lower the risk of type 2 diabetes

Diverticulosis and Fiber


How Much Carbohydrate?

Recommended Dietary Allowance (RDA) is 130 grams/day to supply adequate glucose to the brain

Acceptable Macronutrient Distribution Range (AMDR) is 45% to 65% of daily calories

Focus on fiber-rich carbohydrate foods


Simple Carbohydrates

Diets high in simple sugars: Can cause tooth decay May increase “bad cholesterol” May decrease “good cholesterol” May contribute to obesity

ABC Video Sugar and Processed Food


Complex Carbohydrates

Most Americans eat too little complex carbohydrates

Enriched foods are foods in which nutrients that were lost during processing have been added back so the food meets a specified standard

Fortified foods have nutrients added that did not originally exist in the food (or existed in insignificant amounts)


Complex Carbohydrates

Adequate Intake (AI) for fiber 25 g per day for women 38 g per day for men, or 14 g of fiber for every 1,000 kcal per day

It is best to get fiber from food (also a source of vitamins and minerals)

An adequate fluid intake (at least 8 oz/day) with high-fiber diets is recommended


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


Endocrine organs: Pancreas 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


Pancreas and blood glucose levels

• Blood Glucose Levels are controlled 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


HOMEOSTASISDISTURBED

Rising bloodglucose levels

Beta cellssecreteinsulin.

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bloo

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ucos

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vels

Falli

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glu

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Falling bloodglucose level

HOMEOSTASISDISTURBED

Alpha cellssecrete

glucagon

HOMEOSTASISRESTORED

HOMEOSTASISRESTORED

Blood glucoselevels decrease

Blood glucose levels increase

Increased breakdown ofglycogen to glucose (inliver, skeletal muscle)

Increased breakdown of fat to fatty acids (inadipose tissue)

Increased synthesisand release of glucose(in liver)

HOMEOSTASISNormal bloodglucose levels(70-110 mg/dL)

Increased amino acidabsorption and proteinsynthesis

Increased triglyceridesynthesis in adiposetissue

Increased conversionof glucose to glycogen

Increased rate ofglucose utilization andATP generation

Increased rate ofglucose transport intotarget cell


• 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 (what does it mean?)

• 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


Other hormones that control glucose levels

Glucocorticoids


• Adrenal glands – paired, pyramid-shaped organs atop the kidneys

• 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 glumerulosa – Mineralocorticoids

• Aldosterone secretion is stimulated by:• Rising blood levels of K+

• Low blood Na+

• Decreasing blood volume or pressure• Effects will be discussed in details with the

urinary system


Zona fasciculata - Glucocorticoids (Cortisol/hydrocortisone)

• This adrenal layer responds to ACTH (which endocrine glands secretes ACTH?)

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

• 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?)


Zona reticularis Gonadocorticoids (Sex Hormones)

• Most gonadocorticoids secreted are androgens (male sex hormones), and the most important one is testosterone

• Androgens can be converted into estrogens after menopause

• Both hormones from the kidney origin do not effect sexual characteristics


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


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


Carbohydrate metabolism disorders


Hypoglycemia

Low blood glucose may cause shakiness, sweating,

anxiety, weakness

Reactive hypoglycemia: pancreas secretes too much

insulin after a high-carbohydrate meal

Fasting hypoglycemia: pancreas produces too much

insulin, even when someone has not eaten


Blood glucose levels in normal and hypoglycemia


Lactose Intolerance

Insufficient enzyme lactase to digest the lactose-

containing foods

GI symptoms: gas, cramping, diarrhea

Variations in extent of intolerance

Not to be confused with milk allergy

Need alternate sources of calcium

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