The Endocrine System

Chapter 17

Intercellular Communication

Cell Target Cell

Cell

Cell Target Cell

Target CellNeuron

Hormone

Hormone

Hormone Hormone

Hormone

Hormone

Hormone

Endocrine

Paracrine

Autocrine

BloodNeuroendocrine

Blood

Interstitial Fluid

Interstitial Fluid

The endocrine system consists of the ductless glands.

• They are not connected anatomically. These glands secrete hormones into the blood. A hormone travels in the blood, signaling to distant target cells.

• Neurosecretory neurons release neurohormones. They are also distributed by the blood to target cells.

• Target cells are specific for each hormone or neurohormone. It is specific, as these cells have receptors that uniquely bind to a specific chemical messenger.

The endocrine and nervous systems are two regulatory systems of the body.

• The endocrine system mainly controls activities that require longer duration. This system has several overall functions.

• It regulates organic metabolism and water/electrolyte balance. It also induces adaptive changes to deal with stress. The endocrine system promotes smooth, sequential growth and development.

• Some hormones control reproduction while another one regulates red blood cell production. Some hormones regulate circulatory and digestive functions.

• A tropic hormone regulates the secretions of another endocrine gland. Tropic hormones are secreted by the anterior pituitary gland.

• Peptide & Protein Hormones • Steroid Hormones• Amine Hormones

Classes of Hormones

Chemical Classification of Hormones

• Amine hormones are derived from tyrosine or tryptophan• Include NE, Epi, thyroxine, melatonin

• Polypeptide/protein hormones are chains of amino acids• Include ADH, GH, insulin, oxytocin, glucagon,

ACTH, PTH• Glycoproteins

• Long polypeptide bound to a carbohydrate group• Include LH, FSH, TSH, hCG

• Steroids are lipids derived from cholesterol• Include testosterone, estrogen, progesterone &

cortisol

11-7

Hypothalamus

Anterior pituitary

Posterior pituitary

Thyroid

Pancreas

Liver

Parathyroid

• TRH, GnRH, CRH GHRH, Somatostatin,

• ACTH, TSH, FSH, LH, PRL, GH

• Oxytocin, ADH

• Calcitonin

Insulin,Glucagon, Somatostatin

Somatomedin C (IGF-1)

• PTH

Placenta

Kidney

Heart

G.I. tract

Adipocyte

• HCG, HCS or HPL

• Renin

ANP

Gastrin, CCK, Secretin, GIP, Somatostatin, GLP-1

•Leptin

Gland/Tissue Hormones Gland/Tissue Hormones

Peptide & Protein Hormones

Adrenal Cortex

Testes

Ovaries

Corpus Luteum

Placenta

Kidney

• Cortisol, Aldosterone, Androgens • Testosterone

• Estrogens, Progesterone

• Estrogens, Progesterone

• Estrogens, Progesterone

• 1,25-Dihydroxycholecalciferol

Gland/Tissue Hormones

Steroid Hormones

Amine Hormones

Hypothalamus

Thyroid

Adrenal medulla

• Dopamine

• T3, T4

• NE, EPI

Gland/Tissue Hormones

The mechanisms of hormone synthesis, storage, and secretion vary according to the class of hormone.

• Peptide hormones have precursors called preprohormones. They are made on ribosomes of the ER. In the Golgi complex they are converted to prohormones and, finally, active hormones. The Golgi complex concentrates these hormone into secretory vesicles.

• These hormones are released from endocrine cells by exocytosis. • Cholesterol is the common precursor for all steroid hormones. A

series of enzymatic steps modify this molecule into a different hormone in a specific endocrine cell. Only the precursor (cholesterol) is stored. The lipid-soluble hormone is not stored.

• The amine hormones are made from tyrosine.

All hormones are transported in the blood. However, they are not transported in the same way.

• Hydrophilic (water soluble) hormones are dissolved in the plasma. Most lipophilic (lipid soluble) hormones are bound reversibly to plasma proteins. These hormones are released by these proteins when they actively signal target cells.

• Hormones generally produce their effect by altering intracellular proteins.

• Hydrophilic hormones bind to receptors on the surface of target cells. Lipophilic hormones pass through target cell membranes and bind to receptors inside the target cell.

• A few hydrophilic hormones alter the permeability of the target cell’s membrane.

A hydrophilic hormone usually activates second-messenger systems.

• It binds to the target cell surface. This activates an intermediate G protein. This activates adenyl cyclase which converts intracellular ATP to cyclic AMP. Cyclic AMP triggers steps that alter the activity of a protein which is often an enzyme. This produces a physiological response in the target cell.

• A lipophilic hormone stimulates a gene, promoting protein synthesis.• This kind of hormone passes through the target cell membrane.

It binds with a receptor that binds to DNA. This turns on a gene. This gene makes RNA which makes a specific protein at the ribosome. This hormone changes the physiological response in the target cell.

• Compared to neural activity, the action of either class of hormone is usually slow and prolonged. Hormone actions are greatly amplified at the target cell. Activation of one receptor can activate many proteins.

Adenylate Cyclase-cAMP• Polypeptide or glycoprotein

hormone binds to receptor protein causing dissociation of subunit from G-protein complex.

• G-protein subunit binds to and activates adenylate cyclase.

• ATP cAMP + PPi • cAMP attaches to the inhibitory

subunit of protein kinase.• Inhibitory subunit dissociates

and activates protein kinase.• Phosphorylates enzymes within

the cell to produce hormone’s effects.

• Modulates activity of enzymes present in the cell.

• Alters metabolism of the cell.• cAMP inactivated by

phosphodiesterase.

Hormones That Bind to Nuclear Receptor Proteins• Lipophilic steroid and thyroid hormones

dissociate from carrier proteins.• Diffuse through the target plasma

membrane.• Steroid receptors are located in cytoplasm

and in the nucleus.• Function within cell to activate genetic

transcription.• Messenger RNA directs synthesis of

specific enzyme proteins that change metabolism.

• Each nuclear hormone receptor has 2 regions:• A ligand (hormone)-binding domain.• DNA-binding domain.

• Receptor must be activated by binding to hormone before binding to specific region of DNA called HRE (hormone responsive element).• Located adjacent to gene that will be

transcribed.

Other effects on hormone activity include:

• The concentration of a hormone in the blood is subject to control. It varies according to homeostatic need.

• The availability of a hormone to its receptor depends on the hormone’s rate of secretion, its rate of metabolic activation, the extend of its binding to plasma proteins if it is lipophilic, and its removal from the blood. Removal can be by metabolic inactivation or urinary excretion.

• Negative feedback maintains the plasma concentration of a hormone at a needed level. When a hormone’s concentration falls below a certain set point, the gland increases the secretion of the hormone. When the hormone’s level is above the set point, the secretion decreases.

• Many endocrine control systems involve neuroendocrine reflexes. Neural input to a gland regulates the gland’s secretion.

• The secretion rate of many hormones varies by a diurnal or circadian rhythm.

Endocrine disorders result from the hyposecretion or hypersecretion of a hormone.

• Factors producing hyposecretion include heredity, dietary deficiency, immunologic factors, and disease processes. Hyposecretion can be primary or secondary (due to the deficiency of the hormone’s tropic hormone).

• Replacement therapy of a hormone can often successfully treat the conditions from hyposecretion.

• Hypersecretion of a hormone can also be primary or secondary. Factors producing hypersecretion include tumors on the endocrine gland and immunologic factors.

• Endocrine dysfunction can also arise from the unresponsiveness of target cells to a hormone.

Table 17-1a, p. 533

Table 17-1b, p. 534

Table 17-1c, p. 534

Table 17-1d, p. 535

Table 17-1e, p. 535

The pituitary gland is a small structure at the base of the brain.

• The posterior lobe is the neurohypophysis. It is composed of nervous tissue. The anterior lobe is the adenohypophysis. It is glandular tissue.

• The posterior lobe and the hypothalamus act as a unit to secrete vasopressin and oxytocin. The axons of the hypothalamus pass from the brain into capillaries in the posterior lobe.

• The posterior lobe does not produce vasopressin and oxytocin. They are produced by hypothalamic neurons. They are stored in neuron terminals in the posterior lobe.

• Vasopressin (ADH) signals the kidneys to retain water. It also signals the smooth muscle in the walls of arterioles. Its main role is regulating water balance.

The anterior pituitary secretes six hormones. Many are tropic.

• By a vascular network with the hypothalamus, each anterior pituitary hormone is secreted through signaling by a releasing hormone from this region of the brain.

• The thyroid-stimulating hormone (TSH) stimulates the secretion and growth of the thyroid gland.

• The adrenocorticotropic hormone (ACTH) stimulates the growth and secretion of hormones from the adrenal cortex.

• The follicle-stimulating hormone (FSH) stimulates growth and development of the ovarian follicles in females and sperm production in males.

• The luteinizing hormone (LH) stimulates ovulation and luteinization (female) and stimulates testosterone secretion in the male.

• Prolactin enhances breast development in females.

Fig. 17-6a, p. 539

Hypothalamus

Anterior pituitary

Posterior pituitary

TSH

Thyroidgland

Thyroid hormone(T3 and T4)

Metabolic rate

ACTH

Adrenalcortex

Cortisol

Metabolic actions;stress response

Prolactin

Mammaryglands

Breast growth and milk secretion

Fig. 17-6b, p. 539

Hypothalamus

Anterior pituitary

Posterior pituitary

TSH ACTHGrowth hormone

Liver

Somatomedins

Many tissues

Metabolicactions

Bone Soft tissues

Growth

or

Fig. 17-6c, p. 539

Hypothalamus

Anterior pituitary

Posterior pituitary

TSH ACTHGrowth hormone

LH FSH

Gonads (ovaries in females, testes in males)

Sex hormone secretion(estrogen andprogesterone in females,testosterone in males)

Gamete production(ova in females,sperm in males)

Hypothalamic releasing and inhibiting hormones regulate anterior pituitary hormone secretion.

• TRH stimulates the release of TSH.• CRH stimulates the release of ACTH.• GnRH stimulates the release of FSH and LH.• GHRH stimulates the release of the growth

hormone.• GHIH inhibits the release of the growth hormone and

TSH.• PRH stimulates the release of prolactin.• PIH inhibits the release of prolactin.• A hypothalamic hormone controls the output of an

anterior pituitary hormone. The tropic hormone regulates the secretion of the target endocrine gland’s hormone.

Table 17-2, p. 540

The hypothalamic regulatory hormones reach the anterior pituitary by a vascular link.

• This is a capillary to capillary connection, the hypothalamic-hypophyseal portal system. Blood is this system carries hypothalamic signals to the anterior pituitary.

• Regulation of the secretion of the hypothalamic hormones depends on numerous inputs. Their complete regulation is not well understood.

• Target gland hormones inhibit hypothalamic and anterior pituitary hormone secretion via negative feedback.

• For example, a rise in cortisol from the adrenal cortex can feed back and reduce CRH secretion (hypothalamus) and the sensitivity of the ACTH secreting cells (anterior pituitary) to CRH.

• If cortisol falls in the blood, the direction of the other responses is reversed.

Fig. 17-8, p. 541

Hypothalamus

Anterior pituitary

Posterior pituitary

Neurosecretoryneurons

Systemic arterial inflow

Hypothalamic-hypophysealportal system

Systemvenousoutflow

= Hypophysiotropic Hormones = Anterior pituitary hormone

The endocrine system controls growth.• Growth is signaled by the growth hormone. There are other factors that

influence growth.• Growth capacity is genetically determined. Adequate diet, freedom from

chronic disease and stress, and normal levels of other growth-influencing hormones are other factors.

• The growth hormone does not play a role in fetal development. In children there is a postnatal growth spurt. The growth hormone may play a role in the later-occurring pubertal growth spurt. Androgens also contribute at this time.

The growth hormone has metabolic effects.

• It mobilizes fat stores (lipolytic) as a major energy source while conserving glucose for glucose-dependent tissues. This metabolic action is unrelated to growth.

• The growth hormone promotes growth by signaling an increase in the number of cells and size of cells in target organs. It stimulates the uptake of amino acids and protein synthesis in target cells.

• The growth hormone stimulates growth in the length and thickness of long bones.

• It stimulates the lengthening of bones at the epiphyseal plate. It stimulates osteoblast activity and the proliferation of epiphyseal cartilage. New bone tissue replaces cartilage in this region.

• It stimulates bone thickness by activating osteoblasts under the periosteum.

Fig. 17-6b, p. 539

Hypothalamus

Anterior pituitary

Posterior pituitary

TSH ACTHGrowth hormone

Liver

Somatomedins

Many tissues

Metabolicactions

Bone Soft tissues

Growth

or

The growth hormone exerts its effects indirectly by stimulating somatomedins.

• These substances are also called insulin-like growth factors. They are stimulated by the growth hormone and mediate most of the growth-promoting effects of the hormone.

• The main source of these factors is the liver. Their production depends on adequate nutrition. Their production is also related to age.

• The secretion of the growth hormone is regulated by GHRH and GHIH.

• Many factors influence the secretion of the growth hormone. It increases one hour after a deep sleep. Exercise can increase the secretion of the growth hormone. An abundance of amino acids and hypoglycemia increase its release.

Fig. 17-10, p. 545

Exercise, stress, blood glucose

Blood amino acids,Blood fatty acids

Hypothalamus Diurnalrhythm

Growth hormone–releasing hormone(GHRH)

Growth hormone–inhibiting hormone(GHIH)

Anterior pituitary

Growth hormone

Liver

Somatomedins

Metabolic actionsunrelated to growth: fat breakdown ( blood fatty acids)

glucose uptake by muscles ( blood glucose)

Growth-promoting actions: cell division protein synthesis ( blood amino acids) bone growth

A deficiency or excess of the growth hormone changes growth patterns.

• A hyposecretion produces dwarfism in a child. In Laron dwarfism, tissues fail to respond to the growth hormone.

• In adults a growth hormone deficiency reduces muscle mass and strength.• A hypersecretion of the growth hormone produces gigantism in the child. • If hypersecretion occurs after the epiphyseal plates have closed,

acromegaly develops. Only certain bones are affected. • Other hormones in addition to the growth hormone are essential for normal

growth. The thyroid hormone is essential for growth. Insulin is a growth promoter. Androgens play a role in a pubertal growth spurt.

The pineal gland is a small structure in the brain.

• It secretes the hormone melatonin. It helps keep the body’s circadian rhythms in synchrony with the light-dark cycle.

• The suprachiasmatic nucleus (SCN) has a major role in establishing many of the body’s daily rhythms.

• It secretes clock proteins. Cyclic changes in their concentration changes the neural output from the SCN.

• The SCN works in conjunction with the pineal gland and pineal gland to regulate circadian rhythms.

• Daily changes in light intensity is the major environmental factor used to adjust the SCN master clock.

• Melatonin has other functions not related to circadian timekeeping. It accomplishes natural sleep without hypnosis (side effects). It inhibits hormones that stimulate reproductive activity. It is also an effective antioxidant.

The thyroid gland consists of two lobes of endocrine tissue.

• It lies over the trachea, below the larynx.• Its follicular cells store colloid. Thyroglobulin

(TGB) is the main constituent of this colloid. The follicular cells produce two hormones, T4 and T3. These two hormones are collectively the thyroid hormone. It regulates overall basal metabolic rate.

• C cells between the follicular cells secrete calcitonin. It plays a role in calcium metabolism.

• Tyrosine and iodine are the ingredients for the thyroid hormone. The thyroid hormone synthesis occurs on the thyroglobulin molecules in the colloid.

Fig. 17-14, p. 549

BloodThyroid follicular cell

*Endoplasmic reticulum/Golgi complex

Colloid

TGB = Thyroglobulin I = Iodine MIT = Monoiodotyrosine

DIT = Di-iodotyrosine T3 = Tri-iodothyronine T4 = Tetraiodothyronine (thyroxine)

Lysosome

Thyroid hormone synthesis and storage occurs through a series of steps.

• Tyrosine is incorporated into TGB. This is transported into the colloid by exocytosis. Iodine is transported into the colloid by follicular cells.

• The attachment of one iodine to tyrosine produces MIT.• The attachment of two iodines to tyrosine produces DIT.• The coupling of two DITs produces T4.• The coupling of one MIT to two DITS produces T3.• Thyroid follicular cells engulf a part of TGB-containing colloid by

phagocytosis. • Lysosomes attack the engulfed vesicle and split the iodinated products from

TGB.• T4 and T3 reach the blood by diffusion.• The deiodination of T4 and T3 free the iodine for recycling.• The thyroid hormone is highly lipophilic. It binds to several plasma

proteins.

Most of the T4 is converted to T3 outside the thyroid. The thyroid hormone has many metabolic effects.

• T4 loses one of it iodines in the liver or kidney. • The hormone increases the body’s overall basal metabolic effect. It

regulates the body’s use of oxygen and is calorigenic (heat-producing).

• Large amounts of the secreted hormone convert glycogen into glucose and stimulates protein degradation.

• This hormone also has sympathomimetic effects, increasing target cells’ responsiveness to epinephrine and norepinephrine.

• It increases heart rate and the force of heart contraction.• It also stimulates growth hormone secretion and promotes the

effect of this hormone on increased protein synthesis.

Fig. 17-15, p. 551

Stress Cold in infants

Hypothalamus

Thyrotropin-releasinghormone (TRH)

Anterior pituitary

Thyroid-stimulatinghormone (TSH)

Thyroid gland

Thyroid hormone(T3 and T4)

Metabolic rate and heat production;enhancement of growth and CNS development; enhancement of sympathetic activity

The secretion of the thyroid hormone is regulated by the hypothalamus-pituitary-thyroid axis.

• TSH from the anterior pituitary stimulates the release of the thyroid hormone. TSH also maintains the structural integrity of the thyroid gland.

• TRH from the hypothalamus turns on TSH secretion. An increase in the thyroid hormone feeds back to decrease TSH secretion (negative feedback).

• TRH secretion is increased only by exposure to the cold in newborn infants.

Imbalances in the thyroid hormone cause changes in development.• Hypothyroidism produces myxedema in the adult. From birth a

deficiency of the hormone produces cretinism. Causes of these conditions include deficiency of TRH, TSH, or the thyroid hormone. A deficiency of iodine in the diet can also be a cause.

• Symptoms include a lowered basal metabolic rate, excessive weight gain, bradycardia, cold intolerance and the quick onset of fatigue.

• Grave’s disease is the most common cause of hyperthyroidism. It is an autoimmune disease. Symptoms include an elevated metabolic rate, high heart rate, heat intolerance and exophthalmos.

• A goiter develops when the thyroid gland is overstimulated. Hypothyroidism leads to high levels of TSH due to only a small amount of negative feedback. TSH acts on the follicular cells to increase their size and number.

• A goiter can develop in Grave’s disease due to an increase in thyroid-stimulating immunoglobulin (TSI).

Fig. 17-16, p. 551

Thyroid-stimulatingimmunoglobulin (TSI)

Anterior pituitary

No TSH

(No stimulation)

Thyroid gland

Thyroid hormone

There are two adrenal glands.• Each is embedded in a capsule of fat on top of each kidney.• The outer adrenal cortex of each gland secretes several steroid

hormones. The inner adrenal medulla of each gland secretes epinephrine and norepinephrine.

• The adrenal cortex consists of three different zones. Each secretes a different family of hormones.

• One of these zones secretes the mineralocorticoids. The mineralocorticoids (e.g., aldosterone) signal the kidneys (distal tubule and collecting duct) to retain sodium (plus water) and eliminate potassium. Aldosterone secretion is increased by activation of the renin-angiotensin-aldosterone system.

Fig. 17-20, p. 555

Stress Diurnal rhythm

Hypothalamus

Corticotropin-releasinghormone (CRH)

Anterior pituitary

Adrenocorticotropichormone (ACTH)

Adrenal cortex

Cortisol

Blood glucose(by stimulating gluconeogenesisand inhibiting glucose uptake)Blood amino acids(by stimulating protein degradation)Blood fatty acids(by stimulating lipolysis)

Metabolic fuelsand building blocksavailable to helpresist stress

One of the zones in the adrenal cortex secretes the glucocorticoids.

• The glucocorticoids (mainly cortisol) stimulate gluconeogenesis. This is the conversion of amino acids into carbohydrates, occurring mainly in the liver.

• Cortisol also facilitates the inhibition of glucose uptake, stimulates protein degradation, and promotes lipolysis.

• Cortisol plays a major role in the adaptation to stress. • Noxious stimuli that can produce this include physical, chemical,

physiologic, psychological, emotional, and social sources. An increased concentration of glucose in the blood is major response to all of these.

• Pharmacologic levels of cortisol can have anti-inflammatory and immunosuppressive effects. This can be used to treat rheumatoid arthritis or allergies. Long-term use of this treatment can produce unwanted side effects.

The secretion of cortisol is regulated by the hypothalamus-pituitary-adrenal cortex axis.

• ACTH from the anterior pituitary stimulates the secretion of cortisol from the adrenal cortex. ACTH secretion is triggered by CRH from the hypothalamus.

• Negative feedback from cortisol in the blood to the hypothalamus and the anterior pituitary regulate the level of cortisol in the blood.

• Increased output of CRH and ACTH increases in response to stress.

• Cortisol secretion also varies by a diurnal rhythm.

A third zone in the adrenal cortex secretes androgens or estrogens.

• Both are produced in either sex.• Usually they are not abundant enough to be powerful in

either sex. The androgens have masculinizing effects. • The androgen DHEA can have an effect in females who

otherwise lack androgens.

• ACTH controls adrenal androgen secretion.

The adrenal cortex may secrete too much or too little of its hormones.

• Primary hyperaldosteronism is Conn’s syndrome.• The secondary hyperaldosteronism is due to the high activity of the

renin-angiotensin mechanism.• Excessive cortisol secretion (Cushing’s syndrome) can be due to

increased amounts of CRH or ACTH, adrenal tumors, or ACTH-secreting tumors. The main symptom of this condition is excessive gluconeogenesis.

• Adrenal androgen hypersecretion produces adrenogenital syndrome. It manifests with different effects depending of the biological sex and age of the subject.

• Primary adrenocortical insufficiency is known as Addison’s disease. This is usually an autoimmune disease. The secondary cause of this insufficiency occurs because of an abnormality of the pituitary or hypothalamus.

• Symptoms of Addison’s disease include: hypotension, hypoglycemia, potassium retention and sodium depletion. There is poor response of the subject to stress and hypoglycemia.

The adrenal medulla is the inner core of the adrenal gland.

• It is signaled by a preganglionic neuron and is a modified postganglionic neuron. It stores and secretes epinephrine and norepinephrine. They are released into the blood by sympathetic stimulation.

• These two hormones vary in their affinities for different kinds of alpha and beta adrenergic receptors on target organs. Epinephrine shows exclusive beta-2 receptor activation.

• Epinephrine reinforces the sympathetic nervous system and exerts additional metabolic effects.

• Its responses are the fight or flight responses. This hormone constricts most blood vessels supplying organs, raising the total peripheral resistance. However, it dilates the blood vessels supplying the heart and skeletal muscles.

• Metabolically it promotes glycogenolysis (liver and skeletal muscles) while stimulating glucagon secretion and inhibiting insulin secretion. This hormone also promotes lipolysis. It also causes CNS arousal.

The stress response is a pattern of reactions to a situation that threatens homeostasis.

• It is a common group of responses (general adaptation syndrome) to noxious stimuli. The sympathetic nervous system and epinephrine have a role in these responses.

• Cardiac output increases. Blood is shunted to the heart and skeletal muscles while being diverted away from other organs.

• The CRH-ACTH-cortisol system is also activated in these responses. Glucose is elevated in the blood.

• Blood glucose is elevated by decreased insulin and increased glucagon secretions.

• The renin-angiotensin-aldosterone system and vasopressin activity maintain blood pressure and blood volume.

• The multifaceted stress response is coordinated by the hypothalamus. It activates the sympathetic nervous system and CRH-ACTH-cortisol release.

• Activation of this response by chronic psychosocial stressors may be harmful.

Fig. 17-23, p. 560

Stressor

Hypothalamus

Sympathetic nervous system

CRH

Anteriorpituitary

ACTH

Adrenal cortex

Cortisol

Posteriorpituitary

Vasopressin

Adrenal medulla

Epinephrine

Glucagon-secreting cellsInsulin-secreting cells

Endocrinepancreas

Glucagon Insulin

Arteriolarsmooth muscle

Vasoconstriction

Blood flowthrough kidneys

Renin Angiotensin Aldosterone

Table 17-3, p. 559

The endocrine system controls fuel metabolism.

• Metabolism is all of the chemical reactions within the cells of the body. These reactions include the degradation, synthesis, and transformation of proteins, carbohydrates, and lipids.

• Anabolism is the synthesis of larger organic molecules. Anabolic reactions require ATP. Catabolism is the breakdown of large molecules. These reactions can include hydrolysis and the oxidation of glucose to make ATP.

• Normally the rates of anabolism and catabolism are in balance in the adult.

• Nutrients from meals must be stored and released between meals. The brain needs a constant supply of glucose. It cannot store glycogen.

Table 17-4, p. 561

Fig. 17-24, p. 562

Food intake

Absorbable units

Dietary protein Dietary carbohydrate

Dietary triglyceride fat

D I G E S T I O N

Amino acids Glucose Fatty

acids Monoglycerides

A B S O R P T I O N

Metabolic poolin body

Body proteins(structural orsecretory products)

Amino acids

Urea Urinary excretion(elimination from body)

Storage, structural, andfunctional macromolecules in cells

Glycogen storagein liver and muscle

Triglyceridesin adipose tissuestores (fat)

Glucose

Fatty acids

Oxidation to CO2 + H2O + ATP (energy)

Expired(elimination from body)

Use as metabolic fuelin cells

Nutrients are stored for use between meals.

• Excess circulating glucose is stored as glycogen in the liver and skeletal muscles.

• Excess circulating fatty acids from the diet are stored into triglycerides, mainly in adipose tissue.

• Excess amino acids not needed for protein synthesis are converted to glucose and fatty acids and are ultimately stored as triglycerides in adipose tissue. Muscles are the main site of amino acid storage.

• During fasting many body cells will burn fatty acids to spare glucose for the brain. To supply the brain, amino acids can be converted to glucose by gluconeogenesis.

• Metabolic fuels are stored during the absorptive state. This occurs when ingested nutrients are being absorbed into the blood.

• Metabolic fuels are mobilized during the postabsorptive state. Nutrients are not being absorbed at this time. Stored molecules are catabolized to maintain needed blood concentrations.

Table 17-5, p. 563

Insulin and glucagon from the pancreas regulate fuel metabolism.

• They are the dominant hormonal regulators that change metabolic pathways.

• The endocrine cells in the pancreas are organized into the islets of Langerhans. The beta cells produce insulin. The alpha cells produce glucagon. Somatostatin from pancreatic D cells can inhibit both of these hormones.

• Insulin lowers blood glucose, fatty acid, and amino acid levels. It promotes their storage.

• Insulin facilitates glucose transport into most cells. A glucose transporter acts as a plasma membrane carrier to accomplish this process. Insulin and this transporter also assist the transport of fatty acids into tissues. Insulin catalyzes the conversion of fatty acids into glucose.

• Insulin stimulates glycogenesis in skeletal muscle and liver cells. This hormone inhibits glycogenolysis and gluconeogenesis.

• Insulin promotes the transport and incorporation of amino acids into cells for protein synthesis.

Fig. 17-25, p. 566

Gastrointestinalhormones

Blood glucose concentration

Blood amino acid concentration

Major control

Food intake

Parasympatheticstimulation Islet cells

Sympathetic stimulation(and epinephrine)

Insulin secretion

Blood glucoseBlood fatty acidsBlood amino acidsProtein synthesisFuel storage

Fig. 17-27, p. 572

Blood glucose

cell cell

Glucagon Insulin

Blood glucoseto normal

Blood glucose

cell cell

Glucagon Insulin

Blood glucoseto normal

Table 17-7, p. 572

An increase in blood glucose concentration increases the secretion of insulin.

• This secretion (e.g., during the absorptive state) brings blood glucose down to a normal level.

• A fall in glucose below normal inhibits insulin secretion. This shifts metabolism from the absorption to the postabsorptive pattern.

• Elevated amino acids in the blood stimulate insulin secretion. The sympathetic nervous system decreases insulin secretion.

• Inadequate insulin action produces diabetes mellitus. The result is hyperglycemia. Type I diabetes mellitus is due to an insulin deficiency. Type II is due to the reduced sensitivity of target cells to the presence of the hormone.

Low insulin activity has several consequences.

• Except for hyperglycemia the effect is similar to a prolonged postabsorptive state on carbohydrate metabolism.

• Glucosuria occurs. Excess urination also occurs. This can lead to circulatory failure, renal failure, and dehydration.

• Lipolysis is decreased. Fatty acids are mobilized from triglycerides. Liver use of fatty acids leads to ketosis. Acidosis develops and can depress brain function.

• Protein metabolism shifts to protein catabolism. This can reduce growth and lead to the wasting of skeletal muscles.

• Long-term complications of diabetes mellitus include degenerative disorders of the vascular and nervous systems.

Diabetes Mellitus

• The major features of DM are:1.Hyperglycemia (increased blood glucose levels)

is the corner stone presentation in DM.2.Polyuria – increased urine output3.Polydipsia – excessive thirst4.Polyphagia – excessive hunger and food

consumption

p. 569

Fig. 17-26, p. 570

Insulin deficiency

Hepaticglucoseoutput

Glucoseuptakeby cells

Triglyceridesynthesis Lipolysis Amino acid

uptake by cellsProteindegradation

Hyperglycemia Intracellularglucosedeficiency

Bloodfattyacids

Musclewasting

Glucosuria

Polyphagia Alternativeenergy source

Bloodamino acids

WeightlossOsmotic diuresis

Polyuria

Dehydration Polydipsia KetosisGluconeogenesis

Cellularshrinking

Blood volume

Peripheralcirculatoryfailure

Renal failureDeath

Low cerebralblood flow

Nervous systemmalfunction

Metabolicacidosis

Diabeticcoma

Increasedventilation

Aggravation of hyperglycemia

Other facts on blood glucose control include:

• Insulin excess causes brain-starving hypoglycemia. The brain cannot store glycogen and starves under this circumstance.

• Glucagon opposes the actions of insulin. It promotes glycogenolysis. This hormone also promotes fat breakdown. In addition, it promotes the breakdown of proteins in the liver.

• Glucagon secretion increases during the postabsorptive state. Its secretion increases when the blood concentration of glucose is too low.

• Therefore, insulin and glucagon work as a team to control the concentration of glucose and fatty acids in the blood.

• However, an excess of glucagon can aggravate the hyperglycemia of diabetes mellitus.

• The growth hormone, cortisol, epinephrine, and glucagon are insulin antagonists. They increase blood glucose.

The endocrine system controls calcium metabolism.

• Blood calcium must be controlled. It has numerous functions including neuromuscular excitability, excitation-coupling in cardiac and smooth muscle, stimulus-secretion coupling, maintenance of tight junctions between cells, and blood clotting.

• The parathyroid hormone (PTH) raises the level of calcium ions in the blood. It signals the bones, kidneys, and intestine. It releases stored calcium from the bones into the blood.

• This hormone also lowers phosphate ions in the blood.• Bone remodeling results from an interplay of bone deposition

(osteoblast activity) and bone resorption (osteoclast activity). Usually the rates of these two processes are about equal in the adult.

Parathyroid Glands

• Tiny glands embedded in the posterior aspect of the thyroid

• Cells are arranged in cords containing oxyphil and chief cells

• Chief (principal) cells secrete PTH• PTH (parathormone) regulates calcium balance in

the blood

Parathyroid Glands

The overall effect of PTH is to release calcium ions from bones and release it into the blood.

• Bone deposition of calcium increases the mechanical strength of bones. Too much bone resorption can weaken bones. Osteoporosis is a reduction in bone mass.

• PTH quickly releases calcium from the labile pool in bones. It stimulates the transfer of calcium across the osteocytic-osteoblastic bone membranes in bones.

• Calcium is quickly replaced in this area from mineralized bone.• PTH also promotes the slow transfer of calcium and phosphate

from the stable pool in bones.• This hormone promotes the localized dissolution of calcium in

bones into the surrounding ECF. This helps to maintain calcium in the plasma.

PTH has other target organs in addition to the bones.

• PTH also signals the kidneys to conserve calcium and to eliminate phosphate ions. This effect adds calcium to the blood plasma.

• There is an inverse relationship between calcium and phosphate levels in the blood plasma. The product of their two concentrations must be constant.

• PTH also promotes the absorption of calcium and phosphate ions by the intestine. Vitamin D increases calcium absorption in the intestine.

• PTH secretion rises in response to a decrease in calcium in the blood.

• Calcitonin from the thyroid gland lowers the calcium level in the blood. However, its role is not important in calcium metabolism. It does protect against hypercalcemia.

Calcium disorders can arise. • Hypercalcemia can occur by excess PTH secretion. This reduces the excitability of

muscle and nervous tissue.• Cardiac disturbances can occur.• Other effects are the thinning of bones and the development of kidney stones.• PTH hyposecretion leads to hypocalcemia and hyperphosphatemia. This increases

neuromuscular excitability. • A deficiency of vitamin D decreases intestinal absorption of calcium. This can lead to

rickets in children and osteomalacia in adults.

A peptide hormone produced by the parafollicular, or C, cellsd located in the thyroid glan:

• Lowers blood calcium rapidly within minutes• Antagonist to parathyroid hormone (PTH)

Calcitonin

Fig. 17-29, p. 575

Plasma Ca2+ Plasma Ca2+

Parathyroid glands Thyroid C cells

PTH Calcitonin

Plasma Ca2+ Plasma Ca2+

Fig. 17-30, p. 577

Relieves Plasma Ca2+

Parathyroid glands

PTH

BoneKidneys

Renal tubularCa2+ reabsorption

Activationof vitamin D

Mobilization of Ca2+ from bone

Intestine

Urinary excretionof Ca2+

Absorption of Ca2+ in intestine

Plasma Ca2+

1,25 dihydroxyvitamin D3• Synthesis:

• Pre-vitamin D3 is synthesized in the skin.• Pre-vitamin D3 isomerized to vitamin D3 (cholecalciferol).• Cholecalciferol is hydroxylated in liver to form 25

hydroxycholecalciferol. • In proximal convoluted tubule is hydroxylated to 1,25

dihydroxycholecalciferol (active vitamin D3).• Functions:

• Directly stimulates intestinal absorption of Ca2+ and P043-.

• When Ca2+ intake is inadequate, directly stimulates bone reabsorption.

• Stimulates reabsorption of Ca2+ and P043- by the kidney.

• Simultaneously raising Ca2+ and P043- results in increased

tendency of these 2 ions to precipitate as hydroxyapatite crystals.

• Stimulated by PTH.