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Principles of Human Anatomy and Physiology, 11e

Chapter 18

The Endocrine System Lecture Outline

Chapter 18 The Endocrine System

• The nervous and endocrine systems act as a coordinated interlocking supersystem, the

neuroendocrine system

• The endocrine system controls body activities by releasing mediator molecules called

hormones

– hormones released into the bloodstream travel throughout the body – results may take hours, but last longer • The nervous system controls body actions through

nerve impulses

– certain parts release hormones into blood – rest releases neurotransmitters excite or inhibit nerve, muscle & gland cells – results in milliseconds, brief duration of effects

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NERVOUS and ENDOCRINE SYSTEM

• The nervous system causes muscles to contract or glands to secrete. The endocrine system affects virtually all body tissues by altering metabolism, regulating growth and development, and influencing reproductive processes.

• Parts of the nervous system stimulate or inhibit the release of hormones.

• Hormones may promote or inhibit the generation of nerve impulses.

• Table 18.1 compares the characteristics of the nervous and endocrine systems.

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General Functions of Hormones

• Help regulate: – extracellular fluid – metabolism – biological clock – contraction of cardiac & smooth muscle – glandular secretion – some immune functions • Growth & development • Reproduction • Hormones have powerful effects when present in very low concentrations.

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Endocrine Glands Defined

• Exocrine glands – secrete products into ducts which empty into body cavities or body surface – sweat, oil, mucous, & digestive glands • Endocrine glands – secrete products (hormones) into bloodstream – pituitary, thyroid, parathyroid, adrenal, pineal – other organs secrete hormones as a 2nd function – hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach, liver, small intestine, skin, heart & placenta

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Hormone Receptors

• Hormones only affect target cells with specific membrane proteins called receptors

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Hormone Receptors

• Although hormones travel in blood throughout the body, they affect only specific

target cells

– Target cells have specific protein or glycoprotein receptors to which hormones bind.

• Receptors are constantly being synthesized and broken down.

• Synthetic hormones that block the receptors for particular naturally occurring hormones are available as drugs. (Clinical Application)

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Regulation of Hormone Receptors

• Receptors are constantly being synthesized & broken down – range of 2000-100,000 receptors / target cell • Down-regulation – excess hormone leads to a decrease in number of receptors • receptors undergo endocytosis and are degraded – decreases sensitivity of target cell to hormone • Up-regulation – deficiency of hormone leads to an increase in the number of receptors – target tissue becomes more sensitive to the hormone

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Blocking Hormone Receptors

• Synthetic drugs may block receptors for naturally occurring hormones – Normally, progesterone levels drop once/month leading to menstruation. Progesterone levels are maintained when a woman becomes pregnant.

– RU486 (mifepristone) binds to the receptors for progesterone preventing progesterone from sustaining the endometrium in a pregnant woman • brings on menstrual cycle • used to induce abortion

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Circulating and Local Hormones

• Hormones that travel in blood and act on distant target cells are called

circulating hormones

endocrines

• Hormones that act locally without first entering the blood stream are called

local hormones

– Those that act on neighboring cells are called

paracrines

– Those that act on the same cell that secreted them are termed

autocrines

• Figure 18.2 compares the site of action of circulating and local hormones.

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Circulating & Local Hormones

• Circulating hormones • Local hormones – paracrines – autocrines

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Chemical Classes of Hormones - Overview

• • • Table 18.2 provides a summary of the hormones.

Lipid-soluble hormones

include the steroids, thyroid hormones, and nitric oxide, which acts as a local hormone in several tissues.

Water-soluble hormones

include the amines; peptides, proteins, and glycoproteins; and eicosanoids.

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Principles of Human Anatomy and Physiology, 11e

Lipid-soluble Hormones

• Steroids – lipids derived from cholesterol on SER – different functional groups attached to core of structure provide uniqueness • Thyroid hormones – tyrosine ring plus attached iodines are lipid-soluble • Nitric oxide is gas

Principles of Human Anatomy and Physiology, 11e

Water-soluble Hormones

• Amine, peptide and protein hormones – modified amino acids or amino acids put together – serotonin, melatonin, histamine, epinephrine – some glycoproteins • Eicosanoids – derived from arachidonic acid (fatty acid) – prostaglandins or leukotrienes

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General Mechanisms of Hormone Action • Hormone binds to cell surface or receptor inside target cell • Cell may then – synthesize new molecules – change permeability of membrane – alter rates of reactions • Each target cell responds to hormone differently At liver cells---insulin stimulates glycogen synthesis At adipocytes---insulin stimulates triglyceride synthesis

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Action of Lipid-Soluble Hormone

•

Lipid-soluble hormones

cells.

bind to and activate receptors within – The activated receptors then alter gene expression which results in the formation of new proteins.

– The new proteins alter the cells activity and result in the physiological responses of those hormones.

• Figure 18.3 shows this mechanism of action.

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Action of Lipid-Soluble Hormones

• Hormone diffuses through phospholipid bilayer & into cell • Binds to receptor turning on/off specific genes • New mRNA is formed & directs synthesis of new proteins • New protein alters cell’s activity

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Action of Water-Soluble Hormones

•

Water-soluble hormones

alter cell functions by activating plasma membrane receptors, which set off a cascade of events inside the cell.

– The water-soluble hormone that binds to the cell membrane receptor is the

first messenger

– A

second messenger

is released inside the cell where hormone stimulated response takes place.

• A typical mechanism of action of a water-soluble hormone using cyclic AMP as the second messenger is seen in Figure 18.4.

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Action of Water-Soluble Hormones

• The hormone binds to the membrane receptor.

• The activated receptor activates a membrane

G-protein

which turns on

adenylate cyclase

• • Adenylate cyclase converts ATP into cyclic AMP which activates protein kinases.

Protein kinases

phosphorylate enzymes which catalyze reactions that produce the physiological response.

• Since hormones that bond to plasma membrane receptors initiate a cascade of events, they can induce their effects at very low concentrations.

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Action of Water-Soluble Hormones

• Can not diffuse through plasma membrane • Hormone receptors are integral membrane proteins – act as first messenger • The hormone binds to the membrane receptor.

• The activated receptor activates a membrane

G-protein

which turns on

adenylate cyclase

• • Adenylate cyclase converts ATP into cyclic AMP which activates protein kinases.

Protein kinases

enzymes which catalyze reactions that produce the physiological response.

phosphorylate

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Principles of Human Anatomy and Physiology, 11e

Water-soluble Hormones

• Cyclic AMP is the 2nd messenger – kinases in the cytosol speed up/slow down physiological responses • Phosphodiesterase inactivates cAMP quickly • Cell response is turned off unless new hormone molecules arrive

Second Messengers

• Some hormones exert their influence by increasing the synthesis of cAMP – ADH, TSH, ACTH, glucagon and epinephrine • Some exert their influence by decreasing the level of cAMP – growth hormone inhibiting hormone • Other substances can act as 2nd messengers – calcium ions – cGMP • A hormone may use different 2nd messengers in different target cells

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Amplification of Hormone Effects

• Single molecule of hormone binds to receptor • Activates 100 G-proteins • Each activates an adenylate cyclase molecule which then produces 1000 cAMP • Each cAMP activates a protein kinase, which may act upon 1000’s of substrate molecules • One molecule of epinephrine may result in breakdown of millions of glycogen molecules into glucose molecules

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Cholera Toxin and G Proteins

• Toxin is deadly because it produces massive watery diarrhea and person dies from dehydration • Toxin of cholera bacteria causes G-protein to lock in activated state in intestinal epithelium • Cyclic AMP causes intestinal cells to actively transport chloride (Na+ and water follow) into the lumen • Person die unless ions and fluids are replaced & receive antibiotic treatment

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Hormonal Interactions

• The responsiveness of a target cell to a hormone depends on the hormone’s concentration, the abundance of the target cell’s hormone receptors, and influences exerted by other hormones.

• Three hormonal interactions are the –

permissive effect

– –

synergistic effect antagonist effect Principles of Human Anatomy and Physiology, 11e 26

Hormonal Interactions

• Permissive effect – a second hormone, strengthens the effects of the first – thyroid strengthens epinephrine’s effect upon lipolysis • Synergistic effect – two hormones acting together for greater effect – estrogen & LH are both needed for oocyte production • Antagonistic effects – two hormones with opposite effects – insulin promotes glycogen formation & glucagon stimulates glycogen breakdown

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Control of Hormone Secretion

• Regulated by signals from nervous system, chemical changes in the blood or by other hormones • Negative feedback control (most common) – decrease/increase in blood level is reversed • Positive feedback control – the change produced by the hormone causes more hormone to be released • Disorders involve either hyposecretion or hypersecretion of a hormone

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HYPOTHALAMUS AND PITUITARY GLAND

• The

hypothalamus

is the major integrating link between the nervous and endocrine systems.

– Hypothalamus receives input from cortex, thalamus, limbic system & internal organs – Hypothalamus controls pituitary gland with 9 different releasing & inhibiting hormones • The hypothalamus and the pituitary gland (hypophysis) regulate virtually all aspects of growth, development, metabolism, and homeostasis.

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Anatomy of Pituitary Gland

• The pituitary gland is located in the sella turcica of the sphenoid bone and is differentiated into the

anterior pituitary

(

adenohypophysis

), the

posterior pituitary

(

neurohypophysis

), and

pars intermedia

(avascular zone in between (Figures 18.5 and 18.21b).

• Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid – Infundibulum attaches it to brain • Anterior lobe = 75% – develops from roof of mouth • Posterior lobe = 25% – ends of axons of 10,000 neurons found in hypothalamus – neuroglial cells called pituicytes

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Anterior Pituitary Gland (Adenohypophysis)

• The blood supply to the anterior pituitary is from the

superior hypophyseal arteries

• Hormones of the anterior pituitary and the cells that produce the: – Human growth hormone (hGH) is secreted by somatotrophs.

– Thyroid-stimulating hormone (TSH) is secreted by thyrotrophs.

– Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotrophs.

– Prolactin (PRL) is secreted by lactrotrophs.

– Adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH) are secreted by corticotrophs.

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• Controlling hormones enter blood • Travel through portal veins • Enter anterior pituitary at capillaries

Principles of Human Anatomy and Physiology, 11e

Flow of Blood to Anterior Pituitary

Principles of Human Anatomy and Physiology, 11e

Anterior Pituitary

Feedback

• Secretion of anterior pituitary gland hormones is regulated by

hypothalamic regulating hormones

and by

negative feedback

mechanisms (Figure 18.6, Table 18.3).

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Principles of Human Anatomy and Physiology, 11e

Negative Feedback Systems • Decrease in blood levels • Receptors in hypothalamus & thyroid • Cells activated to secrete more TSH or more T3 & T4 • Blood levels increase

Positive Feedback

• Oxytocin stimulates uterine contractions • Uterine contractions stimulate oxytocin release

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Human Growth Hormone and Insulin-like Growth Factors

•

Human growth hormone

pituitary hormone.

(

hGH

) is the most plentiful anterior • It acts indirectly on tissues by promoting the synthesis and secretion of small protein hormones called

insulin-like growth factors

(

IGFs

– IGFs stimulate general body growth and regulate various aspects of metabolism.

– Various stimuli promote and inhibit hGH production (Figure 18.7).

– One symptom of excess hGH is hyperglycemia. (Clinical Application)

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Human Growth Hormone

• Produced by somatotrophs • target cells synthesize insulinlike growth – common target cells are liver, skeletal muscle, cartilage and bone – increases cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins – stimulate lipolysis in adipose so fatty acids used for ATP – retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain

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Principles of Human Anatomy and Physiology, 11e

Regulation of hGH

• Low blood sugar stimulates release of GHRH from hypothalamus – anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells • High blood sugar stimulates release of GHIH from hypothalamus – less hGH from anterior pituitary, glycogen does not breakdown into glucose

Diabetogenic Effect of Human Growth Hormone

• Excess of growth hormone – raises blood glucose concentration – pancreas releases insulin continually – beta-cell burnout • Diabetogenic effect – causes diabetes mellitis if no insulin activity can occur eventually

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Thyroid Stimulating Hormone (TSH)

• Hypothalamus regulates thyrotroph cells • Thyrotroph cells produce TSH • TSH stimulates the synthesis & secretion of T3 and T4 • Metabolic rate stimulated

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Follicle Stimulating Hormone (FSH)

• Releasing hormone from hypothalamus controls gonadotrophs • Gonadotrophs release follicle stimulating hormone • FSH functions – initiates the formation of follicles within the ovary – stimulates follicle cells to secrete estrogen – stimulates sperm production in testes

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Luteinizing Hormone (LH)

• Releasing hormones from hypothalamus stimulate gonadotrophs • Gonadotrophs produce LH • In females, LH stimulates – secretion of estrogen – ovulation of 2nd oocyte from ovary – formation of corpus luteum – secretion of progesterone • In males, LH stimulates the interstitial cells of the testes to secrete testosterone.

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Prolactin (PRL)

•

Prolactin

(

PRL

), together with other hormones, initiates and maintains milk secretion by the mammary glands.

– Hypothalamus regulates lactotroph cells – Lactotrophs produce prolactin – Under right conditions, prolactin causes milk production • Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production

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Adrenocorticotrophic Hormone

•

Adrenocorticotrophic hormone

(

ACTH

) controls the production and secretion of hormones called glucocorticoids by the cortex of the adrenal gland. – Hypothalamus releasing hormones stimulate corticotrophs – Corticotrophs secrete ACTH & MSH – ACTH stimulates cells of the adrenal cortex that produce glucocorticoids

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Melanocyte-Stimulating Hormone

•

Melanocyte-stimulating hormone

(

MSH

) increases skin pigmentation although its exact role in humans is unknown.

– Releasing hormone from hypothalamus increases MSH release from the anterior pituitary – Secreted by corticotroph cells • Function not certain in humans (increase skin pigmentation in frogs )

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Posterior Pituitary Gland (Neurohypophysis)

• Although the posterior pituitary gland does not synthesize hormones, it does store and release two hormones.

– Hormones made by the hypothalamus and stored in the posterior pituitary are

oxytocin

(

) and

antidiuretic hormone

(

ADH

– The neural connection between the hypothalamus and the neurohypophysis is via the

hypothalamohypophyseal tract

(Figure 18.8).

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Posterior Pituitary Gland (Neurohypophysis) • Does not synthesize hormones • Consists of axon terminals of hypothalamic neurons • Neurons release two neurotransmitters into capillaries – antidiuretic hormone – oxytocin

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Oxytocin

• Two target tissues both involved in neuroendocrine reflexes • During delivery – baby’s head stretches cervix – hormone release enhances uterine – muscle contraction – baby & placenta are delivered • After delivery

Oxytocin

stimulates contraction of the uterus and ejection (let-down) of milk from the breasts. • Nursing a baby after delivery stimulates oxytocin release, promoting uterine contractions and the expulsion of the placenta (Clinical Application).

• suckling & hearing baby’s cry stimulates milk ejection

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Principles of Human Anatomy and Physiology, 11e

Oxytocin during Labor

• Stimulation of uterus by baby • Hormone release from posterior pituitary • Uterine smooth muscle contracts until birth of baby • Baby pushed into cervix, increase hormone release • More muscle contraction occurs • When baby is born, positive feedback ceases

ADH

•

Antidiuretic hormone

stimulates water reabsorption by the kidneys and arteriolar constriction.

• The effect of ADH is to decrease urine volume and conserve body water.

• ADH is controlled primarily by osmotic pressure of the blood (Figure 18.9).

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Antidiuretic Hormone (ADH)

• Known as vasopressin • Functions – decrease urine production – decrease sweating – increase BP

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Principles of Human Anatomy and Physiology, 11e

Regulation of ADH

• Dehydration – ADH released • Overhydration – ADH inhibited

THYROID GLAND - Overview

• The

thyroid gland

is located just below the larynx and has right and left lateral lobes (Figure 18.10a).

• Histologically, the thyroid consists of the thyroid follicles composed of

follicular cells

, which secrete the thyroid hormones

thyroxine

(

T 4

) and

triiodothyronine

(

T 3

), and

parafollicular cells

, which secrete calcitonin (

) (Figures 18.10b and 18.13c).

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Thyroid Gland

• On each side of trachea is lobe of thyroid • Weighs 1 oz & has rich blood supply

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Histology of Thyroid Gland

• Follicle = sac of stored hormone (colloid) surrounded by follicle cells that produced it – T3 & T4 • Inactive cells are short • In between cells called parafollicular cells – produce calcitonin

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Photomicrograph of Thyroid Gland

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Formation, Storage, and Release of Thyroid Hormones

• Thyroid hormones are synthesized from iodine and tyrosine within a large glycoprotein molecule called

thyroglobulin

(

TGB

) and are transported in the blood by plasma proteins, mostly thyroxine-binding globulin (TBG).

• The formation, storage, and release steps include – iodide trapping, – synthesis of thyroglobulin, – oxidation of iodide, – iodination of tyrosine, – coupling of T 1 and T 2 , – pinocytosis and digestion of colloid, – secretion of thyroid hormones, and transport in blood (Figure 18.11).

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Principles of Human Anatomy and Physiology, 11e

Formation of Thyroid Hormone

• Iodide trapping by follicular cells • Synthesis of thyroglobulin (TGB) • Release of TGB into colloid • Iodination of tyrosine in colloid • Formation of T3 & T4 by combining T1 and T2 together • Uptake & digestion of TGB by follicle cells • Secretion of T3 & T4 into blood

Principles of Human Anatomy and Physiology, 11e

Actions of Hormones from Thyroid Gland

• T3 & T4 – thyroid hormones responsible for our metabolic rate, synthesis of protein, breakdown of fats, use of glucose for ATP production • Calcitonin – responsible for building of bone & stops reabsorption of bone (lowers blood levels of Calcium)

Principles of Human Anatomy and Physiology, 11e

Control of T3 & T4 Secretion

• Negative feedback system • Low blood levels of hormones stimulate hypothalamus • It stimulates pituitary to release TSH • TSH stimulates gland to raise blood levels

PARATHYROID GLANDS

• • The

parathyroid glands

are embedded on the posterior surfaces of the lateral lobes of the thyroid – –

principal cells

produce

oxyphil cells … parathyroid hormone

function is unknown (Figure 18.13).

Parathyroid hormone

(

PTH

) regulates the homeostasis of calcium and phosphate • increase blood calcium level • decrease blood phosphate level – increases the number and activity of osteoclasts – increases the rate of Ca +2 and Mg +2 from reabsorption from urine and inhibits the reabsorption of HPO 4 -2 more is secreted in the urine so – promotes formation of calcitriol, which increases the absorption of Ca +2 , Mg +2 ,and HPO 4 -2 from the GI tract

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Parathyroid Glands

• 4 pea-sized glands found on back of thyroid gland

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Histology of Parathyroid Gland

• Principal cells produce parathyroid hormone (PTH) • Oxyphil cell function is unknown

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Blood Calcium

• Blood calcium level directly controls the secretion of calcitonin and parathyroid hormone via negative feedback loops that do not involve the pituitary gland (Figure 18.14).

• Table 18.7 summarizes the principal actions and control of secretion of parathyroid hormone.

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Regulation of Calcium Blood Levels

• High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CT

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Adrenal Glands

• The

adrenal glands

are located superior to the kidneys (Figure 18.15) • 3 x 3 x 1 cm in size and weighs 5 grams • consists of an outer cortex and an inner medulla.

– Cortex produces 3 different types of hormones from 3 zones of cortex – Medulla produces epinephrine & norepinephrine

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Adrenal Cortex

• The adrenal cortex is divided into three zones, each of which secretes different hormones (Figure 18.15).

– The zona glomerulosa (outer zone) • secretes mineralocorticoids.

– The zona fasciculata (middle zone) • secretes glucocorticoids.

– The

zona reticularis

(inner zone) • secretes

androgens

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Principles of Human Anatomy and Physiology, 11e

Histology of Adrenal Gland

• Cortex – 3 zones • Medulla

Structure of Adrenal Gland

Principles of Human Anatomy and Physiology, 11e

• Cortex derived from mesoderm • Medulla derived from ectoderm

Mineralocorticoids

• 95% of hormonal activity due to aldosterone • Functions – increase reabsorption of Na+ with Cl- , bicarbonate and water following it – promotes excretion of K+ and H+ • Hypersecretion = tumor producing aldosteronism – high blood pressure caused by retention of Na+ and water in blood

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Regulation of Aldosterone

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Glucocorticoids

• 95% of hormonal activity is due to cortisol • Functions = help regulate metabolism – increase rate of protein catabolism & lipolysis – conversion of amino acids to glucose – stimulate lipolysis – provide resistance to stress by making nutrients available for ATP production – raise BP by vasoconstriction – anti-inflammatory effects reduced (skin cream) • reduce release of histamine from mast cells • decrease capillary permeability • depress phagocytosis

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Principles of Human Anatomy and Physiology, 11e

Regulation of Glucocorticoids

• Negative feedback

Androgens from Zona Reticularis

• Small amount of male hormone produced – insignificant in males – may contribute to sex drive in females – is converted to estrogen in postmenopausal females

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Adrenal Medulla

• Chromaffin cells receive direct innervation from sympathetic nervous system – develop from same tissue as postganglionic neurons • Produce epinephrine & norepinephrine • Hormones are sympathomimetic – effects mimic those of sympathetic NS – cause fight-flight behavior • Acetylcholine increase hormone secretion by adrenal medulla

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PANCREATIC ISLETS

• The

pancreas

is a flattened organ located posterior and slightly inferior to the stomach and can be classified as both an endocrine and an exocrine gland (Figure 18.18). • Histologically, it consists of

pancreatic islets

islets of Langerhans

(Figure 18.19) and clusters of cells (acini) (enzyme-producing exocrine cells).

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Anatomy of Pancreas • Organ (5 inches) consists of head, body & tail • Cells (99%) in acini produce digestive enzymes • Endocrine cells in pancreatic islets produce hormones

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Cell Organization in Pancreas

• Exocrine acinar cells surround a small duct • Endocrine cells secrete near a capillary

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Histology of the Pancreas

• 1 to 2 million pancreatic islets • Contains 4 types of endocrine cells

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Cell Types in the Pancreatic Islets

• Alpha cells (20%) produce glucagon • Beta cells (70%) produce insulin • Delta cells (5%) produce somatostatin • F cells produce pancreatic polypeptide

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Principles of Human Anatomy and Physiology, 11e

Regulation

• Regulation of glucagon and insulin secretion is via negative feedback mechanisms (Figure 18.19).

– Low blood glucose stimulates release of glucagon – High blood glucose stimulates secretion of insulin • Table 18.9 summarizes the hormones produced by the pancreas, their principal actions, and control of secretion.

Ovaries and Testes

• Ovaries – estrogen, progesterone, relaxin & inhibin – regulate reproductive cycle, maintain pregnancy & prepare mammary glands for lactation • Testes – produce testosterone – regulate sperm production & 2nd sexual characteristics • Table 18.10 summarizes the hormones produced by the ovaries and testes and their principal actions.

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Pineal Gland

• Small gland attached to 3rd ventricle of brain • Consists of pinealocytes & neuroglia • Melatonin responsible for setting of biological clock • Jet lag & SAD treatment is bright light

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Effect of Light on Pineal Gland

• Melatonin secretion producing sleepiness occurs during darkness due to lack of stimulation from sympathetic ganglion

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Seasonal Affective Disorder and Jet Lag • Depression that occurs during winter months when day length is short • Due to overproduction of melatonin • Therapy – exposure to several hours per day of artificial light as bright as sunlight – speeds recovery from jet lag

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Thymus Gland

• Important role in maturation of T cells • Hormones produced by gland promote the proliferation & maturation of T cells – thymosin – thymic humoral factor – thymic factor – thymopoietin

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OTHER HORMONES and GROWTH FACTORS

• Several body tissues other than those usually classified as endocrine glands also contain endocrine tissue and thus secrete hormones.

• Table 18.11 summarizes these hormones and their actions.

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Eicosanoids

• Local hormones released by all body cells • alter the production of second messengers, such as cyclic AMP – Leukotrienes influence WBCs & inflammation – Prostaglandins alter: • smooth muscle contraction, glandular secretion, blood flow, platelet function, nerve transmission, metabolism.

• Aspirin and related nonsteroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen and acetaminophen, inhibit a key enzyme in prostaglandin synthesis and are used to treat a wide variety of inflammatory disorders.

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Nonsteroidal Anti-inflammatory Drugs

• Answer to how aspirin or ibuprofen works was discovered in 1971 – inhibit a key enzyme in prostaglandin synthesis without affecting the synthesis of leukotrienes • Treat a variety of inflammatory disorders – rheumatoid arthritis • Usefulness of aspirin to treat fever & pain implies prostaglandins are responsible for those symptoms

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Growth Factors

• Substances with mitogenic qualities – cause cell growth from cell division • Many act locally as autocrines or paracrines • Selected list of growth factors (Table 18.12) – epidermal growth factor (EGF), – platelet-derived growth factor (PDGF), – fibroblast growth factor (FGF), – nerve growth factor (NGF), – tumor angiogenesis factors (TAFs), – Insulin-like growth factor (IFG), – cytokines

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STRESS RESPONSE

• The stimuli that produce the general adaptation syndrome are called

stressors

• Stressors include almost any disturbance: heat or cold, surgical operations, poisons, infections, fever, and strong emotional responses.

• Stages of the General Adaptation Syndrome

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Stress & General Adaptation Syndrome

• Stress response is set of bodily changes called general adaptation syndrome (GAS) • Any stimulus that produces a stress response is called a stressor • Stress resets the body to meet an emergency – eustress is productive stress & helps us prepare for certain challenges – distress type levels of stress are harmful • lower our resistance to infection

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Principles of Human Anatomy and Physiology, 11e

General Adaptation Syndrome

Alarm Reaction (Fight-or-Flight)

• The

alarm reaction

is initiated by nerve impulses from the hypothalamus to the sympathetic division of the autonomic nervous system and adrenal medulla (Figure 18.20a).

• Dog attack – increases circulation – promote catabolism for energy production – promotes ATP synthesis – nonessential body functions are inhibited • digestive, urinary & reproductive

Principles of Human Anatomy and Physiology, 11e 95

Resistance Reaction

• Initiated by hypothalamic releasing hormones (long-term reaction to stress) – corticotropin, growth hormone & thyrotropin releasing hormones • Results – increased secretion of aldosterone acts to conserve Na+ (increases blood pressure) and eliminate H+ – increased secretion of cortisol so protein catabolism is increased & other sources of glucose are found – increase thyroid hormone to increase metabolism • Allow body to continue to fight a stressor • Glucocorticoids are produced in high concentrations during stress. They create many distinct physiological effects.

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Exhaustion

• Exhaustion is caused mainly by loss of potassium, depletion of adrenal glucocorticoids, and weakened organs. If stress is too great, it may lead to death.

– Resources of the body have become depleted – Resistance stage can not be maintained – Prolonged exposure to resistance reaction hormones • wasting of muscle • suppression of immune system • ulceration of the GI tract • failure of the pancreatic beta cells

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system

Stress and Disease

• Stress can lead to disease by inhibiting the immune – gastritis, ulcerative colitis, irritable bowel syndrome, peptic ulcers, hypertension, asthma, rheumatoid arthritis, migraine headaches, anxiety, and depression.

• people under stress are at a greater risk of developing chronic disease or of dying prematurely • Interleukin - 1 – link between stress and immunity – secreted by macrophages; stimulates secretion of ACTH – stimulates production of immune substances – feedback control since immune substance suppress the formation of interleukin-1

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DEVELOPMENTAL ANATOMY OF THE ENDOCRINE SYSTEM

• The pituitary gland originates from two different regions of the ectoderm.

• The anterior pituitary derives from the

neurohypophyseal bud

, located on the floor of the hypothalamus (Figure 18.21).

• The anterior pituitary is derived from an outgrowth of ectoderm from the mouth called the

hypophyseal

(

Rathke’s

)

pouch.

• The thyroid gland develops as a midventral outgrowth of endoderm, called the thyroid diverticulum, from the floor of the pharynx at the level of the second pair of pharyngeal pouches.

• Parathyroid glands develop from endoderm as outgrowths from the third and fourth pharyngeal pouches.

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Development of the Endocrine System

• Thyroid develops ---floor of pharynx 2nd pouch • Parathyroid & thymus --3 & 4 pharyngeal pouches • Pancreas from foregut

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Development of Pituitary Gland

• Events occurring between 5 and 16 weeks of age

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DEVELOPMENTAL ANATOMY OF THE ENDOCRINE SYSTEM

• The adrenal cortex is derived from intermediate mesoderm from the same region that produces the gonads. The adrenal medulla is ectodermal in origin and derives from the neural crest, which also gives rise to sympathetic ganglion and other nervous system structures (Figure 14.125b).

• The pancreas develops from the outgrowth of endoderm from the part of the foregut that later becomes the duodenum (Figure 29.12c).

• The pineal gland arises as an outgrowth between the thalamus and colliculi from ectoderm associated with the diencephalon (Figure 14.26).

• The thymus gland arises from endoderm of the third pharyngeal pouch.

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Aging and the Endocrine System

• Production of human growth hormone decreases – muscle atrophy • Production of TSH increase with age to try and stimulate thyroid – decrease in metabolic rate, increase in body fat & hypothyroidism • Thymus after puberty is replaced with adipose • Adrenal glands produce less cortisol & aldosterone • Receptor sensitivity to glucose declines • Ovaries no longer respond to gonadotropins – decreased output of estrogen (osteoporosis & atherosclerosis)

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DISORDERS: HOMEOSTATIC IMBALANCES

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Diabetes Insipidus

• dysfunction of the posterior pituitary • Hyposecretion of ADH – excretion of large amounts of dilute urine and subsequent dehydration and thirst

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Pituitary Gland Disorders

• Hyposecretion during childhood = pituitary dwarfism (proportional, childlike body) • Hypersecretion during childhood = giantism – very tall, normal proportions • Hypersecretion as adult = acromegaly – growth of hands, feet, facial features & thickening of skin

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Thyroid Gland Disorders

• Hyposecretion during infancy results in dwarfism & retardation called cretinism • Hypothyroidism in adult produces sensitivity to cold, low body temp. weight gain & mental dullness • Hyperthyroidism (Grave’s disease) – weight loss, nervousness, tremor & exophthalmos (edema behind eyes) • Goiter = enlarged thyroid (dietary)

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Parathyroid Gland Disorders

• Hypoparathyroidism results in muscle tetany.

• Hyperparathyroidism produces osteitis fibrosa cystica

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Adrenal Gland Disorders - Tumor

– Pheochromocytomas, benign tumors of the adrenal medulla, cause hypersecretion of medullary hormones and a prolonged fight-or-flight response.

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Adrenal Gland Disorders Cushing’s Syndrome

• Hypersecretion of glucocorticoids • Redistribution of fat, spindly arms & legs due to muscle loss • Wound healing is poor, bruise easily

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Adrenal Gland Disorders Addison’s disease

• Hypersecretion of glucocorticoids – hypoglycemia, muscle weakness, low BP, dehydration due to decreased Na+ in blood – mimics skin darkening effects of MSH – potential cardiac arrest

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Pancreatic Disorders

• Diabetes Mellitus – This is a group of disorders caused by an inability to produce or use insulin.

• Type I diabetes or insulin-dependent diabetes mellitus is caused by an absolute deficiency of insulin.

• Type II diabetes or insulin-independent diabetes is caused by a down-regulation of insulin receptors.

– excessive urine production (polyuria) – excessive thirst (polydipsia) – excessive eating (polyphagia) • Hyperinsulinism results when

too much

insulin is present – causes hypoglycemia and possibly insulin shock

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end

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Photographs for Review

• Figure 18.22 shows photographs of individuals suffering from various endocrine disorders.

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Adrenal Cortex - Review

• Mineralocorticoids –

Mineralocorticoids

(e.g., aldosterone) increase sodium and water reabsorption and decrease potassium reabsorption, helping to regulate sodium and potassium levels in the body.

– Secretion is controlled by the renin-angiotensin pathway (Figure 18.16) and the blood level of potassium.

• Glucocorticoids –

Glucocorticoids

(e.g., cortisol) promote breakdown of proteins, formation of glucose, lipolysis, resistance to stress, anti-inflammatory effects, and depression of the immune response.

– Secretion is controlled by CRH (corticotropin releasing hormone) and ACTH (adrenocorticotropic hormone) from the anterior pituitary (Figure 18.17).

•

Androgens

–

Androgens

secreted by the adrenal cortex usually have minimal effects.

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Adrenal Medulla - Review

• The

adrenal medulla

consists of hormone-producing cells, called chromaffin cells, which surround large blood-filled sinuses.

• Medullary secretions are

epinephrine

and

norepinephrine

(NE), which produce effects similar to sympathetic responses.

• They are released under stress by direct innervation from the autonomic nervous system. Like the glucocorticoids of the adrenal cortex, these hormones help the body resist stress. However, unlike the cortical hormones, the medullary hormones are not essential for life.

• Table 18.8 summarizes the hormones produced by the adrenal glands, the principal actions, and control of secretion.

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Review: Cell Types in the Pancreatic Islets

• • • •

Alpha cells

secrete the hormone blood glucose levels.

glucagon

which increases

Beta cells

secrete the hormone

insulin

blood glucose levels.

which decreases

Delta cells

secrete

growth hormone inhibiting hormone somatostatin

, which acts as a paracrine to inhibit the secretion of insulin and glucagon.

F-cells

secrete

pancreatic polypeptide

, which regulates release of pancreatic digestive enzymes.

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OVARIES AND TESTES - Review

• •

Ovaries

are located in the pelvic cavity and produce sex hormones (

estrogens

and

progesterone

) related to development and maintenance of female sexual characteristics, reproductive cycle, pregnancy, lactation, and normal reproductive functions. The ovaries also produce

inhibin

and

relaxin.

Testes

lie inside the scrotum and produce sex hormones (primarily

testosterone

) related to the development and maintenance of male sexual characteristics and normal reproductive functions. The testes also produce

inhibin

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PINEAL GLAND - Review

• • The

pineal gland

(

epiphysis cerebri

) is attached to the roof of the third ventricle, inside the brain (Figure 18.1).

• Histologically, it consists of secretory parenchymal cells called

pinealocytes

, neuroglia cells, and scattered postganglionic sympathetic fibers. The pineal secrets

melatonin

in a diurnal rhythm linked to the dark-light cycle.

Seasonal affective disorder

(

SAD

), a type of depression that arises during the winter months when day length is short, is thought to be due, in part, to over-production of melatonin. Bright light therapy, repeated doses of several hours exposure to artificial light as bright as sunlight, may provide relief for this disorder and for jet lag.

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THYMUS GLAND

• • The

thymus gland

immunity .

secretes several hormones related to

Thymosin, thymic humoral-factor, thymic factor thymopoietin

, and promote the proliferation and maturation of T cells, a type of white blood cell involved in immunity.

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