Chapter 18

The Endocrine System

Endocrine system

• Endo = inside• crine = secrete• hormon = to excite

– to get ~ 1# of endocrine tissue you would need to collect ALL the endocrine tissue from ~4-5 adults

• Exocrine cells secrete their product into a duct

Homeostasis • Works in conjunction w/

nervous system• slower to react/effects last

longer• endocrine glands include:

– pituitary, thyroid, parathyroid, adrenal, pineal, thymus, ORGANS - pancreas, gonads, hypothalamus (neuroendocrine organ), MINOR ORGANS - sm int., stomach, kidneys, heart, adipose cells

Paracrines

• locally acting chemicals that transfer information from cell to cell within single tissue– These are not considered hormones since

hormones are long-distance chemical signals

Hormone-target cell specificity

• A cell can only react to a H if it has a receptor on its plasma membrane or in its interior

• example: radio tuned to only pick up specific signals although there are many signals in the air concurrently

3 factors effecting target cell activation

• 1. Blood levels of the H

• 2. # of receptors for that H on or in target cells

• 3. affinity (strength) of bond b/t H & receptor– up-regulation - target cells form more receptors in

response to decreased blood H levels– down-regulation - prolonged exposure to high H [ ]

desensitizes the target cell by losing receptors so they respond less vigorously to H stimulation

Mechanism of Hormone action

• Hormones have their effect by altering cell activity, not causing the activity– alters plasma membrane permeability– alters membrane potential thru open/closing ion

channels– (+) synthesis of proteins/enzymes w/in cell– activates/deactivates enzymes– induces secretory activity– stimulates mitosis

Hormones

• Can be divided into 3 groups: – amino acid

derivatives

– peptide hormones

– lipid derivatives

Amino Acid Derivatives

• Small molecules structurally related to amino acids

• Synthesized from the amino acids tyrosine and tryptophan

Peptide Hormones

• Chains of amino acids

• Synthesized as prohormones:– inactive molecules converted to active hormones

before or after secretion

2 Groups of Peptide Hormones• Group 1:

– glycoproteins: • more than 200 amino acids long, with carbohydrate side chains:

– TSH, LH, FSH

• Group 2: – all hormones secreted by:

• hypothalamus

• hypophysis

• heart

• thymus

• digestive tract

• pancreas

2 Classes of Lipid Derivatives

• Eicosanoids: – derived from arachidonic acid

• Steroid hormones: – derived from cholesterol

Eicosanoids

• act locally so are not always thought of as Hs b/c they are not circulating in the blood

• examples:– leukotrienes - signaling chemicals that mediate

inflammation & some allergic reactions– prostaglandins - multiple functions including

raising of BP, enhancement of uterine contractions, blood clotting, & inflammation

Steroid Hormones • Are lipids structurally similar to cholesterol• Released by:

– reproductive organs– adrenal cortex (corticosteroids)– kidneys (calcitriol)

• Remain in circulation longer than peptide hormones

• Are converted to soluble form, are absorbed gradually by liver, & may be excreted in bile or urine

• Hormones circulate in the blood in two forms – free or bound– Steroids and thyroid hormone are attached to plasma

proteins and remain in circulation much longer– All others are unencumbered and remain functional

for less than one hour• These are either absorbed & broken down by liver or

kidneys, are broken down by enzymes, or diffuse out of the bloodstream to bind on target cells

Hormone Concentrations in the Blood

Mechanism of Hormone action

• A hormone must bind to a receptor to exert its effect

• There are two ways in which this happens– Second messenger mechanism– Using intracellular receptor

Catecholamines and Peptide Hormones

• Are not lipid soluble so unable to penetrate cell membrane

• Bind to receptor proteins at outer surface of cell membrane (extracellular receptors)

• Uses intracellular intermediary (second messenger) to exert effects

cAMP as a second messenger

Intracellular Intermediaries

• First messenger:– leads to second messenger– may act as enzyme activator, inhibitor, or cofactor – results in change in rates of metabolic reactions

• Important Second Messengers– Cyclic-AMP (cAMP):

• derivative of ATP

– Cyclic-GMP (cGMP): • derivative of GTP

– Calcium ions

Cascade Effect

• When the binding of a small number of hormone molecules to membrane receptors leads to thousands of second messengers in cell

• Magnifies effect of hormone on target cell

G Protein

• Enzyme complex coupled to membrane receptor• Involved in link between first messenger and

second messenger– Binds GTP

• Activated when hormone binds to receptor at membrane surface

• Changes concentration of second messenger cyclic-AMP (cAMP) within cell– Increased cAMP level accelerates metabolic activity

within cell

Lower cAMP Levels

1. Adenylate cyclase activity is inhibited

2. Levels of cAMP decline

3. cAMP breakdown accelerates & cAMP synthesis is prevented

Eicosanoids & Steroid Hormones• Are lipid soluble• Diffuse across membrane to

bind to receptors in cytoplasm or nucleus, activating or inactivating specific genes

• Alter rate of DNA transcription in nucleus:– change patterns of protein

synthesis

• Directly affect metabolic activity and structure of target cell

Endocrine reflex Triggers

• NEGATIVE FEEDBACK SYSTEM– humoral - PTH raises blood Ca, insulin,

aldosterone– neural - SNS to adrenals, oxytocin/ADH

release from post. pituitary due to hypothalamic (+)

– hormonal - “tropic” Hs from Ant. Pit. As a result of the target gland raising H levels in blood

Hypothalamus - a neuroendocrine organ

1. Secretes regulatory hormones: – Special hormones control endocrine cells in

pituitary gland

2. Contains autonomic centers:– Exert direct neural control over endocrine cells of

adrenal medullae

Pituitary gland aka Hypophysis

• Found in sella turcica• pea sized &

connected to hypothalamus via infundibulum

• secretes at least 9 Hs– Master gland

• anterior (glandular) & posterior (neural)lobes

Neurohypophysis • Derived from hypothalamic tissue

• Connected to the hypothalamus via the infundibulum

• Does not synthesize its own hormones– Stores those made in the hypothalamus

• Oxytocin & ADH

• Formed from epithelial tissue originating from Rathke’s pouch (oral mucosa)

• No neural connection to hypothalamus• Synthesizes its own hormones• Communicates via a vascular connection

– Primary capillary plexus in hypothalamus– Secondary capillary plexus in ant. pituitary

Adenohypophysis

Hypophyseal secretory effectors

Activity of the Adenophypophysis

• The hypothalamus sends a chemical stimulus to the anterior pituitary– Releasing

hormones stimulate the synthesis and release of hormones

– Inhibiting hormones shut off the synthesis and release of hormones

Adenohypophyseal Hormones

• Tropic hormones– 4 out of 6 are tropic (turn on/stimulatory)– TSH, ACTH, FSH, LH

– All adenohypophyseal Hs affect their target cells via a second messenger system

Thyroid stimulating hormone

• TSH…thyrotropin

• Release triggered by thyrotropin-releasing hormone (TRH)

• Somatostatin is released by hypothalamus w/ increasing TSH levels to block release

Adrenocorticotropic hormone

• ACTH…corticotropin

• Release triggered by corticotropin-releasing hormone (CRH)

• (+) adrenal cortex to release corticosteroid Hs; specifically those that help the body resist stressors

Gonadotropins • Follicle stimulating hormone (FSH)

– AKA follitropin– Stimulates gamete production (sperm & egg)

• Luteinizing hormone (LH)– AKA lutotropin– Promotes production of gonadal hormones– Stimulates maturation of the ovarian follicle and then

triggers ovulation– Stimulates interstitial cells of testes to produce

testosterone…AKA interstitial cell stimulating hormone (ICSH)

• Virtually non-existant in prepubescents• Release regulated by gonadotropin-releasing hormone

(GnRH) & suppressed by rising levels of gonadal Hs

Prolactin (PRL)• AKA mammotropin• Some people consider it a gonadotropin but structurally

similar to GH• Well documented to (+) milk production in breasts• May enhance testosterone production in males• Release controlled by both prolactin-releasing hormone

(PRH)…thought to be serotonin & prolactin-inhibiting hormone (PIH)…thought to be dopamine– PIH dominates in males– In women PRL levels rise & fall w/ estrogen levels (low

estrogen…(+) PIH release/high estrogen…(+) PRH…when just prior to menstruation accounts for breast swelling & tenderness

Growth hormone (GH)

• AKA Somatotropin (STH)

• Major targets are bone & sk mm cells– (+) most body cells to grow & divide– Encourages protein synthesis & use of fat for fuel

• Secretion is regulated by 2 hypothalamic Hs– Growth hormone-releasing hormone (GHRH)– Growth hormone-inhibiting hormone (GHIH)

• Aka somatostatin (also (-) other ant.pit. Hs, GI, & pancreatic secretions—both endo & exocrine)

Melanocyte Stimulating Hormone

• Also called melanotropin (MSH)

• Stimulates melanocytes to produce melanin

• Inhibited by dopamine

• Secreted during:– fetal development– early childhood– pregnancy– certain diseases

Table 18–2

Summary: The Hormones of the Pituitary Gland

Neurohypophyseal Hormones

• ADH & Oxytocin

• Both composed of 9 Aas & are almost identical– Differ in only 2 of 9 AAs

Antidiuretic hormone (ADH)• Inhibits or prevents urine formation• Hypothalamus has osmoreceptors to monitor blood

solute [ ] – If too [ ] ADH is released which causes kidneys to resorb

more water

– Other (+) include: pain, hypotension, nicotine, morphine

– (-) by alcohol & caffeine

• At high blood [ ] ADH has a vasoconstrictive effect…conditions such as severe blood loss cause ADH release which causes a rise in BP– Aka Vasopressin

Diabetes insipidus

• Deficiency of ADH• Leads to huge amounts of urine production• Insipidus = tasteless…no glucosuria• OK if thirst centers intact

– Dangerous in unconscious patients & w/head injury

– Head trauma victims must be carefully monitored

Oxytocin

• A strong stimulant of uterine contraction– Amounts higher during childbirth & w/nursing– Stretching of the uterus & cervix sends afferent

signals to the hypothalamus…release of more oxytocin

• Triggers milk “letdown” or ejection in lactating breasts ) from PRL

– Both are positive feedback mechanisms

Oxytocin, cont.• Natural & synthetic drugs (pitocin) are used

to induce labor & speed it up• Sometimes used to stop postpartum

bleeding (compressing of ruptures blood vessels)

• May play role in sexual satisfaction & orgasm in males & non-lacting females– May promote nurturing/affectionate behavior in

non-sexual relationships…cuddling hormone

Thyroid gland

• Butterfly shaped w/2 lobes connected by an isthmus• Made up of 2 types of cells

– Follicle cells (simple cuboidal or squamous epithelium) make up the follicle & produce a glycoprotein called thyroglobulin• The lumen of the follicle contains thyroglobulin w/

attached Iodine molecules• Thyroid hormone (TH) is produced from the

iodinated thyroglobulin– Parafollicular cells are interspersed b/t follicular

epithelium & the CT separating the follicles• Calcitonin is produced here

Thyroid Gland

Figure 18–10a, b

Thyroid Hormone (TH)• The body’s major metabolic hormone

• Actually 2 different Hs:– T4 or thyroxin (major H secreted by follicle

cells)– T3 or triiodothyronine (most formed at target

tissues by converting T4 to T3)

• Affects virtually every body cell except adult brain, spleen, testes, uterus, & the thyroid gland itself

TH, cont.• Stimulates enzymes concerned w/glucose

oxidation…increases BMR• Increases body heat production (calorigenic

effect)• Increases # of adrenergic receptors in BVs so it

is important in maintaining BP• Regulator of tissue growth & development (esp

skeletal, nervous, & reproductive system)also affects CV system, mm system, GI system, & hydration of skin

Synthesis of Thyroid Hormone

TH regulation• Falling thyroxin blood levels trigger release of

TSH…thyroxin• TSH levels are usually lower during the day, peak

just b/f sleep, & remain high during the night• Conditions that increase the body’s energy

requirements (pregnancy, prolonged cold) cause hypothalamus to release thyrotropin-releasing hormone (TRH)…TSH release from ant. pit. – TRH overcomes the (-) feedback controls

• Somatostatin, rising levels of glucocorticoids & sex Hs (estrogens & testosterone), & excessively high blood iodide [ ] all (-) TSH release

Thyroid disorders• Hypothyroid

– Myxedema – low BMR, feel cold, constipation, thick/dry skin, puffy eyes, edema, lethargy, mental sluggishness

• if it is a result of iodine insufficiency the thyroid gland enlarges to form a colloidal goiter (follicle cells produce colloid & store it but cannot iodinate it…TSH secretion increases…more colloid produced but no TH…after a while thyroid cells ‘burn out’ & gland atrophies)

– Cretinism – severe hypothyroid in infants; usually mentally retarded, short, disproportioned body, thick tongue; may be a genetic defect in thyroid or inadequate maternal dietary iodine intake

• Hyperthyroid– Grave’s disease – believed to be autoimmune; increased

BMR, sweating, rapid heart rate, nervousness, weight loss, exophthalmos (from edematous accumulation b/h eyes)

Exophthalmos Colloidal goiter

Calcitonin

• Produced by the parafollicular (C-clear) cells• Antagonist to PTH by lowering blood calcium levels

– (+) Ca uptake & incorporation into bone matrix

– (-) osteoclast activity…bone resorption

• Excessive blood Ca levels (~20% above normal) (+) calcitonin release

• Declining blood Ca levels (-) release• Seems more important in childhood w/rapidly

growing bones & rapidly changing blood Ca levels• In adults it is a weak hypocalcemic agent

Parathyroid glands

• Usually 4 BB sized glands found on the posterior aspect of the thyroid gland

• Secretion of PTH is by chief cells

• As many as 8 glands have already been found and some have even been found in other areas of the neck & thorax

Parathyroid hormone (PTH)

• AKA parathormone• Single most important H controlling Ca balance in

the blood• (+) from falling blood Ca levels• (-) from hypercalcemia• PTH release (+) 3 target organs…

PTH, cont.• PTH release (+)

– Osteoclasts – to digest bony matrix & release Ca & phosphates to the blood

– Kidneys – to enhance reabsorption of Ca (& excretion of phosphates)

– Intestine – increases absorption of Ca by intestinal mucosa cells… PTH causes conversion of vitamin D from the inactive form absorbed in the skin into its active form, calcitriol

• Vit D is needed to absorb Ca from ingested food

Adrenal glands• AKA suprarenal glands• Dual glands

– Adrenal medulla – nervous tissue (SNS)

– Adrenal cortex – glandular tissue derived from embryonic mesoderm; majority of gland

• All adrenal hormones help us cope with extreme (stressful) situations

Adrenal cortex• Produce over 2 dozen steroid Hs called corticosteroids• 3 distinct layers or zones of cells

– Zona glomerulosa – produce mineralocorticoids• Balance of water & minerals in body

– Zona fasciculata – produce glucocorticoids• Metabolism of body cells, gluconeogenesis, anti-inflammatory

– Zona reticularis – produce gonadocorticoids• Insignificant in adults, female libido?

• All corticosteroids are produced by some degree in all 3 layers

Mineralocorticoids • Aldosterone is the most potent (95% of total);

(+) distal tubules in kidneys to reabsorb Na ions from the forming urine & return them to bloodstream (same result of Na reabsorption from perspiration, saliva, & gastric juices)– Remember…where Na goes, water will follow– (+) of aldosterone secretion: hyperkalemia,

hyponatremia, decreasing blood volume & decreasing BP

– (-) of secretion is due to the reverse factors– ACTH has little to no effect on aldosterone release

Glucocorticoids

• Cortisol is the most important; help keep blood glucose levels constant w/sporadic meal patterns, very active responding to stress, anti-inflammatory– Secretion promoted by ACTH– Any stress will cause override of (-) feedback that

normally would reduce cortisol levels– Cortisol also enhances epinephrine’s

vasoconstrictive effects to increase BP…ensuring circulatory efficiency to help distribute nutrients

Glucocorticoids, cont.

• Excessive levels of cortisone:– Depress cartilage & bone formation– (-) inflammation by preventing vasodilation– Depresses the immune system– Promotes changes in cardiovascular, neural, & GI

function

– Frequently are the drug of choice for chronic inflammatory diseases

Cortisone diseases• Hypersecretion

– Cushing’s disease (syndrome) – most often results from overmedication; also adrenal cortex tumors or tumors of pituitary causing release of ACTH

• Hyperglycemia, loss of mm/bone protein, salt/water retention…”moon face”, “buffalo hump” from fat redistribution, easy bruising, poor wound healing…tx w/ discontinuing drugs or removal of tumor

• Hyposecretion– Addison’s disease – usually deficits of both glucocorticoids

(cortisone) & mineralocorticoids (aldosterone)• Weight loss, drop of plasma glucose & Na levels, rise in K levels…

dehydration, hypotension…tx w/corticosteroid replacement

Cushing Syndrome

Gonadocorticoids

• AKA sex hormones

• Most are androgens; testosterone is most important

• Minimal amounts of estrogen production

• Not much function in the adult…adrenal androgens seem to be related to the female sex drive (libido)– May convert to estrogens after menopause when

ovarian estrogens are no longer produced

Adrenal medulla

• Chromaffin cells are modified ganglionic sympathetic neurons that secrete the catecholamines– Epinephrine– Norepinephrine

Catecholamines • SNS fibers w/ fight or flight

– Blood sugar levels rise, vasoconstriction, tachycardia, diversion of blood from nonessential organs to brain, heart, & skeletal mm

• Catecholamines released after SNS (+) prolong response; response is brief in relation to effects of adrenocortical Hs

• 80% of Hs released are epi, 20% are norepi– Epi is more potent for (+) heart & metabolic activities– Norepi is more potent for (+)vasoconstriction & BP– Epi is often used clinically as a heart stimulant and a

bronchioldilator during asthma attacks

• Small gland hanging from the roof of the third ventricle of the brain

• Secretory product is melatonin• Melatonin is involved with:

– Inhibits reproductive functions– Protects against free radical formation– Day/night cycles & physiological processes that show

rhythmic variations (body temperature, sleep, appetite)

Pineal Gland

• A triangular gland, which has both exocrine and endocrine cells, located behind the stomach

• Acinar cells produce an enzyme-rich juice used for digestion (exocrine product)

• Pancreatic islets (islets of Langerhans) produce hormones (endocrine products)

• The islets contain four cell types:– Alpha () cells that produce glucagon

– Beta () cells that produce insulin

– Delta ( ) cells that produce somatostatin

– F-cells secrete pancreatic polypeptide (PP) – (-) g. bladder

Pancreas

Insulin • Produced by beta cells (islets of Langerhans)• Major effect is lowering of blood sugar; also

affects protein & fat metabolism• Insulin enhances membrane transport of glucose

into body cells like mm & fat cells…not liver, brain, & kidney tissue--these have easy access to glucose regardless of insulin levels

• Main (+) is hyperglycemia– Any hyperglycemic H can also (+) release: glucagon,

epi, GH, thyroxine, or glucocorticoids—all are called into action as blood glucose levels drop

Glucagon

• Produced by alpha cells (islets of Langerhans)

• Major target is the liver– Promotes glycogenolysis; gluconeogenesis from

lactic acid, fats & AAs

• 1 molecule of glucagon can cause the release 100 million molecules of glucose in to the blood

• Secretion (+) by falling blood sugar levels

• Secretion (-) by rise in blood sugar & somatostatin

Diabetes mellitus (DM)

• Hyposecretion or inactivity of insulin• 3 cardinal signs

– Polyuria – decreased blood volume & dehydration

– Polydipsia – thirst centers (+) from dehydration

– Polyphagia – b/c present glucose cannot be used & body starts breaking down fat & protein stores for energy metabolism

Gonads: Male• Testes located in an extra-abdominal sac (scrotum) produce

testosterone & Inhibin (sperm maturation)• Testosterone:

– Initiates maturation of male reproductive organs– Causes appearance of secondary sexual characteristics and sex drive– Is necessary for sperm production– Maintains sex organs in their functional state

• Paired ovaries in the abdominopelvic cavity produce estrogens and progesterone

• They are responsible for: – Maturation of the reproductive organs– Appearance of secondary sexual characteristics– Breast development and cyclic changes in the uterine mucosa

Gonads: Female

• Lobulated gland located deep to the sternum in the thorax

• Major hormonal product is thymosin

• This hormone is essential for the development of the T lymphocytes (T cells) of the immune system

Thymus

• Heart – produces atrial natriuretic peptide (ANP), which reduces blood pressure, blood volume, and blood sodium concentration

• Gastrointestinal tract – enteroendocrine cells release local-acting digestive hormones

• Placenta – releases hormones that influence the course of pregnancy

• Kidneys – secrete erythropoietin, which signals the production of red blood cells; & renin which is a powerful vasoconstrictor

• Skin – produces cholecalciferol, the precursor of vitamin D

• Adipose tissue – releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditure; resistin – reduces insulin sensitivity

Other Hormone-Producing Structures

• Four types of hormone interaction– Permissiveness – one hormone cannot exert its

effects without another hormone being present– Synergism – more than one hormone produces the

same effects on a target cell– Antagonism – one or more hormones opposes the

action of another hormone– Integration – hormones produce different &

complementary effects

Interaction of Hormones at Target Cells

General Adaptation Syndrome (GAS)

• AKA stress response

• How bodies respond to stress-causing factors

• Divided into 3 phases:

1.alarm phase

2.resistance phase

3.exhaustion phase

Figure 18–18

Alarm Phase

• Is an immediate response to stress directed by ANS

• Energy reserves mobilized (glucose)

• “Fight or flight” responses

• Dominant hormone is epinephrine

7 Characteristics of Alarm Phase

1. Increased mental alertness2. Increased energy consumption3. Mobilization of energy reserves (glycogen and lipids)4. Circulation changes:

– increased blood flow to skeletal muscles– decreased blood flow to skin, kidneys, and

digestive organs5. Drastic reduction in digestion and urine production6. Increased sweat gland secretion7. Increases in blood pressure, heart rate, and respiratory

rate

Resistance Phase

• Entered if stress lasts longer than few hours

• Dominant hormones are glucocorticoids

• Energy demands remain high

• Glycogen reserves nearly exhausted after several hours of stress

Effects of Resistance Phase

1. Mobilize remaining lipid and protein reserves

2. Conserve glucose for neural tissues

3. Elevate and stabilize blood glucose concentrations

4. Conserve salts, water, and loss of K+, H+

Exhaustion Phase

• Begins when homeostatic regulation breaks down

• Failure of 1 or more organ systems will prove fatal

• Mineral imbalance

Interactions between Endocrine and Other Systems

Figure 18–19