The Endocrine System

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Chapter 18

• The Endocrine System

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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

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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

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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

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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

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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

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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

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Hormones

• Can be divided into 3 groups
• amino acid derivatives
• peptide hormones
• lipid derivatives

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Amino Acid Derivatives

• Small molecules structurally related to amino
  acids
• Synthesized from the amino acids tyrosine and
  tryptophan

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Peptide Hormones

• Chains of amino acids
• Synthesized as prohormones
• inactive molecules converted to active hormones
  before or after secretion

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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

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2 Classes of Lipid Derivatives

• Eicosanoids
• derived from arachidonic acid
• Steroid hormones
• derived from cholesterol

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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

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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

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Hormone Concentrations in the Blood

• 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

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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

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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

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cAMP as a second messenger
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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

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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

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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

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Lower cAMP Levels

• Adenylate cyclase activity is inhibited
• Levels of cAMP decline
• cAMP breakdown accelerates cAMP synthesis is
  prevented

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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

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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

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Hypothalamus - a neuroendocrine organ

• 1. Secretes regulatory hormones
• Special hormones control endocrine cells in
  pituitary gland
• Contains autonomic centers
• Exert direct neural control over endocrine cells
  of adrenal medullae

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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

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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

Adenohypophysis

• Formed from epithelial tissue originating from
  Rathkes 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

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Hypophyseal secretory effectors
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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

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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

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Thyroid stimulating hormone

• TSHthyrotropin
• Release triggered by thyrotropin-releasing
  hormone (TRH)
• Somatostatin is released by hypothalamus w/
  increasing TSH levels to block release

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Adrenocorticotropic hormone

• ACTHcorticotropin
• Release triggered by corticotropin-releasing
  hormone (CRH)
• () adrenal cortex to release corticosteroid Hs
  specifically those that help the body resist
  stressors

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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 testosteroneAKA interstitial cell
  stimulating hormone (ICSH)
• Virtually non-existant in prepubescents
• Release regulated by gonadotropin-releasing
  hormone (GnRH) suppressed by rising levels of
  gonadal Hs

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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() PRHwhen just prior to menstruation
  accounts for breast swelling tenderness

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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 secretionsboth endo exocrine)

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Melanocyte Stimulating Hormone

• Also called melanotropin (MSH)
• Stimulates melanocytes to produce melanin
• Inhibited by dopamine
• Secreted during
• fetal development
• early childhood
• pregnancy
• certain diseases

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Summary The Hormones of the Pituitary Gland
Table 182
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Neurohypophyseal Hormones

• ADH Oxytocin
• Both composed of 9 Aas are almost identical
• Differ in only 2 of 9 AAs

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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
  effectconditions such as severe blood loss cause
  ADH release which causes a rise in BP
• Aka Vasopressin

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Diabetes insipidus

• Deficiency of ADH
• Leads to huge amounts of urine production
• Insipidus tastelessno glucosuria
• OK if thirst centers intact
• Dangerous in unconscious patients w/head injury
• Head trauma victims must be carefully monitored

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Oxytocin

• A strong stimulant of uterine contraction
• Amounts higher during childbirth w/nursing
• Stretching of the uterus cervix sends afferent
  signals to the hypothalamusrelease of more
  oxytocin
• Triggers milk letdown or ejection in lactating
  breasts ) from PRL
• Both are positive feedback mechanisms

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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 relationshipscuddling hormone

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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

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Thyroid Gland
Figure 1810a, b
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Thyroid Hormone (TH)

• The bodys 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

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TH, cont.

• Stimulates enzymes concerned w/glucose
  oxidationincreases 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

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Synthesis of Thyroid Hormone
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TH regulation

• Falling thyroxin blood levels trigger release of
  TSHthyroxin
• TSH levels are usually lower during the day, peak
  just b/f sleep, remain high during the night
• Conditions that increase the bodys 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

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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 itTSH secretion increasesmore
  colloid produced but no THafter 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
• Graves disease believed to be autoimmune
  increased BMR, sweating, rapid heart rate,
  nervousness, weight loss, exophthalmos (from
  edematous accumulation b/h eyes)

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Exophthalmos
Colloidal goiter
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Calcitonin

• Produced by the parafollicular (C-clear) cells
• Antagonist to PTH by lowering blood calcium
  levels
• () Ca uptake incorporation into bone matrix
• (-) osteoclast activitybone 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

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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

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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

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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

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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

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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

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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)
• Rememberwhere 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

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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 epinephrines
  vasoconstrictive effects to increase BPensuring
  circulatory efficiency to help distribute
  nutrients

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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

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Cortisone diseases

• Hypersecretion
• Cushings 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 retentionmoon face, buffalo hump
  from fat redistribution, easy bruising, poor
  wound healingtx w/ discontinuing drugs or
  removal of tumor
• Hyposecretion
• Addisons disease usually deficits of both
  glucocorticoids (cortisone) mineralocorticoids
  (aldosterone)
• Weight loss, drop of plasma glucose Na levels,
  rise in K levelsdehydration, hypotensiontx
  w/corticosteroid replacement

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Cushing Syndrome
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Gonadocorticoids

• AKA sex hormones
• Most are androgens testosterone is most
  important
• Minimal amounts of estrogen production
• Not much function in the adultadrenal androgens
  seem to be related to the female sex drive
  (libido)
• May convert to estrogens after menopause when
  ovarian estrogens are no longer produced

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Adrenal medulla

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

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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

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Pineal Gland

• 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)

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Pancreas

• 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

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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 cellsnot 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
  glucocorticoidsall are called into action as
  blood glucose levels drop

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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

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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

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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

Gonads Female

• 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

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Thymus

• 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

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Other Hormone-Producing Structures

• 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

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Interaction of Hormones at Target Cells

• 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

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General Adaptation Syndrome (GAS)

• AKA stress response
• How bodies respond to stress-causing factors
• Divided into 3 phases
• alarm phase
• resistance phase
• exhaustion phase

Figure 1818
75
Alarm Phase

• Is an immediate response to stress directed by
  ANS
• Energy reserves mobilized (glucose)
• Fight or flight responses
• Dominant hormone is epinephrine

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7 Characteristics of Alarm Phase

• Increased mental alertness
• Increased energy consumption
• Mobilization of energy reserves (glycogen and
  lipids)
• Circulation changes
• increased blood flow to skeletal muscles
• decreased blood flow to skin, kidneys, and
  digestive organs
• Drastic reduction in digestion and urine
  production
• Increased sweat gland secretion
• Increases in blood pressure, heart rate, and
  respiratory rate

77
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

78
Effects of Resistance Phase

• Mobilize remaining lipid and protein reserves
• Conserve glucose for neural tissues
• Elevate and stabilize blood glucose
  concentrations
• Conserve salts, water, and loss of K, H

79
Exhaustion Phase

• Begins when homeostatic regulation breaks down
• Failure of 1 or more organ systems will prove
  fatal
• Mineral imbalance

80
Interactions between Endocrine and Other Systems
Figure 1819