THE PARATHYROID GLANDS

◾ usually four glands,partially embedded in posterior surface of thyroid gland

◾ secrete parathyroid hormone (PTH)
◾ increases blood Ca2+ levels
◾ promotes synthesis of calcitriol
◾ increases absorption of Ca+
◾ decreases urinary excretion
◾ increases bone resorption
 THE ADRENAL GLANDS
◾ located on upper pole of kidney
◾ two regions
◾ adrenal medulla - inner core, 10% to 20% of gland
◾ cortex surrounds medulla & secretes several corticosteroids (hormones) from
three layers of glandular tissue
 THE ADRENAL MEDULLA
◾ acts as endocrine gland & a ganglion of sympathetic nervous system
◾ innervated by sympathetic preganglionic fibers
◾ modified sympathetic postganglionic neurons called chromaffin cells
◾ releases epinephrine & norepinephrine directly into the bloodstream
◾ increase alertness & prepare body for physical activity
◾ mobilize high-energy fuels,lactate,fatty acids,and glucose
◾ epinephrine inhibits insulin secretion - glucose-sparing effect
◾ muscles use fatty acids,saving glucose for brain
◾ increase BP,heart rate,blood flow to muscles,pulmonary airflow,and
metabolic rate
◾ decrease digestion & urine production
THE ADRENAL GLANDS
 THE ADRENAL C O RTEX

Zona glomerulosa (thin,outer layer)

◾ cells are arranged in rounded clusters
◾ secretes mineralocorticoids - regulate electrolyte balance
◾ Aldosterone stimulates Na+ retention & K + excretion

Zona fasciculata (thick,middle layer)

◾ cells arranged in fascicles separated by capillaries
◾ secretes glucocorticoids & androgens

Zona reticularis (narrow,inner layer)

◾ cells in branching network
◾ secretes glucocorticoids and sex steroids
 THE ADRENAL C O RTEX
◾ Glucocorticoids [ACTH]
◾ regulate metabolism of glucose and other fuels
◾ cortisol & corticosterone stimulate fat & protein catabolism, gluconeogenesis
(glucose from amino acids & fatty acids) & release of fatty acids & glucose into
blood
◾ help body adapt to stress & repair tissues
◾ anti-inflammatory effect becomes immune suppression with long-term use

◾ Cushing syndrome - excess cortisol secretion

◾ hyperglycemia,hypertension, weakness, oedema
◾ rapid muscle & bone loss due to protein catabolism
◾ abnormal fat deposition, moon face
 THE ADRENAL CO RTEX
◾ sex steroids or androgens:set libido;large role in prenatal male development
◾ estradiol: small quantity from adrenals, but this becomes important after
menopause for sustaining adult bone mass

Adrenogenital syndrome (AGS)

 adrenal androgen hypersecretion
 enlargement of external sexual organs in children
 early onset of puberty
 newborn girls exhibit masculinised genitalia
 masculinising effects on women
 increased body hair,deeper voice
https://www.slideshare.net/MuhammadSGhauri/cut-signs-androgenization
 THE PANCREAS
◾ A or alpha (α) cells of pancreatic islets secrete glucagon
◾ released between meals when blood glucose concentration is falling
◾ in liver,stimulates gluconeogenesis & release of glucose into circulation,
raising blood glucose level
◾ in adipose tissue, stimulates fat catabolism & release of free fatty acids
◾ glucagon also released to rising amino acid levels in blood,promotes amino
acid absorption & provides cells with raw material for gluconeogenesis
 THE PANCREATIC ISLETS
◾ Insulin secreted by B or beta (β) cells
◾ secreted during & after meal when glucose & amino acid blood levels are
rising
◾ stimulates cells to absorb these nutrients & store or metabolize them,
lowering blood glucose levels
◾ promotes synthesis glycogen,fat & protein
◾ suppresses use of already-stored fuels
◾ brain,liver,kidneys & RBCs absorb glucose without insulin,but other
tissues require insulin
◾ insufficiency or inaction is cause of diabetes mellitus
 THE PANCREATIC ISLETS
◾ Somatostatin secreted by D or delta (δ) cells
◾ partially suppresses secretion of glucagon and insulin
◾ inhibits nutrient digestion & absorption which prolongs absorption of
nutrients
◾ hyperglycemic hormones raise blood glucose concentration (includes hormones
from other glands)
◾ glucagon,growth hormone, epinephrine,norepinephrine, cortisol,and
corticosterone
◾ hypoglycemic hormones lower blood glucose
 ENDOCRINE FUNCTIONS OF OTHER ORGANS
◾ Skin
◾ keratinocytes convert a cholesterol-like steroid into cholecalciferol using UV
from sun

◾ Liver - involved in the production of at least five hormones

◾ converts cholecalciferol into calcidiol
◾ secretes angiotensinogen (a prohormone)
◾ precursor of angiotensin II (a regulator of blood pressure)
◾ secretes 15% of erythropoietin (stimulates bone marrow)
◾ source of IGF-I that controls action of growth hormone
◾ hepcidin:promotes intestinal absorption of iron
 ENDOCRINE FUNCTIONS OF OTHER ORGANS

◾ Kidneys - play role in production of three hormones

◾ convert calcidiol to calcitriol,the active form of vitamin D
◾ increases Ca2+ absorption by intestine & inhibits loss in the urine
◾ secrete renin that converts angiotensinogen to angiotensin I
◾ Angiotensin II created by converting enzyme in lungs
◾ constricts blood vessels & raises blood pressure
◾ produces 85% of erythropoietin
◾ stimulates bone marrow to produce RBCs
 ENDOCRINE FUNCTIONS OF OTHER ORGANS

◾ Heart
◾ natriuretic peptides in response to increase in blood pressure

◾ Stomach & small intestine secrete numerous enteric hormones secreted by

enteroendocrine cells
◾ coordinate digestive motility & glandular secretion
◾ cholecystokinin,gastrin,ghrelin
 ENDOCRINE FUNCTIONS OF OTHER ORGANS
◾ Adipose tissue secretes leptin - slows appetite
◾ Osseous tissue - osteocalcin secreted by osteoblasts
◾ increases number of pancreatic beta cells,pancreatic output of insulin,and
insulin sensitivity of body tissues
◾ inhibits weight gain & onset of type 2 diabetes mellitus
◾ Placenta
◾ secretes estrogen,progesterone
◾ regulate pregnancy,stimulate development of fetus and mammary glands
 LEARNING OUTCOMES
By the end of this lecture you should be able to:
◾ Define hormone and endocrine system.√
◾ Name the organs of the endocrine system. √
◾ Describe the relationships between the hypothalamus & pituitary gland. √
◾ List the hormones produced by the endocrine system and outline the main
targets and functions of each hormone.√
◾ Identify the chemical classes to which various hormones belong.
◾ Describe how hormones stimulate their target cells.
◾ O utline the stages of the stress response.
 HORMONE CHEMISTRY
◾ Hormones are derived from macromolecules

Three chemical classes: steroids, monoamines,and peptides

◾ Steroids
◾ derived from cholesterol
◾ sex steroids (e.g.oestrogen) from gonads & corticosteroids (e.g.cortisol)
from adrenal glands

◾ Monoamines (biogenic amines)

◾ made from amino acids
◾ catecholamines (dopamine,epinephrine,norepinephrine), melatonin,
thyroid hormone
 HORMONE CHEMISTRY

Peptides & glycoproteins

◾ created from chains of amino acids
◾ pituitary hormones & releasing &
inhibiting hormones from
hypothalamus
◾ insulin - large peptide hormone

(c) Peptides
 HORMONE SECRETION
◾ not secreted at steady rates - levels fluctuate throughout the day
◾ some are secreted on daily (circadian) rhythm
◾ some on a monthly rhythm (female ovarian cycle)
◾ others under the influence of stimuli that signify a need for them
◾ Neural stimuli
◾ Hormonal stimuli
◾ Humoral stimuli
 HORMONE SECRETION
◾ Neural stimuli
◾ nerve fibers supply some endocrine glands & elicit release of hormones
◾ SNS stimulates adrenal medulla to secrete epinephrine & norepinephrine in
situations of stress
◾ in childbirth,nerve signals originate from stretch receptors in uterus,travel
up spinal cord & brainstem to hypothalamus - stimulate release of oxytocin

◾ Hormonal stimuli
◾ hormones from hypothalamus regulate secretion by anterior pituitary gland
◾ pituitary hormones stimulate other endocrine glands to release hormones
 HORMONE SECRETION
◾ Humoral stimuli
◾ refers to blood-borne stimuli
◾ rising blood glucose concentration stimulates release of insulin
◾ low blood osmolarity stimulates secretion of aldosterone
◾ low blood calcium level stimulates secretion of parathyroid hormone
 HORMONE SECRETION
◾ peptide hormones & catecholamines are stored in secretory vesicles of endocrine
cells until needed
◾ released by exocytosis when cell receives a stimulus
◾ steroid hormones are released as they are synthesized by diffusion through cell
surface
◾ stimuli such as FSH &ACTH can increase synthesis & release of a steroid
hormone by several-fold within hours
◾ Thyroid hormone (TH) also diffuses freely through plasma membranes
◾ accumulates in extracellular spaces of gland waiting a stimulus
◾ TSH causes secretion
 HORMONE TRANSPO RT
◾ Most monoamines & peptides are hydrophilic
◾ mix easily with blood plasma
◾ Steroids & thyroid hormone are hydrophobic
◾ bind to transport proteins (albumins & globulins synthesized by the liver)
◾ bound hormones have longer half-life
◾ protected from liver enzymes & kidney filtration

◾ only unbound hormone leaves capillaries to reach target cell

◾ transport proteins protect circulating hormones from digestion by enzymes
in plasma & liver,and from being filtered out of the blood by the kidneys
 HORMONE RECEPTORS & MODE OF ACTION

◾ hormones stimulate only those cells that have receptors for them

◾ receptors are protein or glycoprotein molecules

◾ on plasma membrane,in the cytoplasm,or in the nucleus

◾ receptors ‘turn on’ metabolic pathways when hormone binds to them

◾ each target cell has several thousand receptors for a given hormone

◾ Receptor– hormone interactions exhibit specificity & saturation

◾ specific receptor for each hormone
◾ saturated when all receptor molecules are occupied by hormone molecules
 HORMONE RECEPTORS & MODE OF ACTION

◾ Peptide hormones
◾ cannot penetrate target cell
◾ bind to surface receptors & activate intracellular processes through second
messengers
◾ Steroid hormones
◾ penetrate plasma membrane & bind to internal receptors (usually in
nucleus)
◾ influence expression of genes of target cell
◾ take several hours to days to show effect due to lag for protein synthesis
 PLASMA MEMBRANE RECEPTORS
◾ Non-lipid soluble hormones (first messenger) cannot directly influence cell
activity
◾ need a messenger inside the cell (second messenger)
◾ second messenger changes the rates of metabolic reactions
◾ Second messengers:
◾ CyclicAMP (cAMP)
◾ Cyclic GMP (cGMP)
◾ Ca+ ions
 PLASMA MEMBRANE RECEPTORS
◾ G protein & cyclic-AMP (a derivative ofATP)
◾ many G proteins achieve effects by changing concentration of secondary
messenger [cyclic-AMP]
◾ results in increased cAMP levels - accelerates metabolic activity within the cell
◾ G proteins can
◾ open Ca+ ion channels
◾ release Ca+ ion stores

◾ 80% of prescription drugs target G protein-coupled receptors

 INTRACELLULAR RECEPTORS

◾ steroid hormones diffuse across lipid part

of plasma membrane
◾ bind to receptors in cytoplasm or nucleus
◾ hormone-receptor complexes then bind to
D N A - activate or deactivate genes
◾ change D N A transcription in nucleus & thus
translation & protein synthesis
 INTRACELLULAR RECEPTORS

Thyroid hormone
◾ transported across membrane
◾ binds to receptors in nucleus & activate genes
◾ binds to receptors on mitochondria &
acceleratesATP production
◾ this influences metabolic rate
H O RMONE RECEPTORS & MODE OF ACTION
PEPTIDES & C ATECHOLAMINES

1) Hormone-receptor binding
activates a G protein.

2) G protein activates adenylate cyclase.

3) Adenylate cyclase produces cAMP.

4) cAMP activates protein kinases.

5) Protein kinases phosphorylate enzymes.

This activates some enzymes & deactivates
others.

6)Activated enzymes catalyze metabolic

reactions with a wide range of possible
effects on the cell.
PEPTIDES & C ATECHOLAMINES

Various metabolic effects

H ormones Smooth muscle contraction
ADH Protein synthesis
TRH Secretion
OT Mitosis
LHRH
Catecholamines etc.
 PARACRINE SIGNALING
◾ Paracrine - chemical messengers that diffuse short distances & stimulate nearby
cells – local effects

◾ Histamine
◾ from mast cells in connective tissue - causes relaxation of blood vessels

◾ Nitric oxide
◾ from endothelium of blood vessels - causes vasodilation

◾ Catecholamines
◾ diffuse from adrenal medulla to cortex

◾ Autocrines - chemical messengers that stimulate same cell that secreted them

◾ single chemical can act as a hormone, paracrine,or even neurotransmitter in

different locations
 MODULATION OF TARGET-CELL SENSITIVITY

◾ target-cell sensitivity adjusted by changing

number of receptors

◾ up-regulation: number of receptors increased

◾ sensitivity is increased
Low receptor density Increased receptor density Stronger response
Weak response Increased sensitivity

(a) Up-regulation

◾ down-regulation reduces number of receptors

◾ cell less sensitive to hormone
◾ occurs with long-term exposure to high
hormone concentrations
High receptor density Reduced receptor density D iminished response
Strong response Reduced sensitivity
 HORMONE INTERACTIONS
◾ most cells sensitive to more than one hormone & exhibit interactive effects
◾ Synergistic effects
◾ multiple hormones act together for greater effect
◾ synergism between FSH & testosterone on sperm production
◾ Permissive effects
◾ hormone enhances target organ response to a second later hormone
◾ oestrogen prepares uterus for action of progesterone
◾ Antagonistic effects
◾ hormone opposes the action of another
◾ insulin lowers blood glucose & glycogen raises it
ANTAGONISTIC EFFECTS OF INSULIN & GLUCAGON O N LIVER

Figure 17.23
Copyright © McGraw-Hill Education. Permission required for reproduction or display.
 HORMONE CLEARANCE
◾ hormone signals must be turned off when they have served their purpose
◾ most hormones are taken up & degraded by liver & kidney
◾ excreted in bile or urine

◾ Metabolic clearance rate (MCR)

◾ rate of hormone removal from the blood
◾ half-life:time required to clear 50% of hormone from the blood
◾ the faster the MCF,the shorter the half-life
 LEARNING OUTCOMES
By the end of this lecture you should be able to:
◾ Define hormone and endocrine system.√
◾ Name the organs of the endocrine system. √
◾ Describe the relationships between the hypothalamus & pituitary gland. √
◾ List the hormones produced by the endocrine system and outline the main
targets and functions of each hormone.√
◾ Identify the chemical classes to which various hormones belong. √
◾ Describe how hormones stimulate their target cells. √
◾ O utline the stages of the stress response.
 STRESS &ADAPTATION
• Stress - situation that disturbs homeostasis
◾ can threaten physical or emotional well-being
◾ injury,surgery, infection,intense exercise, pain,grief,depression, anger,etc. General adaptation
syndrome (GAS)

◾ consistent way the body reacts to stress

◾ typically involves elevated levels of epinephrine & glucocorticoids
• (especially cortisol)
◾ Occurs in three stages
• Alarm reaction
 THE ALARM REACTION
◾ Initial response
◾ mediated by norepinephrine from SNS & epinephrine from adrenal medulla
◾ prepares body for fight or flight
◾ stored glycogen is consumed
◾ increases aldosterone & angiotensin levels
◾ Angiotensin helps raise blood pressure
◾ Aldosterone promotes Na+ & H 2O conservation
 THE STAGE OF RESISTANCE
◾ after a few hours, glycogen reserves gone, but brain still needs glucose
◾ provide alternate fuels for metabolism
◾ stage dominated by cortisol
◾ hypothalamus secretes corticotropin-releasing hormone (CRH)
◾ pituitary secretesACTH
◾ stimulates the adrenal cortex to secrete cortisol and other glucocorticoids
◾ promotes breakdown of fat & protein into glycerol,fatty acids,and amino
acids for gluconeogenesis
 THE STAGE OF RESISTANCE
Cortisol has glucose-sparing effect
◾ inhibits protein synthesis leaving free amino acids for gluconeogenesis
◾ Adverse effects of excessive cortisol:
• depresses immune function
• increases susceptibility to infection and ulcers
• lymphoid tissues atrophy,antibody levels drop & wounds heal poorly
 THE STAGE OF EXHAUSTION
◾ if stress continues over months & fat reserves are gone, homeostasis is
overwhelmed
◾ often marked by rapid decline and death
◾ protein breakdown & muscle wasting
◾ loss of glucose homeostasis because adrenal cortex stops producing
glucocorticoids

◾ Aldosterone promotes H 2 O retention & hypertension

◾ conserves Na + & promotes elimination of K+ and H+
◾ hypokalemia & alkalosis can result in death
◾ death can be due to heart & kidney infection or overwhelming infection
 ANTI-INFLAMMATORY DRUGS
◾ Cortisol & corticosterone
◾ Steroidal anti-inflammatory drugs (SAIDs)
◾ inhibit inflammation by blocking release of arachidonic acid from plasma
membrane & inhibit synthesis of eicosanoids
◾ Disadvantage - produce symptoms of Cushing syndrome
◾ Aspirin,ibuprofen & celecoxib (Celebrex)
◾ N onsteroidal anti-inflammatory drugs (NSAIDs)
◾ useful in treatment of fever & thrombosis
◾ inhibit prostaglandin & thromboxane synthesis
 LEARNING OUTCOMES
By the end of this lecture you should be able to:
◾ Define hormone and endocrine system.√
◾ Name the organs of the endocrine system. √
◾ Describe the relationships between the hypothalamus & pituitary gland. √
◾ List the hormones produced by the endocrine system and outline the main
targets and functions of each hormone.√
◾ Identify the chemical classes to which various hormones belong. √
◾ Describe how hormones stimulate their target cells. √
◾ O utline the stages of the stress response. √