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A&P- CH 18 Endocrine System

Homeostasis
preserved and coordinated by intercellular communication
Nervous system
fast; seconds (short-term)
uses electrical impulses; synaptic communication (neurotransmitters)
short lived bc broken down quickly
effects specific muscles and glands
Endocrine system
slow; hours or decades (long-term)
uses chemical messengers (hormones)
sustained, long-term basis
much broader effect
Indirect communication
involves release and receipt of chemical messengers; cells “talk” to each other by releasing chemicals into the extracellular fluid= paracrine communication/local hormones
ex: prostaglandins which diffuse out of tissue
Direct communication
b/w 2 cells in direct physical contact
-rarer (gap junctions)
Neural communication
immediate response (crisis management); short term effects
delivery: at synapse by NT -> action potentials
Endocrine communication
slow response; long term effects; gradual (growth)
delivery: in bloodstream by hormones (chemicals produced in one tissue w/ effects elsewhere..target cells w/ receptors)
Paracrine communication
release of factors (chem. structure not known)
ex: interleukin 2- released by T cell that activates nearby immune cells
NO (nitrous oxide)
released by endothelial cells lining blood vessels; releases smooth muscle causing vasodilation. Drug- viagra or blood pressure drugs
delivery: diffusion through extracellular fluid; limited to immediate areas
Direct communication
gap junctions allow passage of ions and small mol. (lipid soluble); limited to adjacent cells
Similarities of endocrine and NS
-both rely on release of chemicals that bind to specific receptors
-share many of chem messengers; norepinephrine and epinephrine called hormones when released into bloodstream and neurotransmitters when released across synapse
-controlled through neg feedback systems
-preserve homeostasis by coordinating and reg activities of other cells, tissues, organs and systems
Endocrine cells
ductless secretions released into extracellular fluids (interstitial)-> blood -> target cell -> specific receptor
1. hormones ( long distance)
2. paracrine factors (short distance)
Exocrine cells
secretions occur through ducts; deposited where it needs to act:
dig: salivary gland -> saliva
sudoriferous glands, sebaceous glands, mucous glands
hormones; endocrine communication
release of chemicals that are released from one tissue and transported in the bloodstream to alter the activities of specific cells in other tissues
hormone
substance with effects outside its tissue of origin if its chemical structure is known
factor
if structure remains to be determined
hormones
have target cells that contain specific receptors that bind and “read” the hormonal message that alters the “behavior” of that cell
Role of hormone receptors
hormones only affects specific target cells by chemically binding to specific ptn receptors (only target cells for a given hormone have receptors that bind and recognize that hormone)
target cells have 2000-100,000 receptors for particular hormone which are constantly being synthesized and broken down (turnover)
Down-regulation
if too much hormone is circulating, receptor numbers decrease (cell is less sensitive)
Up-regulation
if too little hormone is circulating, then makes more receptors making cell more sensitive to the hormone
Drugs & hormones
certain drugs act as synthetic hormones, blocking the receptors from a naturally occuring hormone
Ex: mimic Ex RU486 induces abortion by binding to receptors for progesterone that prepares uterus for implantation of egg; taxol drugs mimic estrogen
Hormone action
hormones act as chem messengers that act on specific target tissue/cells to bring about a second type of internal coordination
-bind strongly w/ specific ptns called receptors; presence or absence of diff receptors determines cells hormonal sensitivity and response
Target cell specificity of hormones
though a hormone reaches every part of the body, each hormone acts only on one type of target cell w/ specific protein receptors
half life of hormone
hormones released into blood, hormone remains active only for a short period; some last only few seconds, others up to a few hours
at end of period is degraded by cellular enzymes, or by liver or kidney
Mechanisms of hormone action
hormones interact w/ appropriate receptor (ptn molecule) on membrane of target cell
-every cell has receptors for responding to several different hormones but cells of diff tissues have diff combinations of receptors
hormonal sensitivities
hormones have differential effects on specific tissues
Hormone receptors found on:
plasma membrane (outer surface= extracellular receptors)
catecholamines (E, NE, dopamine)- peptide hormones; not lipid soluble, unable to penetrate plasma membrane
-inside the cell (inner surface= intracellular receptors)- eicosanoids
Hormones
alter the operations of target cells by changing type, quantities, or activities of important enzymes and structural proteins in many cells simultaneously
Hormone function
-synthesis of an enzyme or structural protein not present by activating genes in nucleus
-increase or decrease rate of synthesis of protein or enzyme by changing the rate of transcription or translation
-turn an existing membrane channel or enzyme channel “on” or “off” by changing its shape or structure
Pheromones
effect other people through olfactory mechanism
Prostaglandins
effect the next cell (paracrine); stimulate contractions in smooth muscle tissue (intestines, uterus, female reproductive tract, ductus deferens (ejaculation of semen), stimulates homeostasis= blood clotting, stimulates inflammation response, vasodilation, capillary permeability)
NSAIDs- nonsteroid anti-inflammatory drugs
inhibit prostaglandins synthesis by binding to the prostaglandins
1. Ibuprofen= motrin, nuprin, advil
2. aspirin
3. naproxen= aleve
4. ketoprofen= arudis KT
Amino acid derivatives
small molecules structurally related to amino acid- catecholamines
synthesized from amino acid
Tyrosine- aa derivative
1. thyroid hormones; insulin
2. epinephrine, norepineprine, dopamine
Trytophan- aa derivative
melatonin and serotonin
Peptide hormones
chains of aa that are inactive (prohormones) -> active hormones glycoproteins: 200+ aa w/ carb side chain
– TSH- thyroid stimulating hormone (glycoprotein)
– LH- luteinizing hormone
– FSH- follicle stimulating hormone
Short peptide chains
ADH: antidiuretic hormone
oxytocin
GH- growth hormone
PRL- prolactin
Lipid derivatives
eicosanoids- 20 C fatty acid w/ 5 C ring at one end
1. leukotrienes- released by WBC in response to injury or disease
2. prostaglandins- coordinates cellular activities

steroids- derived from cholesterol; in blood bound to specific transport ptns which liver removes released by reproductive organs
-androgens by testis
-estrogen and progesterone by ovaries
by suprarenal glands (coricosteroids), by kidneys

Freely circulating hormones
remain functional for less than one hour and sometimes as little as 2 minutes
Thyroid and steroid hormones
circulate the longest bc get attcahed to special transport proteins
Inactivation occurs:
-diffuse out of bloodstream and bind to target cells
– breakdown by enzymes in the plasma or interstitial fluid
– absorption and breakdown by liver or kidney
Amino acid based hormones
hydrophilic- can’t cross the cell membrane unless there is a membrane bound receptor
Steroid hormones
hydrophobic- CAN cross the cell membrane by using a cytoplasmic receptor
2 diff ways 2 groups of hormones influence target cell chemistry:
1. by using second messenger
2. by direct gene action
Amino acid based hormones cont.
do not enter target cells, instead bind extracellular, with receptors on plasma membrane of target cells
1. made of single aa (glycine, glutamate)
2. short chain of aa (peptide hormones)
3. long chain of aa (insulin, growth hormone)
Steroid hormones cont.
derived from cholesterol and as they are lipid soluble, can enter target cells by diffusion and bind w/ intracellular receptors of target cells
these 2 hormones alter target cell chemistry:
1. changing membrane potential, and causing ion flow into or out of target cells
2. activating or deactivating cellular enzymes
3. inducing ptn synthesis in target cells
4. inducing secretory activity of target cells
5. initiating mitotic division
Hormone activity
hormones that bind to receptors on plasma membrane must use an intracellular intermediary to effect the cell
– first messenger->second messenger-> activates enzyme, acts as inhibitor or cofactor, changes rate of various metabolic rxns
Important second messengers
cyclic AMP (cAMP)- derivative of ATP
clyclic GMP (cGMP)
calcium ions
G-protein
link b/w first messenger and second messenger usually involves this protein which binds GTP
– 80% prescription drugs target G protein-coupled receptors
amplification
binding of small number of hormone molecules to mem receptors may lead to appearance of many thousands of second messengers in cytoplasm
receptor cascade
release of more than one kind of second messenger produces a linked sequence of enzymatic rxns
G-protein activation
when water-soluble hormone molecule (most amino-acid based hormones, cept thyroid hormones) binds with receptor on plasma membrane of target cell
adenylate cyclase
activated when G-protein is activated; acts on ATP in target cell and releases cAMP which acts as a second messenger and initiate variety of cehm changes in target cell
Protein kinases
perform protein phosphorylations which can open ion channels inducing and regulating diff types of chem rxns that ultmately result in formation of millions of new molecules inside target cell
G proteins can also effect:
Ca++ ions influx either from intracellular stock piles or by opening Ca++ channels
G ptn activates phospholipase C (PLC) -> DAG & IP3= -> PKC (ptn kinase C) -> phosphorylation of ca ++ channels -> inc Ca++ calmodulin -> necessary stimulation by epinephrine or noradrenaline (or oxytocin)
Direct gene action
steroid hormones; lipid-soluble; enter target cell to bind w/ intracellular receptors
bind w/ intracellualr receptors, these hormones induce ptn synthesis, binding to DNA initiating transcription and translation of specific genes
Endocrine activity triggered by:
1. humoral stimuli: changes in composition or entracellular fluid
2. hormonal stimuli: arrival or removal of specific hormone
3. neural stimuli: arrival of neurotransmitter at neuro-glandular junctions
Control of endocrine activity
endocrine activity regulated by changing amount of hormone secreted and pattern of hormone release (pulses vs continuous) through neg feedback
Humoral stimuli
humor means fluid; changes in composition of body fluid act as stimuli inducing endocrine gland to release hormone
Ex: increase in blood sugar from optimum- relase of insulin; decrease in blood calcium level causes release of PTH
Neural stimuli
nerve stimulus directly causes release of hormones
Ex: under stress, sympathetic nerve endings stimulate adrenal medulla to release epinephrine and norepinephrine
Hormonal stimuli
a hormone of one gland stimulates another endocrine gland
Ex: thyroid stimulating hormone from anterior pituitary gland stimulates thyroid gland to release thyroid hormone
Main endocrine glands
-pituitary gland (hypophysis cerebrii)
-hypothalamus- neuroendocrine center
-thyroid glands
-parathyroid glands
-adrenal glands: thymus gland, pineal gland, gonads
Contain ells that secrete hormones
hypothalamus, thymus, islets of langerhans in pancreas, ovaries, testis, kidneys, stomach, liver, small intestine
Pituitary and hypothalamus
“master gland”- hypothalamus: 9 diff hormones
pituitary: secretes seven
-play major role in reg of all aspects of growth, dev, metabolism, and homeostasis
Pituitary gland
suspended from hypothalamus by stalk called infundibulum, located in sella turcica of sphenoid bone
Neurohypohysis
posterior lobe; non secretory part, made of glial cells and nerve fibers
-stores neuro-hormone produced by hypothalamus
Adenohypophysis
anterior lobe; made of endocrine cells that produce # of hormones
Hormones by anterior pituitary lobe
1. growth related hormones
2. tropic hormones or tropins
3. prohormone (POMC) from which a few active hormones are derived

-all are amino acid-based hormones

Growth hormone/Somatotropin
released when growth hormone releasing hormone (GHRH) from hypothalamus stimulates endocrine cells in anterior pituitary lobe
hypothalamus->releases GHRH->stimulates anterior pituitary->releases GH->acts on growth plate->stimulates cartilage cells to divide and increase in number= longitudinal bone growth
growth hormone inhibiting hormone (GHIH)/somatostatin
growth hormone production is stopped
GH function
promotes body growth by ptn synthesis; promotes fat utilization by body cells
Somatomedins
produced by muscles, bones, liver; GH reg aa metabolism and sulfur intake and use by cartilage cells
Pituitary gigantism/ acromegaly
oversecretion of GH
Pituitary dwarfism
hyposecretion of GH
Prolactin
stimulates female milk glands after child birth and in other vertebrates stimulates reproductive organs
TSH/thyroid stimulating hormones or thyrotropins (tropic hormone)
stimulates thyroid glands
TRH(from hypothalamus)->stimulates AP->releases TSH->stimulates thyroid glands= releases thyroid hormones
ACTH/adrenocorticotropic hormone or corticotropin (tropic hormone)
stimulates adrenal cortex
CRH(from hypothalamus)->stimulates AP->releases ACTH->stimulates adrenal cortex-= releases corticosteroid hormones
Gonadotropins
stimulates primary sex organs (testis and ovaries)
FSH-follicle stimulating hormone (gonadotropin)
stimulates sex cell production by testis/ovary at puberty
Luteinizing hormone (LH) (gonadotropin)
intiates sex hormones production released by testis and ovary; testis produces testosterone and ovary produces estrogen and progesterone; LH help reg ovulation in females
GnRH-> stimulates AP->releases FSH and LH-> stimulates ovary/testis=sperm and ovum prod. and release of testosterone/estrogen + progesterone at puberty
POMC
large protein based molecules
Pro-hormone POMC (pro opiomelanocortin)
may yield as many as 10 biologically active peptides involved in diverse cellular functions
ACTH: adrenocorticotropic hormone
binds to mem receptors activating G protein; cAMP that stimulates secretion of cortisol from adrenal cortex
MSHs: melanocyte-stimulating hormone
different tissues (hypothalamus, placenta, epithelium); all cleavage sites may be used, giving rise to peptides with pain and energy homeostasis, melanocyte stimulation, immune modulation
Melanocytes
unicellular glands, located in stratum basal of epidermis, produce melanin (pigment) stim by UV rays that act on hypothalamus
Endorphins
body’s natural pain killers; same effect as opiates during stress and exercise
Lipotrophins
bind to receptors on adipose mem causing lipid breakdown and release of FA into blood
Hypothalamus
part of brain, neurohypohysis; control pituitary gland; acts as nerve center for hormone fxns; produces ADH and oxytocin
ADH
released when water content in body decreases; causes more water absorption at kidneys, results in reduced urine volume; may also cause increase blood pressure (vasopressin)
Oxytocin
effects smooth muscles, uterine contractions, ejaculation; “let down” reflex by which milk is ejected from milk glands; “cuddling hormone” plays role in pair bonding and affectionate behavior; sexual arousal
T4- tetra-iodo thyronine/thyroxine
has thyroglobulin and 4 atoms of iodine
T3 or tri-iodothyronine
has thyrogloblin and 3 atoms of iodine
Thyroid hormones
called metabollic hormones; help reg cell metabolism by reg oxygen and nutrient use by most body cells
Hypothyroidism
in adults leads to myxedema- edema, lethargy, sluggishness, obesity; if caused by iodine deficiency- goiter; can lead to cretinism in children
Hyperthyroidism
in adults leads to Grave’s disease (autoimmune disorder)
parafollicular cells of thyroid glands (c-cells)
produce second hormone called calcitonin
-released when blood calcium level increases; inhibits osteoclasts and stimulates osteoblasts to promote bone formation; important in starvation and late stages of preg.
Parathyroid glands
-2 pairs of small glands on posterior side of thyroid glands
-produces PTH
-released when blood calcium level decreases
-stimulates osteoclasts and causes bone resorption
-causes calcium absorption from kidneys and intestine
-activates Vit D to enhance calcium absorption
Adrenal cortex
made of endocrine cells that produce number of steroid hormones called corticosteroids
inner adrenal medulla
consists of modified sympathetic neurons which together produce 2 important amino-acid based hormones called catecholamines
Addison’s disease
hyposecretion of glucocorticoids and aldosterone (majority autoimmune disorders where antibodies cause adrenal cortex destruction/ block ACTH to receptors)
Mineralocorticoids
help reg electrolytes (mineral salt) conc. in body fluids, esp Na+ and K+
Aldosterone
most important mineralocorticoid; promotes sodium absorption from kidneys and intestine; sodium reg coupled w/ potassium ion reg; as sodium ions absorbed, potassium ions excreted from body
also reg bicarbonate ion, hydrogen ions, and chloride ions
Glucocorticoids
cortisol= most important glucocorticoid; helps reg blood glucose level on 24 hr cycle and induces hyperglycemia
stress hormone
high blood glucose level; when body is under stress; increases blood pressure causing vasoconstriction; cortisol helps resist stress
Gonadocorticoids
similar to male sex hormones produced by sex glands; supposed to help in dev. of sex organs before onset of puberty
Adrenal medulla
responds to short-term stress by releasing catecholamines
epinephrine and norepinephrine
Epinephrine
makes up 80% adrenal medulla secretion; increases heart rate and rate of blood flow; dilates air passage in lungs; helps increase level of activity of most organs
Norepinephrine
causes vaso-constriction of peripheral arterioles; increases bp
Fight or flight system
quickly mobilizes body resources against danger (brings glucose and O2 to organs); inhibits dig (reduces blood to kidney, release renin)
Eventual exhaustion
eventual wasting of muscles, suppression of immune system, ulceration of gastrointestinal tract, failure of pancreatic beta cells-> disease
Exocrine, acinar cells
in pancreas; produce dig enzymes poured into small intestine through pancreatic duct
Endocrine cells
in pancreas; organized as small plated islands, in b/w lobes of acinar cells, called islets of langerhans
consist of: alpha cells, beta cells, delta cells
alpha cells
produce glucagon
beta cells
produce insulin
delta cells
produce somatostatin
Polyuria
increased urine volume; kidneys use large volumes of water to remove unused glucose from blood; body also loses large quantities of sodium and potassium ions
Polydipsia
water loss from kidneys leads to dehydration and intense thirst
Polyphagia
acute hunger; as body cells can’t use blood glucose in absence of insulin
Pineal gland
contain neurons, neuroglial and pinealocytes which synthesize melatonin from molecules of neurotransmitte serotonin
fxn of pineal gland
melatonin plays role in timing of human sexual maturation; protects against damage by free radicals; setting of circadian rhythms
Thymus gland
large lymphoid organ w/ some endocrine cells; produce thymosins; hormones that reg maturation of T-lymphocytes
Granulocytes
neutrophil- make up 70%, eosinophils, basophils
Agranulocytes
monocytes, lymphocytes
B cells
responsible for antibody mediated immunity= humoral immunity
T cells
responsible for cell mediated immunity
Gonads
produce sex hormones (steroid hormones)
Estrogen
female hormone that reg maturation of reproductive organs and secondary sexual traits of females at puberty
Progesterone
pregnancy hormone that reg all changes in female body during preg
Testosterone
reg maturation of male sex organs and male secondary sexual traits

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