ch 17- endocrine system

endocrine system

comp of ductless glands that synthesize + secrete hormones

• hormones released into blood

target cells

have specific receptors for a hormone

• bind hormone + respond

steps to hormone transport → target cells

hormones released → interstitial fluid→ blood→ transported w/in blood → leave blood + enter interstitial fluid → hormone binds to t. cell receptors

ligands

chemical messengers

• bind to cellular receptor on t. cell

how does it differ from nervous system

exhibits longer reaction times

has longer-lasting effects (mins→ days→ weeks)

functions of endocrine system

regulating development, growth + metabolism

maintain homeostasis of blood composition + volume

controlling digestive processes

controlling reproductive activities

what kind of tissue does endocrine gland have

epithelial tissue that makes + releases hormones w/in a connective tissue framework

which are solely endocrine

pituitary, pineal, thyroid, parathyroid, adrenal

places w endocrine cell in clusters in organs

hypothalamus, skin, thymus, heart, liver, stomach, pancreas, small intestine, adipose CT, kidneys +gonads

hormonal stimulation

gland cell releases its hormone when some other hormone binds to it

ex: TSH stimulates thyroid gland

humoral stimulation

gland cell releases its hormone when there is a certain change in levels of nutrient or iron in the blood

ex: release of insulin when rise in glucose

nervous system stimulation

gland cell releases its hormone when a neuron stimulates it

steroids

lipid-soluble from cholesterol

• ex: gonadal (estrogen), adrenal cortex (cortisol),

• calcitriol is really a sterol

• - vitamin D

biogenic amines (monoamines)

catecholamines, TH, melatonin

water-soluble except for TH

• NP + lipid-soluble

proteins

most hormones in this cat.

water-soluble chains of amino acids

local hormones

signaling ‘cules’ that don’t circulate in blood

bind to cells

autocrine stimulation

a cell secretes a signal molecule that binds to receptors on the same cell

paracrine stimulation

cells release signaling molecules (paracrine factors) that travel a short distance and bind to receptors on nearby target cells, altering their behavior

eicosanoids

from fatty acids w/in phospholipid bilayer

• synth. through enzymatic cascade

prostaglandins

stimulate pain + inflammatory responses

aspirin + other non steroidal anti-inflammatory drugs block prostaglandin formation

eicosanoid formation

phospholipase A2 removes arachidonic acid from phospholipid

other enzymes convert arachidonic acid to a subtype of eicosanoid

how do lipid-soluble transport in blood?

NEED A CARRIER PROTEIN

don’t readily dissolve in blood

carriers protect hormones from early destruction

are most hormones bound or unbound

most are bound

unbound (free) hormone

able to exit blood + bind to target cell receptor

how do water-soluble hormones travel?

travel through blood

don’t need a carrier protein

hormone release

positively related

an increase release results in higher blood concentration

ex: high blood sugar increase in insulin release

hormone elimination

enzymatic degradtion in liver cell

removal from blood via kidney excretion or t.cell uptake

faster the elimination rate, lower the blood concetration

half-life

time necessary to reduce a hormone’s concentration to half its original level

what happens to hormones with a short half-life

must be secreted frequently to maintain normal concentration

do water-soluble have a long half life?

no- have a short half-life

lipid-soluble hormones

diffuse across t. cell membrane

receptors in cytosol or nucleus

once hormone cell binds to receptor it forms hormone-receptor complex

Hormone-response element (HRE)

results in transcript of mRNA, which is translated to a protein

• may have structural or metabolic effect

lipid-soluble will only bind to the outside of the cell receptors

Signal transduction pathway

hormone is 1st messenger- intiates events by binding to receptor

binding activates a G-protein (internal membrane protein that binds a guanine nucleotide)

• results in binding of GTP instead of GDP

G-protein activation causes activation of a membrane enzyme like adenylate cyclase or phospholipase C

second messenger- chemical modifies cellular activity

adenylate cyclase activity

after hormone (ex: glucagon) binds to its receptor G protein

activated G protein → adenylate cyclase

adenylate cyclase → cAMP

cAMP activates protein kinase (A)

protein kinase A phosphorylates other ‘cules’

phospholipase C activity

binds to receptor, G protein

activated G protein → phospholipase C

phospholipase C splits PIP₂ into diacylglycerol (DAG) + inositol triphosphate (IP₃)

DAG is a 2nd messenger of the membrane that activates protein kinase C

IP₃ is a 2nd messenger leaves membrane + causes increase in Ca²⁺ in cytosol

• ca²⁺ acts as a 3rd messenger, activating kinases → ion channels

action of water-soluble hormones

activation or inhibition of enzymatic pathways '

growth through cellular division

release of cellular secretions

changes in membrane permeability

muscle contaction or relaxation

Intracellular enzyme cascade

signal amplified at each step

• few hormone ‘cules’ change many ‘cules’ w/in cell

signaling pathway controls

• cells possess mechanisms to quickly inactivate intermediate

  • ex: break down 2nd messengers

how to target cells varies

number of receptors for the hormone

stimulates response to other hormones

up-regulation

increases # of receptors

increases sensitivity to hormone

• sometime when blood levels are low

• sometimes when development, cell cycle, cell activity

down-regulation

decreases # of receptors

decreases sensitivity to hormone

sometime when blood levels are high
sometimes when development, cell cycle, cell activity

ex: diabetes 2

synergistic interactions

one hormone reinforces activity of another hormone

ex: estrogen + progesterone

permissive interactions

one hormone requires activity of another hormone

ex: oxytocin milk ejection effect requires prolactin’s milk generating effect

antagonistic interaction

one hormone opposes activity of another hormone

ex: glucagon increase blood glucose while insulin lowers it

Pituitary gland (hypophysis)

inferior to HT in sella turcica of sphenoid bone

connected to HT by infundibulum

split btw anterior + posterior

posterior pituitary (neurohypophysis)

smaller, neural part of PG

HT neurons project through infundibulum + release hormones in PP

• somas in supraoptic nucleus + paraventricular nucleus

• axons in hypothalmo-hypophyseal tract of infundibulum

• synaptic knob w/in PP

what does supraoptic nucleus produce?

ADH

what does paraventricular nucleus produce?

oxytocin

Hypothalamo-hypophyseal portal system

blood vessels connects HT to anterior pituitary

primary plexus

porous capillary network associated with HT

secondary plexus

capillary network associated with AP

hypophyseal portal veins

drain primary plexus + transport to secondary plexus

What does the posterior pituitary release

storage + release site for antidiuretic hormone ADH and oxytocin OT made in HT by neurosecretory cells

antiduretic hormone (vasopressin)

made in supraoptic nucleus

functions: decreases urine production, stimulate thirst, constrict blood vessels

oxytocin

made in paraventricular nucleus

functions: uterine contraction, milk ejection, emotional bonding

How does the HT and anterior pituitary gland interact?

HT hormonally stimulates anterior pituitary to release its hormones

HT secretes regulatory hormones

• travel via portal blood vessels to pituitary

• anterior pituitary secretes hormones into general circulation

what are the inhibiting hormones?

prolactin-inhibiting (PIH) and growth-inhibiting (GIH)

what are the releasing hormones?

thyrotropin-releasing (TRH), prolactin-releasing (PRH), gonadotropin-releasing (GnRH), corticotropin-releasing (CRH), growth hormone- releasing (GHRH)

thyroid-stimulating hormone (TSH)

thyrotropin

release by TRH from HT

cause release of TH from thyroid gland

TSH→ HT→ TRH→ thyroid gland → TH

protecting (PRL)

release by PRH, inhibited by PIH from HT

causes milk production, mammary gland growth in females

PRH→PRL→ PIH from HT

adrenocorticotropic hormone (ACTH)

corticotropin

release by CRH from HT

causes release of corticosteroids by adrenal cortex '

HT→ CRH→ ACTH→ adrenal cortex → corticosteroids

gonadotropins: follicle-stimulating (FSH) and luteinizing hormone (LH)

release by GnRH from HT

female: regulate ovarian development + secretion of estrogen + progesterone

male: sperm develp’t + secretion of testosterone

growth hormone (GH, somatotropin)

causes liver to secrete insulin-like growth 1 + 2

GH + IGFs function synergistically to stimulate cell growth + division

hypophysectomy

surgical removal of PG bc of tumors

various H’s need to be replaced + their level need to be monitored

where do GHRH + GHIH come from?

the HT

the amount impacts a person’s age, time of day, nutrient level, stress + exercise

effects of GH

stims release of IGFS from liver

all cells have receptors for GH, IGFs or both

• H stimulate increase protein synth., cell division, cell differentiation

glycogenolysis

breakdown of glycogen into glucose

gluconeogenesis

conversion of nutrients to glucose stimulated

glycogenesis

synthesis of glycogen inhibited

lipolysis

breakdown of triglycerides stimulated

lipogenesis

formation of triglycerides inhibited

Pituitary dwarfism (GH deficiency)

littlee= GH production

from HT or pituitary problem

short stature + low blood sugar (hypoglycemia)

pituitary gigantism

too much GH

excessive growth + increased blood sugar

acromegaly

excessive GH in adult

enlargement of bones, face, hands + feet

increase release of glucose + organ increase

from loss of negative feedback

anatomy of thyroid gland

inferior to thyroid cartilage of larynx, anterior to trachea

• midline by isthmus

Follicular cells

cuboidal epithelial cell that surround a central lumen, synthesize thryroglobulin (TGB)

• produce + release TH

Parafollicular cells

cells btw follicles, make calcitonin

• hormone decreases blood Ca levels

Hypthalamic-pituitary-thyroid axis

cold temp, pregnancy, high altitude, hypoglycemia or low TH cause HT to release TRH

TRH → AP→ TSH

TSH binds to follicular cell → release Th

T₃

triiodothyronine

more active

T₄

tetraiodothryronine

more abundant

Effects of TH

increases metabolic rate + protein synthesis in targets

• stims. sodium-potassium pump in neurons

• calorigenic: generates heat, raises temp

• stims. increased amino acid + glucose uptake

• increase # of cellular respiration enzymes w/in mitochondria

what do hepatocytes do?

stim. increase blood glucose

• TH causes increases in glycogenolysis + gluconeogenis, decreased in glycogenesis

what do adipose cells do?

stim. increase blood glycerol + fatty acids

• TH increase in lipolysis + decrease in lipogenesis

  • save glucose for the brain

How does TH affect the heart?

increases heart rate + force contraction

• increased blood flow tp deliver more nutrients + oxygen

• causes heart to increase receptors for epinephrine + norepinephrine

HYPERthyroidism

excessive production of TH

increased metabolic rate, weight loss, hyperactivity, heat intolerance

caused T₄ ingestion, excessive stimulation by pituitary or loss of feedback control in thyroid (Graves disease)

HYPOthyroidism

decreased prod. of TH

low metabolic rate, legsrthy, cold intolerance, weight gain

caused by decrease Iodine intake, loss of pituitary stimulation of thyroid, postsurgival or immune destruction (HASHIMOTO )

goiter

enlargement of thyroid

lack of dietary iodine preventing iodine from producing thyroid hormone

Calcitonin

released from parafollicular cells of thyroid gland

stimulus: high blood Ca++ or stress from exercise

acts to decrease blood Ca++

• inhibiting osteoclast activity

• stimulate kidney to increase excretion of calcium in urine

adrenal medulla

inner core of gland

releases EPI + NOR w sympathetic stimulation

adrenal cortex

has 3 regions + synthesizes more than 25 corticosteroids

mineralocorticoids

regulate electrolyte levels

ZONE GLOMERULOSA: thin, outer layer

• aldosterone fosters Na+ retention + K+ secretion

Glucocorticoids

regulate blood sugar

ZONA FASCICULATA: middle layer

• cortisol increase blood sugar

gonadocorticoids

sex hormones

ZONA RETICULARIS: thin, inner

androgens: sex h’s by adrenal

• made into estrogen

what do cortisol and corticosterone do?

increase nutrient level in blood

• resist stress + repair injured tissue

What is regulated by the hypothalamic-pituitary-adrenal axis

stress, late stages of sleep, low levels of cortisol to release CRH

cortisol travels through blood attached to carrier proteins

• regulated by negative feed back

• cortisol inhibits release of CRH from HT + ACTH from AP

uses of cortisol or corticosterone

inflammation

inhibits inflammatory agents + suppress immune system

high doses: increase risk of infection, cancer, retention of Na + H20, inhibits CT repair

Cushing syndrome

chronic exposire to excessive glucocoticoid H in ppl for corticosteroid therapy

obesity, hypertension, hirsutism (male-pattern hair growth) kidney stones, menstrual irregularities

Addison disease

form of adrenal insufficiency

when adrenal gland fail

weight loss, fatigue + weakness, hypotension + skin darkening