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Transcript
Chapter 17
The endocrine system
overview
hypothalamus – pituitary
other glands
hormone actions
stress
4 ways for cells to communicate
gaps – neurotransmission – paracrine – hormones
endocrine (blood) vs exocrine (ducts, extracellular)
endocrine = intracellular – fenestrated capillaries – seconds to
days for a response – affect may last for days or longer
– persistent with no accommodation
– narrow or widespread affects – chemical communication
– some both endocrine and neuroendocrine
hypothalamus and pituitary
hypothalamus regulates anterior pituitary - by secreting
releasing factors - which enter primary capillaries - which travel
down venules - and diffuse out of the secondary capillaries –
and are picked up by specific pituitary cells
– ant pit derived from cells from pharynx
posterior pituitary (neurohypophysis) hormones are made in
hypothalamic neurons - move down nerve fibers - and are
stored in nerve endings in the posterior pituitary - until nerve
signal from hypothalamus - trigger release from posterior
pituitary – post pit derived from nervous tissue (brain cells)
anterior pituitary hormones
FSH - follicle stimulating hormone, ovary, estrogen, follicle,
testis, sperm production
LH - luteinizing hormone, ovulation, corpus lutein makes
progesterone, testis makes testosterone
TSH – thyroid stimulating hormone, T3, T4, many functions on
metabolism, growth, repair,
ACTH – adrenocorticotropic hormone, glucocorticoids(cortisol)
stress, metabolism,
PRL – prolactin, stimulates milk secretion after birth
GH – growth hormone, most numerous of AP cells (1000X),
mitosis, cell differentiation, growth, repair,
metabolism, (hypothalamic pituitary thyroid axis)
posterior Pituitary Hormones
ADH - anti diuretic hormone, water retention, urine ,
prevents dehydration, also acts as a neurotransmitter
called AVP or arginine vasopressin which constricts
blood vessels at pathological levels
oxytocin - ↑in both sexes during sexual arousal and orgasm,
results in emotional bonding, labor contractions↑, milk
flow↑, bonding to newborn↑
control of pituitary secretions
info coming into brain - integrated and non integrated info to
hypothalamus – hypothalamus has centers for stretch
receptors of blood vessels and heart, suckling, osmoreceptors,
temperature, stress, blood volume, and more
this information is used to regulate and
modulate many involuntary functions
by stimulation and feedback both
positive and negative
growth hormone - widespread effects on
cartilage, bone, muscle, fat, protein, sugars,
metabolism, repair, growth, electrolytes
IGF1 (insulin like growth factor 1),
IGF2, and somatomedins
IGF-1 is a primary mediator of the effects of growth
hormone(GH). Growth hormone is made in the anterior
pituitary gland, is released into the blood stream, and then
stimulates the liver to produce IGF-1. IGF-1 then stimulates
systemic body growth, and has growth-promoting effects on
almost every cell in the body, especially skeletal muscle,
cartilage, bone, liver, kidney, nerves, skin, hematopoietic cell,
and lungs. In addition to the insulin-like effects, IGF-1 can also
regulate cell growth and development, especially in nerve cells,
as well as cellular DNA synthesis.
Somatomedins are produced, predominantly by the liver, when growth
hormones act on target tissue. Somatomedins inhibit the release of growth
hormones by acting directly on anterior pituitary and by stimulating the
secretion of somatostatin from the hypothalamus.
Somatomedins are a group of hormones that promote cell growth and
division in response to stimulation by growth hormone (GH) also known as
somatotropin (STH).
Somatomedins have similar biological effects to somatotropin.
In addition to their actions that stimulate growth, somatomedins also
stimulate production of somatostatin, which suppresses growth hormone
release. Thus, levels of somatomedins are controlled via negative feedback
through the intermediates of somatostatin and growth hormone.
Somatomedins are produced in many tissues and have autocrine and
paracrine actions in addition to their endocrine action. The liver is thought
to be the predominant source of circulating somatomedins.
IGFs have a half life of almost a full day and produce most of
the functions associated with growth hormone
proteins - boosts translation and transcription, stimulates
anabolism and inhibits catabolism
lipids - stimulates catabolism, protein sparing
sugars - glucose sparing, gluconeogenesis by liver
electrolytes - Na↑, K↑, Cl↑, Ca absorption↑
sleep - GH↑ 2X or more after 2 hours of sleep, 90 minute cycle
of release, trauma and stress cause GH↑,
hypoglycemia ↑, high protein meals GH↑, high
carbohydrate meals GH↓,
GH levels = 20 ngm/ml sleep, 30 exercise, 6 adolescence,
1.5 at 65, half life up to 20 minutes
pineal gland
at roof of 3rd ventricle – large and active in children 1 – 5,
secretions decline greatly after puberty, involved with circadian
rhythms, serotonin converted into melatonin (sleep),
secretions fluctuate with light cycles and seasons,
regulates breeding and fertility cycles in lower vertebrates and
probably in mammals,
pineal pathology = precocious puberty,
3rd eye to neuroendocrine transducer
the thymus
endocrine, lymphatic, & immune system
large in fetus, grows until 5 – 6 years old,
shrinks from childhood to adult and then again in 60+ years
T cell production, thymopoietin, thymosin, thymulin
stimulates development of other lymphatic organs
the thyroid gland
largest purely endocrine gland in adults
very vascular, high metabolic rate
TRF – TSH – follicles + lumen + colloid – T4 thyroxine 90% –
T3 triiodothyronine 10%
oxygen use ↑, heat production↑, calorigenic effect,
respiration↑, heart rate↑, heart strength of beat↑,
appetite↑, alertness↑, reflexes↑, GH secretion↑, growth↑,
CHO, lipid, protein catabolism↑,
thyroid has non T4 and T3 cells called
C cells (parafollicular cells)
as Ca↑ - calcitonin secreted – which inhibits parathyroid
glands and osteoblast activity
important in children not in adults unless pathological
parathyroid Glands
4 nodules on the posterior surface of the thyroid
secretes PTH parathyroid hormone
as a response to lower calcium levels
1% drop in calcium = 100% increase in PTH
PTH - osteoclasts↑( Ca & PO4 ↑ in BV) - kidney reabsorbs
calcium - calcitriol↑ - collagen synthesis decreases
adrenal glands – suprarenals
large in newborns and shrinks by 50% by age of 5
cortex 80-90%
medulla 10-20%(sym)
affects minerals, sugars, electrolytes,
immunity, stress, reflexes, energy, healing
adrenal medulla – endocrine & sympathetic ganglion
- preganglion nf - chromaffin cells(post ganglion nf)
- has no dendrites and no axons
- releases products to blood vessels (neuroendocrine function)
- chromaffins release catecholamines (75% epinepherine, 25%
norepinephrine, trace of dopamine
- prepares body for physical action, alertness↑, glucose
sparing, fatty acid catabolism↑, lactate metabolism↑,
insulin↓, heart rate and strength↑, digestion & urine↓,
metabolism↑, glycogenolysis↑, gluconeogenesis↑
adrenal cortex - 25+ corticosteroids from cholesterol
5 important steroids as mineral, gluco and sex steroids
zona glomerulosa = mineralocorticoids
zona fasciculate = spongiocytes, glucocorticoids, androgens
zona reticularis = glucocorticoids and androgens
aldosterone – kidney – Na in↑, K out↑, H2O in↑
cortisol – hydrocortisone – fat & protein catabolism↑,
gluconeogenesis↑, anti inflamitory
androgens – DHEA becomes testosterone & dihydrotestosterone,
male fetus↑, in puberty pubic & axillary hair & scent
glands, libido↑, skeleton growth↑
estradiol – promotes skeletal growth & adult bone mass & secondary sex
characters, menstrual cycle, pregnancy, & lactation
estrogen – only source past menopause,
the pancreas – exocrine & endocrine
1 – 2 million islets of Lamgherhans
20% alpha cells, 70% beta, 5% delta
alpha cells = glucagon, glucose release, fat catabolism, AA reabsorb
beta cells = insulin, absorb all nutrients, glycogen, fat, AA↑, brain,
liver, kidneys, & RBC use glucose without need for insulin,
delta cells = somatostatin, GH inhibition, stomach acid inhibition
PP & G cells = unknown functions
the gonads – exocrine and endocrine
produce hormones, eggs, and sperm
ovaries = estradiol, progesterone, inhibin
theca cells = of follicle, androgens then converted to estrogens
corpus luteum = progesterone
testis = seminiferous tubules make testosterone,
sertoli cells = inhibin decreases FSH which reduces sperm
interstitial cells = testosterone & other steroids
other endocrines
skin = cholesterol –liver to cholecaciferol - kidney to calcitriol
liver = IGF, hepcidin(iron), erythropoietin[EPO](15%),
angiotensinogen(BP),
kidneys = calcitriol(D3), renin(RAA, BV constriction), EPO(85%)
heart = natriuretic peptides, Na out↑, urine vol↑, BP↓
adipose = leptin↓ appetite↑, leptin↑ appetite↓,affects
hypothalamus and active during onset of puberty
osseous = osteoblasts – osteocalcin – beta cells #↑, insulin↑,
inhibits weight gain and development of type 2 diabetes
placenta = estrogen, progesterone, and more during fetal
development, and mammary growth during pregnancy
stomach/small & large intestines = enteroendocrine cells
– more than 10 hormones
– cholecystokinin (CCK) – release of bile in response to fat in
food – anti appeite affect on brain
– gastrin from stomach + food = HCl secretion
– ghrelin from stomach + empty stomach = hunger
– peptide YY(PPY) from small & large intestine signals fullness
hormone chemistry
steroids, monoamines, peptides, protein bound
steroids - from cholesterol (sex steroids, hydrophobic)
monoamines – epi, norepi, dopamine, melatonin, T4, T3
peptides-oxytocin,ADH(9AA), many 92AA base+variable beta chain
synthesis – 4 ring steroid backbone + different functional groups
peptides in active and inactive form, monoamines from
tryptophan & others from tyrosine
transport – made, released to blood, bound(long lasting) or free
receptors – target receptors are proteins or glycoproteins, specific
and saturation - - steroids and T4 and T3 pass into cell and
initiate 2nd messengers - - cAMP, IP3, diacylglycerol(DAG)
initiate cytoplasmic transduction leading to metabolic events
amplification - cascade effect, 1-100-10000-1000000,
cell sensitivity - up or down with regulation=more or less receptors
hormone interactions
synergistic (2 + 2 = 8)
permissive (increases response speed or magnitude of a 2nd)
antagonistic (inhibits speed or magnitude of a 2nd)
clearance – broken down when not needed, usually by liver
or kidney or local enzymes at target cell
metabolic clearance rate = half life rate of destruction
stress and adaptation
stress is anything which upsets homeostasis and
threatens physical or emotional well being
can be excess happiness, sadness, grief, despair, etc.
stress response (general adaptive syndrome) involves epi and
norepi leading to an alarm reaction, resistance to fatigue and
homeostatic exhaustion possibly death
alarm = norepi from sym & epi from adrenal medulla=flight or flight
glycogen catabolism,angiotensin,aldosterone,BP,Na in,H2O in, all↑
resistance = glucose gone, need for alternate fuels, cortisol↑, fat &
protein catabolism↑, gluconeogenesis↑, glucose sparing, long
term = immunity↓, healing↓, sex hormones↓, body running down
exhaustion = no more fat and glycogen, no body chemicals for fuel,
only protein left, now in pathology, H2O in, BP, Na in, K out, all ↑,
body going into hypokalemia and alkalosis causing nerve and
muscle pathology
eicosanoids (paracrine signaling)
- stimulates nearby cells or same cells
- histamines releas by mast cells next to BV & act on BV muscles
- nitrous oxide released by BV cells and act on BV cells- vasodilator
- catecholamines from adrenal medulla diffuse onto adrenal cortex
derived from PUFA (poly unsaturated fatty acid) arachidonic acid
cyclooxygenases convert acid to 3 eicosanoids
prostacyclins - BV cells, inhibits blood clotting & vasoconstriction
thromboxanes-from platelets, stimulate vasoconstriction & clotting
prostaglandins – many kinds, affect smooth muscle, inflammation, plus
reproduction, kidneys, respiration, GI, NS, endocrines
anti inflammatory drugs – inhibit production of eicosanoids
SAIDS – steroidal anti inflammatory drugs
NSAIDS – non steroidal anti inflammatory drugs
COX inhibitors – new class of medicines, new ones arriving
each year – stop the conversion of arachidonic acid to
eicosanoids – many side effects
aspirin does many things – inhibits prostaglandin and
thromboxane synthesis