endocrine physiology Flashcards
components of the endocrine system
hormones, organs, metabolites/metabolic products
hormone communication
produced in one area, transported by blood, affect cells in another area, act in low concentration
paracrine communication
produced in one cell, transported in extracellular fluid to adjacent cells, affect those.
some overlap with hormones: prostaglandins, cytokines, somatomedins
neurotransmitters type of communication
paracrine but special
autocrine communication
produced by and affect same cell
2 main classes of hormones
proteins (polypeptides)
steroids
protein hormone synthesis
- pre pro hormone made in ribosome
- ‘pre’ part attaches to RER leaving a prohormone
- pro hormone put into cytoplasmic vesicles and lose ‘pro’
- hormone is stored in coalesced granules until release
- secretion mediated by ATP, Ca2+
steroid hormone synthesis
formed as needed, not stored
mostly made from cholesterol (cholesterol is made in the liver and can be stored)
can be built from scratch from acetate
formed in the mitochondria and other cell components
protein hormone transport
proteins are mostly hydrophilic, simply dissolve in blood
steroid hormone transport
lipophilic
associate with specific binding proteins that are hydrophilic
binding proteins are very specific to the hormone
also non specific binding to albumin for transport
binding and unbinding is in equilibrium (unbound is 1%)
protein hormone receptors
on cell surface
trigger a cascade of activations of enzymes
eventually signal to the nucleus
steroid hormone receptors
in cytosol or nucleus
(steroid can diffuse into cell)
shorter pathway to upregulate the nucleus
degredation of protein hormones
cleaved by peptidases
degredation of steroid hormones
steroid hormones are reduced, conjugated with sulfates or glucuronides.
then they are water soluable and can be excreted in urine
what do hormones do?
regulate metabolism, mineral balance, water balance, energy production and maintenance, reproductive control
most hormones only target one function
negative feedback loop
most feedback is negative, in the sense that an adequate concentration turns off some stimulatory sequence
negative feedback keeps hormonal levels from increasing to abnormal levels
how to pinpoint a failure in a feedback loop
measure the hormone
measure the metabolite
measure any stimulatory hormone
this pinpoints the failure
posterior pituitary
pars nervosa
cell bodies are in the hypothalamus, axons go to posterior pituitary
hormones are released from there
- oxytocin
- vasopressin
posterior pituitary
pars nervosa
cell bodies are in the hypothalamus, axons go to posterior pituitary
hormones are released from there
- oxytocin
- vasopressin
oxytocin
milk letdown
smooth muscle contraction during parturition
maternal behavior and bonding
from posterior pituitary
vasopressin
same as antidiuretic hormone
reclaims water from urine to increase blood volume
constricts arterioles to decrease functional blood volume (increase BP)
moderate behavior effects (maternal behavior and bonding)
absence leads to diabetes insipidus (too much unconcentrated urine)
from posterior pituitary
anterior pituitary
glandular, not nervous
complicated embryonic region (lots of things can go wrong)
several distinct cell types, each a specialist for one hormone
Growth hormone
growth hormone
from ant pituitary
negative feedback from somatomedin
stim growth of bones (length if epiphysis open, width if epiphysis closed)
causes gluconeogenesis (can cause moderate hyperglycemia)
deficiency of growth hormone
dwarfism, complicated with other syndromes with other hormone problems
hypersecretion of growth hormone before maturity
gigantism
hypersecretion of growth hormone after maturity
acromegaly
usually cats
diabetic from exhaustion of beta cells
thyroid stimulating hormone (TSH)
stimulates growth and activity of thyroid follicular cells
from ant pituitary
follicular cells make mostly tetraiodothyronine (T4) and also triiodothyronine (T3)
T4 is placed into colloid into follicular lumen attached to thyroglobulin (high affinity, high specificity)
when needed, it is absorbed, split from the thyroglobulin, and secreted into bloodstream. Lipophilic, so attached to thyroid binding globulin
T3 and T4
follicular cells make mostly tetraiodothyronine (T4) and also triiodothyronine (T3)
T4 is placed into colloid into follicular lumen attached to thyroglobulin (high affinity, high specificity)
when needed, it is absorbed, split from the thyroglobulin, and secreted into bloodstream. Lipophilic, so attached to thyroid binding globulin
T4 is the main product, but metabolized to T3 by kidney and liver. T4 and T3 are both metabolically active
T3 and T4 interact with receptors in the nucleus, NOT on the cell surface
thyroid functions
several actions to increase metabolism
increase O2 uptake and use, enhance heat production
increase glucose absorption from gut, enhance movement of glucose into cells (partly by insulin)
facilitate growth along with growth hormone
enhance lipolysis and can lead to hypercholesterolemia
enhance neural function and cardiac function
overstimulation by TSH
due to iodide deficiency or poisoning of enzymes. T3 and T4 cannot be made
hypersecretion of T3/T4 from hyperplastic region in cats
autonomous secretion, so ↑ T3/T4, ↓TSH (neg feedback)
adrenal glands
2 independent glands:
cortex – comes from mesodermal coelomic epithelium, produces steroid hormones
medulla – comes from neurectoderm, produces vasoactive catecholamines
adrenal glands cortex
comes from mesodermal coelomic epithelium, produces steroid hormones
adrenal gland medulla
comes from neurectoderm, produces vasoactive catecholamines
basic action is similar to a postgangionic sympathetic neuron
release catecholamines into the blood stream instead of into a neuronal synapse
fight or flight
- epinephrine and norepinephrine with a1 a2 b1 b2 b3 receptors
zona glomerulosa
adrenal cortex
mineralocorticoids, not pituitary dependent
zona fasciculata
adrenal cortex
glucocorticoids, pituitary dependent (ACTH)
zona reticularis
adrenal cortex
glucocorticoids and sex steroids, pituitary dependent
temporary fetal zone in adrenal cortex
helps with estrogen production during pregnancy and soon after parturition. regresses postpartum
steroid hormones
all inter-related
production depends on specific enzymes that are localized to specific cells
some overlap of function
glucocorticoids (transport, function, examples)
transported with proteins in blood, both specifically and nonspecifically
- bind to receptors in cytosol, then go to nucleus and affect transcription
function:
- metabolic: gluconeogenesis, lipolysis, protein catabolism, increased water excretion
- inflammatory: decreased in general, suppressed immunity
Examples:
- cortisol is mainly metabolic
- corticosterone is mainly anti-inflammatory
they each overlap, and also overlap with mineralocorticoids
highest in day, lowest at night
synthetic mimics are common as therapeutic drugs, mainly for anti-inflammatory properties
glucocorticoid ACTH feedback
stress upregulates ACTH secretion
ACTH stimulates production of glucocorticoids
glucocorticoids inhibit ACTH secretion
chronic stress is a major stimulation
using glucocorticoids as clinical therapeutics
main use is anti-inflammatory
pathways to upregulate or downregulate are slow and delicate
exogenous products work quickly
once removed the body responds slowly
taper exogenous sources slowly to allow endogenous system to recover
mineralocorticoids
aldosterone is the main one
affects distal renal tubules, also salivary glands, sweat glands.
moves Na+ from cell to interstitium, water follows
this also loses K+ , H+ so can cause metabolic alkalosis
aldosterone production
renin is an enzyme from kidney, upregulated by ↓ blood pressure
renin activates angiotensinogen to angiotensin I which goes to angiotensin II
angiotensin II stimulates aldosterone production
mineral balance
many factors interact
electrolytes are essential for fluid homeostasis as well as cell functions
control mechanisms (angiotensin/renin/aldosterone system) in heart failure
↓ heart function
↓ blood pressure (this is all the renin-angiotensin-aldosterone system actually sees and responds to)
↑ renin ↑ angiotensin II ↑ aldosterone
↑ fluid retention, further overloading heart which cannot raise blood pressure, further stimulating renin
epinephrine/norepinephrine
from adrenal medulla, fight or flight
shunt blood from viscera to muscle
raise blood glucose
increase heart rate and stroke volume
considerable overlap between function and receptors
pancreatic islets
endocrine pancreas
⍺ cells - glucagon
β cells - insulin
D cells - somatostatin
F cells –pancreatic polypeptide
pancreatic islets
endocrine pancreas
⍺ cells - glucagon
β cells - insulin
D cells - somatostatin
F cells –pancreatic polypeptide
insulin
highly conserved sequence across all species
from pancreatic β cells
it is essential for moving glucose, fatty acids, and amino acids from the blood into cells (liver) where they are transformed into their storage forms:
- glycogen
- triglycerides
- proteins
mostly released in response to high blood glucose
interacts with a host of other hormones as well
this provides for fairly tight control over BG levels
glucogon
most from pancreas ⍺ cells, also from intestinal cells
decreases glycogen synthesis
increases glycogenolysis
increases gluconeogenesis
therefore – raises blood glucose
somatostatin
pancreatic D cells
many different sites of production
inhibits secretion of other islet hormones
diminishes gut motility
pancreatic polypeptide
pancreatic D cells, islets are the only source
increases gut motility
gastrointestinal hormones
from isolated cells in the gastrointestinal mucosa
not a localized site
many different hormones with slightly different effects
calcium homeostasis
Ca2+ is a very important ion.
Functions
- cell membranes
- muscle contractility.
It MUST be maintained within a narrow range… or you die.
Hypocalcemia is more immediately threatening than hypercalcemia
three main players:
- parathormone
- calcitonin
- vitamin D
parathormone
from the parathyroid
secreted:
- in response to low [Ca2+]
- in a diurnal rhythm, highest right after waking.
resorbs Ca2+ from bone
increases resorption in kidney
decreases renal resorption of PO4-
upregulates activation of vitamin D
calcitonin
from the parafollicular cells (also called C-cells) of the thyroid.
lowers [Ca2+], thereby increasing [P04-]
[Ca2+] and [P04-] exist in inorganic chemistry equilibrium. the product is usually about 40, with [Ca2+] 10 and [P04-] 4.
at a product level of 70, Ca2P04 simply precipitates out
vitamin D
functions as a hormone
produced in skin, ultraviolet light essential for synthesis
inactive form goes to active form by sequential steps in liver and kidney
enhances absorption of Ca2+ from intestine.
high [P04-] induces a pathway that leads to inactive vit D
