Hormones
Chemical messengers
Hormones can only elicit a response in cells
That have an appropriate receptor for that hromone
Three different classes of hormones
Biogenic amines
Protein/peptide hormones
<100 amino acids
Peptide hormones
>100 amino acids
Protein hormones
Biogenic amines
Epinephrine
Rough Endoplasmic reticulum
Produces pre-hormones
Pre-hormones are cleaved into pro-hormones in the
Golgi apparatus for packaging and further refinement
Prohormones cleaved into active hormones by enymes in the
golgi apparatus or secretory vesicle
Steroid hormones cannot be stored and must be produced on demand because
They can pass through the cell membrane
Steroids are derived from
cholesterol
Steroids are stored within lipid droplets in the cytoplasm
and can be rapidly produced when needed
Steroid hormones cannot be stored and must be produced
on demand
Progesterone, DHEA, androgesterdione
stimulated by ACTH in adrenal cortex, causing cleavage enzyme to break cholesterol into hormones
Aldosterone synthase
final enzyme that converts corticosterone to aldosterone
16 a hydroxygenase
important for converting corticosterone to cortisol
21a hydroxylase
important enzyme
cells have receptors for hormones that act as
a molecular trigger that turns specific functions on or off
Response of target cells can include
opening or closing ion channels
Synthesis of enymes or
proteins
Acctivation ro deactivation
secretion of a cellular
product
Stimulation of mitosis
Degree of response is not just determined by presence of receptor but also by
Concerntration of hormone,
Number of receptors
Affinity of
hormone to the receptor
presence or absence of
Hormone
Sender
Receptor
sites that can trigger response
Upregulation
Increase cell receptors
Downregulation
Decrease receptors
Synergistic hormones
Work together to produce response that may be additive or complementary
Additive effect
2+2+2 = 7 effect
examples of additive hormones
Glucose, epinephrine, cortisol.
All 3 of these together get large dynamic increase in glucose
Complementary
means each hormone produces a different response that is part of a bigger complete picture. Coorperative effects of hirmones required to achieve desired end state
Cortisol
Adrenal glands release during distress during sickness to help you deal with distress
Permissive effect
A hormone enhances the responsiveness of the target cecll to a second hormone or increases the activity of the second hormone
Antagonistic hormones
Have opposing effects on the same tissue
Oxytocin and prolactin
Baby suckles, stimulates oxytocin, oxytocin causes uterine contraction and milk release.
Estrogen stimulates progesterone in endometreum
Endometrial lining increases response to endometrium and increases chances of implantation
Insulin and glucagon
Antagonistic hormones
Somatostain opposes both insulin and glucagon
Helps to maintain normal range
Hormone receptor interactions
How cell communicates with that hormone
Water soluble
Can travel easily in plasma, cannot get across cell membrane easile
Lipid soluble
Easily makes it across cell membrane, struggles in cytoplasm without carrier protien
Lipid soluble hormones have receptors
within cytoplasm or nucleus of target cell that activates genes and protein synthesis directly
Amino acid based hormones are water soluble and have target receptors on
Cell membranes
Amino acid based hormones are usually working with
second messengers
Common second receptors for hormone receptors are
Cyclic AMP (cAMP)
Inositol triphosphate
(IP3)
Diacylglycerol (DAG)
Most common signaling pathways are
cAMP and PIP2-Calcium pathways
cAMP signaling pathways involve 3 components of plasma membrane that trigger intracellular cascade
Hormone receptor
G protein
Adenylate cyclase
Hormone binds to receptor
first membrane
Receptor activates g protein and the hormone travels inside cell membrane and binds to adenylate cyclase
adenylate cyclase converts ATP into cAMP and tow inorganic phosphates cAMP=second messenger
Protein kinases are enzymes that phosphorylate proteins(enzymes)
triggers cascade of chemical reactions within cell
PIP2 calcium mechanism
uses GPCR
Activation of Gprotein splits phospholipid into two 2nd messenger
IP3 7 DAG
Like cAMP, DAg activates protein kinase which triggers cascade of reactions
inside the cell
some receptors use cGMP instead of cAMP
still work similaryl
insulin and IGF-1 use
tyosine kinase instead of cAMP
Receptor is an enzyme called
Tyrosine-kinase
Bindinger causes dimerization and autophosphorylation of the receptor which triggers
traslocation of GLUT4
Steroid hormones in serum
attach to carrier proteins because they are insoluble
on arrival at target cell, hormone deteaches from carrier protein
binds to receptor inside the ccell
once inside steroid binds to receptor inside cell and binds to DNA
Thyroxine
Bind of the complex to the DNA initiates transcription of gene with mRNA
...
need to know second messengers wrk with Gprotein
moving a enyme to allow for message to make it into cell
level in blood reflects
how much it is being secreted
hormones shouldnt accumulate in blood because they are used by target cells and
turned off by negative feedback
half lives for hormones can be
minutes to days
effects of a hormone on target cells are dependent on concentration of hormone and
receptors
secretion of the hormone is triggered by a stimulus after which the plasma levels of the hormone increases
secretion is inhibited by cell change or release of product by target cell. This is negative feedback
endocrine cell, target cell, response
simple negative feedback.
Ca low
PTH increases, liberates
ca from bone
ca increases, PTH is turned off
complex negative feedback (most common)
releasing hormone
target gland
Stimulating
hormone
Target tissue
secretion by 3 mechanisms
Humoral
neural
Hormonal
Humoral refers to
blood
Glucose, Ca, Na, K
Hormonal control
Most common via releasing hormones via hypthalamic pituitary axis (HPA), and pituitary tropic hormones
tropic means
stimulates another gland to release its hormones
Neural control involes
neuro-endocrine interface
epinephrine would be an example of
neural control
parasympathetic
lots of GI effects
sympathetic
inhibits GI system
HPA
Hypothalamic pituitary axis
HPA REALLY REALLY REALLY
IMPORTANT
HPA typically 3 hormone sequence
Hypothalamus detects stimulus and
secretes a releasing hormone
1
Releasing hormone stimulates anterior pituitary to release a
tropic hormone 2
Tropic hormone stimulates target gland which
releases a stimulating hormone 3
Thyroid hormone increase
basal metabolic rate and heat production
thyroid hormone regulates
growth and development of tissues
Thyroid hormone
has permissive effects on the action of epi and norepi by upregulating beta reeptors in heart and nervous system
thyroid hormone is actually how many hormones
two, T3 and T4
Most T3 is T4 that is
converted in tissue
Thyroxine aka
T4
Colloid contains
Thyroglobulin
TG
Thyroglobulin
Iodide trapping is the first step in
Thyroid hormone synthesis
Iiodine is co-transported with Na+ into the follicular cells
where it is transported into the colloid by a membrane protein called pendrin
Iodide is oxidized to become I2
then attached to tyrosine
Tyrosine with one iodine is called
Monoiodotyrosine (MIT)
Diodotyrosine aka
DIT
Next the phenolic ring of MIT or DIT is removed from its tyrosine and added to another DIT to produce either
T3 or T4
To secrete thyroid hormone, follicular cells use endocytosis to engulf colloid where T3 and T4 get transported out of the cell
by thyroid binding globulin TBG
TBG vs TG
big deal
When TSH stimulated
secretory granules get really big and produce a lot more colloid
secretory granules are
normally slowly moving a little bit of colloid continuously
Dont care about knowing chemical structures
or isomers
Hypothalamus stimulated by cold temperatures, decreased thyroid hormone or other factors
TRH stimulates release of TSH
q
Adrenal glands play an important role in response to stress
Stress is anything physiologic or psychologic
The hypothalamus activates sympathetic nerves
stimulates adrenal medulla to secrete epi/norepi
If a threat persists for more than 10 mins or so
CRH will be released from hypothalamus which will stimulate ACTH
ACTH will stimulate
adrenal cortex to release cortisol
Cortisol elevates blood sugar by stimulating
gluconeogensis in liver and glucagon secretion from pancreas
Cortisol also stimulates lipolysis in adipose tissue
releasing fatty acids into circulation that can be used to make energy
Takes 20-30 minutes
for the body to recover from stressor
General adaptation syndrome 3 stages
Alarm stage Hypothalamic pituitary adrenal axis
Reistance:
parasympathetic response cortisol and glucose are still
evelated
Exhaustion: immune supression overall deterioration
cortisol is major negative feedback molecule
by telling hypothalamus to knock it off
female Gonadotropins
GnRH to pituitary
LH
FSH to ovaries
(inhibin and estrogen negative feedback on pituitary)
male gonadotropin
GnRH to pituitary
Pituitary to testes
LH
FSH
(inhibin negative feedback on pituitary) (testosterone negative
feedback on hypothalamus)
Growth hormone
Growth hormone releasing hormone to pituitary
Pituitary growth
hormone to liver cells
Liver cells IGF I negative feedback to pituitary and hypothalamus
Prolactin
Breast development and synthesis of milk
Negatively regulated by dopamine
Vasopressin (ADH)
Peptide hormone, synthesized in hypothalamus, stored in posterior pituitary
ADH triggers
sense of thirst
ADH increase
number of water channels in renal collecting tubules/ducts called aquaporins
aquaporins increase
water reabsorption
high osmolarity increases
ADH production
Volume always takes precedence
compared to osmolality
Paracrine and autocrine regulation are more
localized
Paracrine and autocrine are technically
not part of the endocrine system
Paracrine affect
cells next door
Autocrine affect
its own cell, or cell of same exact type nearby
cytokines, interleukins, interferons, tumor necrosis factor
...
endothelium produces nitric oxide and bradykinin which stimulate
relaxation of vascular smooth muscle
endothelin promotes
vasoconstriction
eicosanoids
function mostly by system, mostly looking at prostaglandins
prostaglandins give you
fever