Transcript 11aendocrine

Chapter 11
Hormones
Lecture map
Hormones:
- general biochemistry
- endocrine organs and effects
- anterior pituitary
- hypothalamus
- posterior pituitary
- adrenal cortex
- adrenal medulla
Lecture map
Next:
-endocrine organs and effects
- thyroid
- parathyroid
- pancreas
- pineal
- thymus
- placenta, gonads
- adipose, skin, kidneys, heart, GI tract
- autocrine system
- endocrine signal transduction
HORMONES
Hormones
Endocrine: into blood
Exocrine: ducts
Autocrine: same organ, same tissue
Paracrine: same organ, different tissue
Endocrine hormones
Endocrine hormones are in blood, so
they reach all cells of the body.
Each hormone only affects SOME cell
types and tissues.
- the cell has to express the particular
receptor to “hear” the hormone signal.
Endocrine hormones
Secretion
hormone
receptor
Target cell
Hormone types
Polar:
Most hormones.
Bind to receptor protein on pm.
Lipophilic (nonpolar):
Cross pm, act inside target cells.
Steroid hormones and thyroid hormones.
Can take orally, as pills.
Hormone types
Hormones:
Often amino acid derivatives or peptides.
Steroid hormones are made from
cholesterol.
Receptors
Hormone receptors on target cells:
Very specific
Often high affinity (bond strongly)
Integral mb proteins.
Effect of hormones
Effect of hormone depends on…
- blood levels
- number of receptors on target cells
- affinity of receptors for hormones
Effect of hormones
Blood levels depend on:
- gene expression
- half-life of hormone
- for lipophilic hormones: how much is bound
to protein carriers
Regulation
Endocrine hormones: secreted into blood, then
removed by target organs and liver, converted
to inactive form, and excreted.
Half-life:
Is general term for time required for the [molecule] to
be reduced to half of reference level.
This lecture: blood [hormone].
Way to quantify permanence of hormone.
Minutes to hours, even days.
Regulation of receptor
Upregulation:
High or constant hormone levels can lead to
more receptor proteins on target cells
(usually through gene expression) and a
greater response by the target cell.
Regulation of receptor
Downregulation (desensitization):
Prolonged, continuous exposure to high [hormone]
can lead to diminished response (to same amount
of hormone).
One way: decrease in number of receptors on target
cells.
Through endocytosis, lysosomes, protein degradation.
Pulsatile secretion of hormone (in spurts, over time)
may prevent downregulation of receptor.
Regulation of hormone
Hormone regulation:
Active form= a certain configuration.
Often inactive in blood.
Regulation of hormone
Prohormone/prehormone: precursor
molecule, usually inactive and can be
modified (often cut) to become active.
Preprohormone: precursor to
prohormone!
Hormone effects
Physiological range: [hormone] which produces
normal responses.
[pharmacological] are usually higher, can have
different effects from physiological range.
Side effects of drugs
Pharmacological drugs have side effects
because:
Hormones, neurotransmitters, etc., regulate many
targets, in many parts of the body.
High doses may cause binding to other receptors (less
specificity).
Hormonal Interactions
Synergistic: enhance each other’s action.
“two is better than one plus one!”
Permissive: permits action of another
hormone.
Antagonistic: act in opposition; important for
homeostasis!
PITUITARY GLAND
Pituitary Gland
In diencephalon.
Anterior lobe.
Posterior lobe.
Anterior pituitary
Anterior pituitary
Derived from epithelial tissue.
Controls growth of many other endocrine glands (“master
gland”)
- each known as an axis
Trophic effects:
High blood [hormone] causes target organ to
hypertrophy.
Low blood [hormone] causes target organ to atrophy.
Anterior pituitary
Growth hormone (GH) -> many tissues, grow!
Thyroid-stimulating hormone (TSH) -> thyroid secretes
T3, T4
ACTH -> adrenal cortex to secrete glucocorticoids
Prolactin -> milk
Gonadotrophic hormones:
FSH -> ovarian follicles, sperm cells
LH -> ovulation; testosterone
Anterior Pituitary
Hypothalamus
Hypothalamus regulates the anterior
pituitary!
Physically linked, blood portal system.
Hypothalamic hormones often called
“(something) releasing hormones”
Hypothalamus
Hypothalamus
Hypothalamic hormones -> Anterior pituitary hormones
GHRH increases GH
Somatostatin inhibits GH
TRH increases TSH
CRH increases ACTH
PIH inhibits prolactin
GnRH increases FSH and LH
Regulation of Anterior Pituitary
Mostly through negative feedback
inhibition from target organs to
hypothalamus or directly to anterior
pituitary.
Ex: TSH -> T4 ---l TSH
Regulation of Anterior Pituitary
So, once a certain amount of hormones
are made, they shut off the system
producing them!
Antagonistic effectors
GHRH -> GH l- Somatostatin
Somatostatin -l GH
TRH -> TSH -> T4
T4 -l TSH, TRH
CRH -> ACTH -> Glucocorticoids
Glucocorticoids -l CRH
PRH -> Prolactin
PIH -l Prolactin
Antagonistic effectors
GnRH -> FSH, LH
Gonadal hormones -l FSH, LH
Estogen can inhibit, or stimulate,
depending on levels!
Some levels even stimulate synthesis of
FSH, LH, but prevent release. (p. 932)
Testosterone -l GnRH, FSH, LH
Hormones
Estrogens are a family of several hormones.
(Testosterone is one hormone.)
Male brains have an enzyme that turns testosterone
into estrogens!
(note: PIH is dopamine!)
Hormones
GH:
- “fountain of youth?!?”
- secreted mostly in adolescence
- too much: gigantism, acromegaly
- too little: pituitary dwarfism
- stimulates uptake of amino acids into cells
Hormones
Note:
stress -> CRH -> ACTH -> glucocorticoids
Posterior pituitary
Posterior pituitary
Formed by downgrowth of the brain during
fetal development.
Under direct neural control.
Nerve fibers extend through the
infundibulum.
Posterior pituitary
Posterior pituitary
Stores and releases 2 hormones that are
produced in the hypothalamus:
- Antidiuretic hormone (ADH)
- Oxytocin
Posterior pituitary
Antidiuretic hormone (ADH):
- aka vasopressin
- promotes the retention of H20 by
the kidneys
Posterior pituitary
Oxytocin:
- stimulates contractions of the uterus
during parturition.
- stimulates contractions of the mammary
gland alveoli for milk-ejection reflex.
- bonding with baby?!
- orgasm?
Posterior Pituitary
ADRENAL GLANDS
Adrenal Glands
Paired
organs that
cap the
kidneys.
Each: outer
cortex and
inner
medulla.
Adrenal cortex
Adrenal cortex:
- stimulated by ACTH.
- secretes corticosteroids
- different regions secrete different hormones.
- all made from cholesterol.
Adrenal Cortex
Corticosteroids include:
- mineralocorticoids:
- glucocorticoids
- gonadocorticoids
Adrenal Cortex
Mineralocorticoids:
- aldosterone
- targets kidneys
- affects Na+ and K+ balance
- stimulates transcription of Na+/K+ ATPase pump!
- more aldosterone -> more Na+, water in body
- stress -> CRH -> ACTH -> aldosterone -> retain
fluid -> high blood pressure!
Adrenal Cortex
Glucocorticoids (gc)
- cortisol (aka hydrocortisone)
- metabolism, more glucose in blood
- stress -> large increase in gc
- pharmacologically: suppress inflammation, asthma,
rheumatoid arthitis
Adrenal Cortex
Gonadocorticoids:
- aka sex steroids
- include DHEA (precursor for estrogen, testosterone)
- not well understood
http://www.quackwatch.org/01QuackeryRelatedTopics/dhea.html
Adrenal Cortex
Adrenal Medulla
Adrenal medulla:
Derived from embryonic neural crest
ectoderm (same tissue that produces the
sympathetic ganglia).
Controlled by preganglionic sympathetic
innervation
(is like a postganglionic neuron!)
Secretes adrenaline (aka epenephrine)
(also secretes norepenephrine)
Sympathetic response
Adrenaline:
part of sympathetic response to a threat!
“fight or flight”
Also, fear, sex
Also: tend and befriend
Triggered by physical and emotional/psychological
stress: body responds similarly to “bear in woods”
or to stressful words.
Sympathetic response
Sympathetic response:
Body changes to short-term, muscular focus.
Increased respiratory rate, heart rate, blood
glucose.
Decreased digestion, immune system,
memory, analytical thinking.
Sympathetic response
Adrenaline:
- used medically to stimulate heart or to
dilate bronchioles (in an asthma attack)
when locally administered through an
inhaler
Chronic stress
Chronic stress:
Chronic activation of sympathetic response.
Harder to turn off the sympathetic response,
Cardiovascular damage, attentuated immune
defenses…
Why zebras don’t get ulcers. Robert M.
Sapolsky
Parasympathetic
Parasympathetic response:
Turn on by
- deep breaths…
- “count to ten!” or do a math problem…
- meditate, yoga…