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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…

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