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Medicine
Endocrinology
Adrenal system
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Terms in this set (68)
_________________ is the central relay station that senses disturbances to homeostasis and integrates appropriate responses
Hypothalamus
________________ relays hypothalamic signals to peripheral and central (i.e. brain) targets.
Pituitary gland
Signaling from hypothalamus to ANTERIOR pituitary occurs (neuronally/ neuroendocrinologically)
Neuroendocrinologically
Signaling from hypothalamus to POSTERIOR pituitary occurs (neuronally/ neuroendocrinologically)
Neuronally
(short/ Long) of negative feedback is the loop that largely regulates hormonal balance.
LONG
Negative feedback signaling occurs at the level of ______________ and _______________(which regions of brain)
hypothalamus + anterior pituitary
Explain the negative feedback mechanism when there's high level of Testosterone:
Testosterone will travel via blood stream to reach Anterior pituitary & Hypothalamus → testosterone level sensed as being too high→ shut down production of factors that stimulate release of testosterone
Classic example of positive feedback mechanism is when there's high level of ______________ hormone in females.
Estradiol
(Estradiol stimulates hypothalamus and anterior pituitary to secrete MORE tropic factors to ovary to stimulate more output of Estradiol)
3 hormones involved in circadian pattern of secretion during SLEEP:
-Prolactin
-Growth hormone
-ACTH
What time of the day is ACTH level the highest ?
Later phase of SLEEP just before waking
What time of the day is Growth hormone level the highest ?
Early phase of SLEEP
During the EARLY phase of sleep, release of ______________ hormone peaks.
During the MID phase of sleep, release of ______________ hormone peaks.
During the LATE phase of sleep, release of ______________ hormone peaks.
Growth hormone ;
Prolactin
ACTH
List all Hypothalamic releasing (& Inhibiting) hormones:
-Thyrotropin releasing hormone
-Gonadotropin releasing hormone
-Corticotropin releasing hormone
-GH releasing hormone
-GH inhibiting hormone
-Prolactin inhibiting hormone
ALL of the Hypothalamic releasing/ inhibiting hormones are ___________ type of molecule, EXCEPT ______________, which is a _____________ type of molecule.
Peptide ;
Prolactin inhibiting hormone (DOPAMINE)
=Catecholamine
_______________ is the MAIN regulator of Prolactin secretion.
Prolactin inhibiting hormone
Many hypothalamic & Pituitary peptide hormones are secreted in ____________ manner.
Pulsatile
(e.g. testosterone gets secreted every 60 or 90 minutes)
It is important to take at least 3 sample of blood drawn to get testosterone level:
Explain why:
Because the peptide hormones are secreted in pulsatile manner, is it more likely to get the basal levels of testosterone probabilistically → produce false negative reading. So you want to get 3 readings to hopefully catch the peak levels.
Key characteristics of Hypothalamic releasing hormones:
2 hormones produced by Posterior pituitary gland:
1. ADH (anti-diuretic; Vasopressin)
2. Oxytocin
ADH hormone targets ________________.
Oxytocin hormone targets ________________.
Kidney + blood vessels
Breast (+uterus)
(T/F) ALL endocrine systems in the body are essential for living & survival.
FALSE ;
There are hormones that can be turned off and you would still be able to live without difficulties.
Consequences of Adrenal pathophysiology:
-Abnormal sexual differentiation (females)
-Precocious puberty (males)
-Disturbed metabolic homeostasis
_______________ disease is when there's TOO MUCH adrenal function.
_______________ disease is when there's TOO LITTLE adrenal function.
Cushing disease
Addison disease
Upstream signals required for Adrenal cortex to secrete Adrenocortical steroids:
Hypothalamus secretes Corticotropin releasing hormone → Anterior pituitary secretes ACTH (Adrenocorticotropic hormone) → targets adrenal cortex
Upon stimulation by ACTH, Adrenal cortex secretes 3 hormones :
(order from greatest to least output)
#1. Cortisol
2. Adrenal androgens
3. Aldosterone
Explain the negative feedback mechanism in Hypothalamic-pituitary -adrenal axis :
When there's HIGH cortisol level, it will suppress anterior pituitary production of ACTH and Hypothalamic production of CRH to bring the system back to normal.
(once cortisol level is low, it will release this brake)
When there is a suppression of Cortisol by Metyrapone, ACTH level is going to (increase/ decrease).
Increase
(to compensate for reduction of cortisol)
The principle, DIRECT stimulator of ACTH?
Corticotropin-releasing hormone (CRH) from hypothalamus
What stimulates the release of CRH (Corticotropin-releasing hormone) from hypothalamus?
-Cortisol decrease (Adrenalectomy, metyrapone - negative feedback)
-sleep-wake transition
-STRESS
-Psychiatric disturbances (anxiety, depression)
List all Stimulators of ACTH from anterior pituitary :
(Refer to pic)
*STRESS is the main driver of system
*This system is an indicator of stress, depending on cortisol found in blood
_____________ hormones follow the SAME circadian pattern with that of ACTH profile.
Nocturnal secretion of these two hormones peak at _______________ (when)
Diurnal secretion of these two hormones peak at _______________ (when)
Cortisol
-Late phase of sleep ;
-Around sleep-wake transition period
Adrenal gland can be divided into two regions:
1. Cortex (80%)
2. Medulla (20%)
Name the major zones in Cortex and medulla of adrenal gland:
<Cortex>
-Glomerulosa
-Fasciculata
-Reticularis
<Medulla>
-Medulla
Cortisol (major glucocorticoid) is secreted from which region of adrenal gland?
Fasciculata zone of Adrenal CORTEX
(largest zone of adrenal gland making the hormone with largest output)
Aldosterone is synthesized in which region of adrenal gland?
Androgen is synthesized in which region of adrenal gland?
Glomerulosa of adrenal cortex
(most outer region of adrenal gland)
Reticularis zone of adrenal cortex
Epinephrine & Norepinephrine is synthesized in which region of adrenal gland?
Medulla
Which direction does the blood flow occur within the adrenal gland?
From Glomerulosa (cortex) to medulla
Basic structure of ALL steroidal hormones:
CHOLESTEROL
(21 carbons; 3x6-membered ring and 1 5-membered ring)
Which enzyme give substrate steroids for ALL steroid hormone synthesis?
P450 side chain cleavage (P450 scc)
a.k.a. ="Cholesterol desmolase"
What is the major role of Cholesterol desmolase enzyme?
Cleave off the STRETCH OF CARBONS of the cholesterol → to give rise to PRECURSOR molecule of ALL steroidal hormones called "Pregnenolone"
What is the COMMON Precursor of ALL steroidal hormones?
Pregnenolone
Which enzyme is responsible for converting Cholesterol to pregnenolone?
Cholesterol desmolase
(aka P450 scc)
The precursor cholesterol that give rise to all steroidal hormones initially start out with having ___________ (how many) carbons.
Androgens have ________ (how many) carbons
21
19
ALL 19-carbon steroids are _______________ hormones.
Androgens
______________ hormone is the most POTENT out of all glucocorticoids.
Cortisol
Which one is far more potent, Androgen or Testosterone?
Testosterone
50% of Adrenal androgen synthesis in FEMALES is __________________.
Androgens
Why are effects of Androgens NEGLIGIBLE in males?
B/c Testosterones are much more potent than Androgens that are "Weak androgens".
______________ are the "weak androgens".
Adrenal androgens
(Androgen hormones secreted from adrenal gland)
Adrenal androgens are prohormones for _________________ peripherally.
Testosterone
(Adrenal androgens can be converted to testosterone and raise its potency)
Adrenal androgens can be aromatized and converted into ______________.
Estrogens
Biosynthesis of secreted Adrenal glucocorticoids occur in ________________.
Fasciculata
What happens if there is a defect in 21β-hydroxylase or 11β-hydroxylase?
What if one of these defects are SEVERE?
Androgen OVERproduction
complete Cortisol & Aldosterone deficiency
Explain why defect in 21β-hydroxylase or 11β-hydroxylase cause ANDROGEN overproduction (even though these enzymes are not involved with androgen biosynthesis):
By blocking Cortisol and Aldosterone synthesis, it FEEDS BACK TO HYPOTHALAMUS and PITUITARY which sense the reduced level of cortisol & Aldosterone and starts pumping out CRH and ACTH for compensation. Since the two pathways are blocked, it has no option but to pick the route that synthesizes ANDROGENS.
90~95% of circulating CORTISOL is bound to :
-Transcortin (CBG)
or
-Albumin
(present for ALL sex steroidal hormones, not just cortisol)
2 major functions of Transcortin proteins:
1. Cortisol reservoir
2. Slows metabolism (increase half-life) of cortisol
Transcortins are synthesized in _______________ .
These proteins have high affinity for ______________.
Liver ;
Cortisol
(Free/ Bound) Cortisol is the biologically ACTIVE, bioavailable fraction.
FREE
Explain the importance of Cortisol binding to Transcortin proteins in circulation:
If all of the hormones in circulation were FREE and not bound to proteins, every time it passes through the capillary beds of LIVER, all those metabolites/ hormones would be DETOXIFIED, taken into blood, and excreted through kidney →→ Such high turnover rate makes adrenal gland over-work =huge demand on adrenal system.
2 Major characteristics of Cortisol:
-Catabolic
-Permissive (like catalyzing an action of other hormones)
List 3 classic clinical signs of Cushing's disease that exemplifies Cortisol's CATABOLIC actions:
-Muscle wasting
-Osteoporosis
-Diabetogenic
(Absence of insulin = catabolic; Insulin = anabolic)
Examples of the PERMISSIVE actions of Cortisol:
-Glycogenolysis by glucagon
-Gluconeogenesis by glucagon
-Tyrosine induction by tyrosine transminase
Cortisol acts on target tissues via ________________ mechanisms
Intracellular hormone RECEPTOR mechanism
MOA of Cortisol:
1) Cortisol binds to intracellular Glucocorticoid receptor on target tissue
2) Alters gene expression via glucocorticoid receptors (dimerization)
3) Facilitates mobilization of Fuels (primarily glucose under stressful conditions)
Explain how Cortisol MOBILIZES Fuel when the body is in fasting state:
-Cortisol gets secreted in high levels and binds to multiple glucocorticoid receptors throughout the body
-Brain →increase hunger & increase appetite
-Liver → promotes gluconeogenesis (conversion of amino acids to glucose) & glycogen breakdown
-Fat → LIPOLYSIS - promote breakdown of fat into free fatty acids for conversion into glucose
In absence of cortisol, death from ______________ occurs much sooner.
FASTING
Therapeutic effects of Cortisol:
-Anti-inflammatory
-Immunosuppressive
How does cortisol protect against stressors, such as trauma and infection, that require pro-inflammatory & pro-immunological defenses?
TIMING of response is regulated. Cortisol keeps inflammatory & Immune responses in check
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