Adrenal Physiology I Flashcards
(100 cards)
1
Q
Unique in that they comprise two different endocrine tissues in one gland
A
Adrenals
2
Q
The inner portion of the adrenal gland, which is composed of neurologic tissue
A
Adrenal Medulla
3
Q
Functions in the synthesis and secretion of hormones derived from the amino acid tyrosine (termed catecholamines)
A
Adrenal Medulla
4
Q
The outer portion of the adrenal gland, which is composed of glandular tissue
A
Arenal Cortex
5
Q
The adrenal cortex functions in the synthesis and secretion of hormones derived from
A
Cholesterol (i.e. steroid hormones)
6
Q
Elicits rapid stress responses
A
Catecholamine secretion
7
Q
Typically elicits slower, more prolonged stress response
A
Steroid Hormone secretion
8
Q
The adrenal cortex arises from mesodermal tissue and produces a distinct class of lipid-soluble hormones derived from cholesterol called
A
Steroid hormones
9
Q
Comprises almost 90% of the adult adrenal gland and can be subdivided into three layers or zones
A
Cortex
10
Q
The outer most layer of the cortex is called the
A
Zona glomerulosa
11
Q
The middle layer of the cortex is the
A
Zona fasciculata
12
Q
The innermost region of the cortex is the
A
Zona reticularis
13
Q
The zona glomerulosa exclusively synthesizes the steroid hormone
A
Aldosterone
14
Q
The zona fasciculata and zona reticularis are primarily associated with the synthesis of
A
Cortisol and Androgen precursors
15
Q
Derived from neuroectodermal cells and represents 10-20% of the adrenal gland by weight
A
Medulla
16
Q
The catecholamine hormones epinephrine and norepinephrine are synthesized in the
A
Medulla
17
Q
Epi and norepi are synthesized from tyrosine-derived precursors and are subsequently stored in the membrane bound
A
Chromaffin Granules
18
Q
The enzymatic conversion of norepinephrin to epinephrine is positively regulated by the steroid hormone
A
Cortisol
19
Q
The only direct communication between the cortex and Medulla
A
Cortisol
20
Q
A component of the sympathetic nervous system (SNS) and in essence, can be thought of as a large sympathetic ganglion without postganglionic processes
A
Adrenal Medulla
21
Q
As part of a ‘fight-or-flight’ response, SNS preganglionic stimulation of the adrenal medulla increases the rate of
A
Catecholamine synthesis
22
Q
SNS stimulation also promotes the release of hormones from the
A
Chromaffin granules
23
Q
Rather than being secreted into a neuronal synapse, epi and norepi are secreted directly into the blood stream and thus are not classified as neurotransmitters, but rather as
A
Hormones
24
Q
The metabolic actions of catecholamines are mediated via
A
a and B adrenergic receptors
25
Increase glucose production by stimulating gluconeogenesis and glycogenolysis in the liver
Both types of catecholamines
26
Can selectively induce splanchnic, renal, cutaneous and genital arteriolar vasoconstriction via a-receptors
Norepinephrine
27
All steroid hormones originate from
Cholesterol
28
Cholesterol used for steroid hormone synthesis is predominantly derived from circulating cholesterol in the plasma bound to
Low-density lipoproteins (LDLs)
29
Accordingly, adrenocortical cells have particularly high levels of cell surface LDL-receptors that transfer cholesterol into the cell by
Endocytosis
30
In addition, cholesterol can also be biochemically synthesized within adrenal cells via an
Acetyl-CoA precursor
31
Once inside the adrenal cell, cholesterol is esterified and stored in cytoplasmic
Lipid vacuoles
32
Steroid hormone biosynthesis occurs through several steps. First, esterified cholesterol is hydrolyzed into free cholesterol and actively transported to the outer membrane of nearby
Mitochondria
33
Second, cholesterol is transferred to the inner mitochondrial membrane where it becomes a substrate for a
Cytochrome P-450 enzyme
34
This cytochrome P-450 enzyme converts cholesterol into
Pregnenolone
35
Pregnenolone is then transferred out of the mitochondria and into the
Endoplasmic Reticulum (ER)
36
In the ER, pregnenolone is the
Hydroxylated
37
Subsequently, the steroids are transferred back into the mitochondria where they undergo final
Hydroxylation events
38
The end products rapidly diffuse out of the cell and into the blood stream. What are the three end products?
1. ) Glucocorticoids
2. ) Mineralocorticoids
3. ) Androgenic precursors
39
The rate limiting step in steroid hormone biosynthesis is the conversion of cholesterol into
Pregnenolone
40
What is the rate limiting substrate in the conversion of cholesterol into pregnenolone?
Cholesterol
41
This rate limiting step is catalyzed by the mitochondrial cholesterol side chain cleavage enzyme known as
CYP11A
42
Removes the side chains of cholesterol and replaces it with an acetyl group
CYP11A
43
Pregnenelone is transported out of the mitochondria and into the ER where it now becomes a substrate for alternative biosynthetic pathways which yeild which three major classes of adrenocortical steroids?
Mineralocorticoids, glucocorticoids, and androgenic precursors
44
The zona glomerulosa lacks the enzyme complex CYP 17 (17α-hydroxylase/17, 20-lyase) yet exclusively expresses the enzyme
Aldosterone synthase
45
Thus, the principle mineralocorticoid produced in the zona glomerulosa is
Aldosterone
46
Aldosterone's formation starts with progesterone and proceeds through a series of hydroxylations in the ER followed by a hydroxylation event in the
Mitochondria
47
Note that 11-deoxycorticosterone and corticosterone also contain modest
Mineralocorticoid activity
48
The predominant, and most physiologically potent glucocorticoid produced in the adrenal cortes is
Cortisol
49
The major negative feedback regulator of the adrenocortical steroidogenesis
Cortisol
50
Cortisol's production affects the synthesis of all other adrenal steroids except
Aldosterone
51
The principal androgenic precursors produced
| by the adrenal cortex are
Dehydroepiandrosterone (DHEA) and Androstenedione
52
The result of 17- hydroxylation of either pregnenolone or progesterone followed by 17,20-desmolase activity
DHEA and Androstenedione
53
Neither DHEA nor androstenedione have significant intrinsic biological activity and are primarily active only after conversion to
Testosterone and Estrogen
54
Binds to receptors in the zona fasiculata and zona reticularis and activates the biosynthesis of cortisol and androgen precursors
-pituitary hormone
Adrenocorticotropic hormone (ACTH)
55
Requires An-II binding to receptors in the zona glomerulosa
Aldosterone synthesis
56
ACTH production in the pituitary is controlled by a 41
| amino acid neuropeptide synthesized and secreted by the hypothalamus termed
Corticotropin-releasing Hormone (CRH)
57
In response to environmental stimulus via the CNS, CRH is released from the hypothalamus into the hypophyseal portal system and directed towards
-In the anterior pituitary
Corticotrophic cells (ATCH producing cells)
58
In response to CRH, the corticotrophic cells of the pituitary produce and release
ACTH
59
ACTH interaction with specific membrane receptors
| triggers cAMP production that acts to stimulate
Steroidogenesis
60
Acute stimulation by ACTH enhances steroidogenesis by facilitating the rate-limiting conversion of cholesterol to
Pregnelenone
61
This occurs by ACTH upregulation of
CYP11A
62
Also, to facilitate this rate limiting step, ACTH activates the three phosphoproteins known as
1. ) Steroidogenesis activator protein
2. ) Sterol transfer protein
3. ) Steroidogenic acute regulatory protein (StAR)
63
Promote the hydrolysis of stored cholesterol esters and their subsequent active transport to and into the mitochondria
The three phosphoproteins
64
Further induces the expression of cell-surface LDL receptors and the production of specific steroid biosynthetic enzymes (i.e., 17-hydroxylase) such that cortisol is the principal product of the biosynthetic pathway
Chronic ACTH stimulation
65
Long term ACTH stimulation also exerts a tonic effect on the adrenal cortex increasing both the size and number of adrenocortical cells and their
Mitochondria
66
Exerts a negative feedback on ACTH production by direct inhibition of ACTH gene expression in the pituitary and also inhibition of CHR release from the hypothalamus
Cortisol (but not other steroid hormones)
67
Plasma cortisol concentrations and levels of other adrenal steroids are increased by
Environmental stress
68
These increases are predominantly due to adrenal responsiveness to
CRH-ATCH endocrine signaling
69
There is also a circadian rhythm of ACTH (and thus cortisol) secretion based primarily on sleep/wake, light/dark, and feeding cycles, with the highest rates of secretion occurring both in the
Morning when you wake and during periods prior to routine eating
70
The lowest rates of ACTH and cortisol secretion occur right after you
Fall asleep
71
Once secreted into the blood stream, more than 90% of cortisol is bound to
Corticosteroid-Binding Globulin (CBG) (aka transcortin)
72
A liver derived carrier protein which serves to protect cortisol from metabolism in the liver and subsequent renal clearance
CBG (transcortin)
73
Also acts as a mobile reservoir of cortisol, providing it to peripheral tissues
CBG (transcortin)
74
By contrast, binds only weakly to serum carrier proteins and is rapidly metabolized in the liver
Aldosterone
75
What is the estimated 1/2 life of
1. ) CBG
2. ) Aldosterone
1. ) 80-100 min
| 2. ) 15 min
76
Cortisol is in equilibrium with its biologically inactive 11-keto-analog
Cortisone
77
Cortisol is in equilibrium with cortisone, its biologically inactive 11-keto-analog, via the enzyme
11β-hydroxysteroid dehydrogenase (11-HSD)
78
There are two different sub-types of 11-HSD. Which type is found in the liver, pituitary, muscle, gonads, and adipose?
Type 1 11-HSD
79
Uses NDPH to reduce cortisone into cortisol
Type 1 11-HSD
80
Type 2 11-HSD is found in the
Kidney and other aldosterone target tissues
81
Oxidizes cortisol into cortisone using ND
Type 2 11-HSD
82
Effectively inhibits cortisol from acting as a mineralocorticoid receptor agonist
Type 2 11-HSD
83
Thought to primarily play a protective role inhibiting promiscuous activation of the mineralocorticoid receptor
Type 2 11-HSD
84
The plasma concentration of cortisone is
roughly 1/5 that of cortisol, yet because cortisone binds only weakly to CBG, the plasma ratio of free cortisol to free cortisone is close to
1:1
85
Cortisol is metabolized in the liver into tetrahydrocortisol and then cortol, while cortisone
is metabolized into tetrahydrocortisone and then
Cortolone
86
Thee corticosteroid metabolites are then conjugated with glucuronic acid and excrete into the urine as
Glucurondes
87
In individuals with normal kidney and hepatic functions, the measurement of excreted “17-hydroxycorticoids” is a reliable clinical index of
The bodies cortisol production
88
Normal urine excretion rates of 17-hydroxycorticoids range from
2-12 mg/day (slightly higher in men)
89
The juxtaglomerular cells of the kidney respond to decreased blood volume by synthesizing and secreting the proteolytic enzyme
Renin
90
ACE is especially prominent in the vascualr epithelium of the
Lungs
91
Affects the zona glomerulosa by enhancing the production of pregnenolone from cholesterol as well as stimulating the later steps of the aldosterone biosynthesis pathway
An-II
92
Thought to be involved in the production of aldosterone
Calcium and diacylglycerol secondary messenger systems
93
The rate determining step in An-II production is the conversion of
Angiotensinogen into An-I
94
Thus, aldosterone production is regulated by the secretion of
Renin
95
In addition to An-II, aldosterone secretion can be activated by elevated
Serum K+ (and to a lesser degree ACTH)
96
Is capable of acute stimulation of aldosterone synthesis, but over time acts more to stimulate cortisol and androgen precursor production by facilitating the conversion of glomerulosa to fasciculata cells
ACTH
97
Ligand-induced transcription factors
Steroid hormone receptors (nuclear hormone receptors)
98
Activated steroid hormone receptors interact with specific DNA sequences termed
Hormone response elements (HREs)
99
Usually found upstream from the regulatory regions (enhancers) of specific genes
HREs
100
Thus, the major effect of steroid hormones is to increase the synthesis of specific
Proteins
