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Endocrinology and Reproduction > Adrenal Physiology I > Flashcards

Adrenal Physiology I Flashcards

1
Q

Unique in that they comprise two different endocrine tissues in one gland

A

Adrenals

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2
Q

The inner portion of the adrenal gland, which is composed of neurologic tissue

A

Adrenal Medulla

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3
Q

Functions in the synthesis and secretion of hormones derived from the amino acid tyrosine (termed catecholamines)

A

Adrenal Medulla

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4
Q

The outer portion of the adrenal gland, which is composed of glandular tissue

A

Arenal Cortex

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5
Q

The adrenal cortex functions in the synthesis and secretion of hormones derived from

A

Cholesterol (i.e. steroid hormones)

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6
Q

Elicits rapid stress responses

A

Catecholamine secretion

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7
Q

Typically elicits slower, more prolonged stress response

A

Steroid Hormone secretion

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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

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9
Q

Comprises almost 90% of the adult adrenal gland and can be subdivided into three layers or zones

A

Cortex

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10
Q

The outer most layer of the cortex is called the

A

Zona glomerulosa

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11
Q

The middle layer of the cortex is the

A

Zona fasciculata

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12
Q

The innermost region of the cortex is the

A

Zona reticularis

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13
Q

The zona glomerulosa exclusively synthesizes the steroid hormone

A

Aldosterone

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14
Q

The zona fasciculata and zona reticularis are primarily associated with the synthesis of

A

Cortisol and Androgen precursors

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15
Q

Derived from neuroectodermal cells and represents 10-20% of the adrenal gland by weight

A

Medulla

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16
Q

The catecholamine hormones epinephrine and norepinephrine are synthesized in the

A

Medulla

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17
Q

Epi and norepi are synthesized from tyrosine-derived precursors and are subsequently stored in the membrane bound

A

Chromaffin Granules

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18
Q

The enzymatic conversion of norepinephrin to epinephrine is positively regulated by the steroid hormone

A

Cortisol

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19
Q

The only direct communication between the cortex and Medulla

A

Cortisol

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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

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21
Q

As part of a ‘fight-or-flight’ response, SNS preganglionic stimulation of the adrenal medulla increases the rate of

A

Catecholamine synthesis

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22
Q

SNS stimulation also promotes the release of hormones from the

A

Chromaffin granules

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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

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24
Q

The metabolic actions of catecholamines are mediated via

A

a and B adrenergic receptors

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25
Q

Increase glucose production by stimulating gluconeogenesis and glycogenolysis in the liver

A

Both types of catecholamines

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26
Q

Can selectively induce splanchnic, renal, cutaneous and genital arteriolar vasoconstriction via a-receptors

A

Norepinephrine

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27
Q

All steroid hormones originate from

A

Cholesterol

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28
Q

Cholesterol used for steroid hormone synthesis is predominantly derived from circulating cholesterol in the plasma bound to

A

Low-density lipoproteins (LDLs)

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29
Q

Accordingly, adrenocortical cells have particularly high levels of cell surface LDL-receptors that transfer cholesterol into the cell by

A

Endocytosis

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30
Q

In addition, cholesterol can also be biochemically synthesized within adrenal cells via an

A

Acetyl-CoA precursor

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31
Q

Once inside the adrenal cell, cholesterol is esterified and stored in cytoplasmic

A

Lipid vacuoles

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32
Q

Steroid hormone biosynthesis occurs through several steps. First, esterified cholesterol is hydrolyzed into free cholesterol and actively transported to the outer membrane of nearby

A

Mitochondria

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33
Q

Second, cholesterol is transferred to the inner mitochondrial membrane where it becomes a substrate for a

A

Cytochrome P-450 enzyme

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34
Q

This cytochrome P-450 enzyme converts cholesterol into

A

Pregnenolone

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35
Q

Pregnenolone is then transferred out of the mitochondria and into the

A

Endoplasmic Reticulum (ER)

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36
Q

In the ER, pregnenolone is the

A

Hydroxylated

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37
Q

Subsequently, the steroids are transferred back into the mitochondria where they undergo final

A

Hydroxylation events

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38
Q

The end products rapidly diffuse out of the cell and into the blood stream. What are the three end products?

A
  1. ) Glucocorticoids
  2. ) Mineralocorticoids
  3. ) Androgenic precursors
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39
Q

The rate limiting step in steroid hormone biosynthesis is the conversion of cholesterol into

A

Pregnenolone

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40
Q

What is the rate limiting substrate in the conversion of cholesterol into pregnenolone?

A

Cholesterol

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41
Q

This rate limiting step is catalyzed by the mitochondrial cholesterol side chain cleavage enzyme known as

A

CYP11A

42
Q

Removes the side chains of cholesterol and replaces it with an acetyl group

A

CYP11A

43
Q

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?

A

Mineralocorticoids, glucocorticoids, and androgenic precursors

44
Q

The zona glomerulosa lacks the enzyme complex CYP 17 (17α-hydroxylase/17, 20-lyase) yet exclusively expresses the enzyme

A

Aldosterone synthase

45
Q

Thus, the principle mineralocorticoid produced in the zona glomerulosa is

A

Aldosterone

46
Q

Aldosterone’s formation starts with progesterone and proceeds through a series of hydroxylations in the ER followed by a hydroxylation event in the

A

Mitochondria

47
Q

Note that 11-deoxycorticosterone and corticosterone also contain modest

A

Mineralocorticoid activity

48
Q

The predominant, and most physiologically potent glucocorticoid produced in the adrenal cortes is

A

Cortisol

49
Q

The major negative feedback regulator of the adrenocortical steroidogenesis

A

Cortisol

50
Q

Cortisol’s production affects the synthesis of all other adrenal steroids except

A

Aldosterone

51
Q

The principal androgenic precursors produced

by the adrenal cortex are

A

Dehydroepiandrosterone (DHEA) and Androstenedione

52
Q

The result of 17- hydroxylation of either pregnenolone or progesterone followed by 17,20-desmolase activity

A

DHEA and Androstenedione

53
Q

Neither DHEA nor androstenedione have significant intrinsic biological activity and are primarily active only after conversion to

A

Testosterone and Estrogen

54
Q

Binds to receptors in the zona fasiculata and zona reticularis and activates the biosynthesis of cortisol and androgen precursors

-pituitary hormone

A

Adrenocorticotropic hormone (ACTH)

55
Q

Requires An-II binding to receptors in the zona glomerulosa

A

Aldosterone synthesis

56
Q

ACTH production in the pituitary is controlled by a 41

amino acid neuropeptide synthesized and secreted by the hypothalamus termed

A

Corticotropin-releasing Hormone (CRH)

57
Q

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

A

Corticotrophic cells (ATCH producing cells)

58
Q

In response to CRH, the corticotrophic cells of the pituitary produce and release

A

ACTH

59
Q

ACTH interaction with specific membrane receptors

triggers cAMP production that acts to stimulate

A

Steroidogenesis

60
Q

Acute stimulation by ACTH enhances steroidogenesis by facilitating the rate-limiting conversion of cholesterol to

A

Pregnelenone

61
Q

This occurs by ACTH upregulation of

A

CYP11A

62
Q

Also, to facilitate this rate limiting step, ACTH activates the three phosphoproteins known as

A
  1. ) Steroidogenesis activator protein
  2. ) Sterol transfer protein
  3. ) Steroidogenic acute regulatory protein (StAR)
63
Q

Promote the hydrolysis of stored cholesterol esters and their subsequent active transport to and into the mitochondria

A

The three phosphoproteins

64
Q

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

A

Chronic ACTH stimulation

65
Q

Long term ACTH stimulation also exerts a tonic effect on the adrenal cortex increasing both the size and number of adrenocortical cells and their

A

Mitochondria

66
Q

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

A

Cortisol (but not other steroid hormones)

67
Q

Plasma cortisol concentrations and levels of other adrenal steroids are increased by

A

Environmental stress

68
Q

These increases are predominantly due to adrenal responsiveness to

A

CRH-ATCH endocrine signaling

69
Q

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

A

Morning when you wake and during periods prior to routine eating

70
Q

The lowest rates of ACTH and cortisol secretion occur right after you

A

Fall asleep

71
Q

Once secreted into the blood stream, more than 90% of cortisol is bound to

A

Corticosteroid-Binding Globulin (CBG) (aka transcortin)

72
Q

A liver derived carrier protein which serves to protect cortisol from metabolism in the liver and subsequent renal clearance

A

CBG (transcortin)

73
Q

Also acts as a mobile reservoir of cortisol, providing it to peripheral tissues

A

CBG (transcortin)

74
Q

By contrast, binds only weakly to serum carrier proteins and is rapidly metabolized in the liver

A

Aldosterone

75
Q

What is the estimated 1/2 life of

  1. ) CBG
  2. ) Aldosterone
A
  1. ) 80-100 min

2. ) 15 min

76
Q

Cortisol is in equilibrium with its biologically inactive 11-keto-analog

A

Cortisone

77
Q

Cortisol is in equilibrium with cortisone, its biologically inactive 11-keto-analog, via the enzyme

A

11β-hydroxysteroid dehydrogenase (11-HSD)

78
Q

There are two different sub-types of 11-HSD. Which type is found in the liver, pituitary, muscle, gonads, and adipose?

A

Type 1 11-HSD

79
Q

Uses NDPH to reduce cortisone into cortisol

A

Type 1 11-HSD

80
Q

Type 2 11-HSD is found in the

A

Kidney and other aldosterone target tissues

81
Q

Oxidizes cortisol into cortisone using ND

A

Type 2 11-HSD

82
Q

Effectively inhibits cortisol from acting as a mineralocorticoid receptor agonist

A

Type 2 11-HSD

83
Q

Thought to primarily play a protective role inhibiting promiscuous activation of the mineralocorticoid receptor

A

Type 2 11-HSD

84
Q

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

A

1:1

85
Q

Cortisol is metabolized in the liver into tetrahydrocortisol and then cortol, while cortisone
is metabolized into tetrahydrocortisone and then

A

Cortolone

86
Q

Thee corticosteroid metabolites are then conjugated with glucuronic acid and excrete into the urine as

A

Glucurondes

87
Q

In individuals with normal kidney and hepatic functions, the measurement of excreted “17-hydroxycorticoids” is a reliable clinical index of

A

The bodies cortisol production

88
Q

Normal urine excretion rates of 17-hydroxycorticoids range from

A

2-12 mg/day (slightly higher in men)

89
Q

The juxtaglomerular cells of the kidney respond to decreased blood volume by synthesizing and secreting the proteolytic enzyme

A

Renin

90
Q

ACE is especially prominent in the vascualr epithelium of the

A

Lungs

91
Q

Affects the zona glomerulosa by enhancing the production of pregnenolone from cholesterol as well as stimulating the later steps of the aldosterone biosynthesis pathway

A

An-II

92
Q

Thought to be involved in the production of aldosterone

A

Calcium and diacylglycerol secondary messenger systems

93
Q

The rate determining step in An-II production is the conversion of

A

Angiotensinogen into An-I

94
Q

Thus, aldosterone production is regulated by the secretion of

A

Renin

95
Q

In addition to An-II, aldosterone secretion can be activated by elevated

A

Serum K+ (and to a lesser degree ACTH)

96
Q

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

A

ACTH

97
Q

Ligand-induced transcription factors

A

Steroid hormone receptors (nuclear hormone receptors)

98
Q

Activated steroid hormone receptors interact with specific DNA sequences termed

A

Hormone response elements (HREs)

99
Q

Usually found upstream from the regulatory regions (enhancers) of specific genes

A

HREs

100
Q

Thus, the major effect of steroid hormones is to increase the synthesis of specific

A

Proteins

Endocrinology and Reproduction (15 decks)

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