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Endocrine
4. Adrenal: Biochemistry And Physiology
71
Medical
Graduate
01/22/2008

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Cards

Term
The adrenal consists of two distinct secretory glands within a single capsule. How much percent of the  total gland does each constitute, what embryological origin does it come from, and what does it secrete?
Definition
  • Cortex is yellow due to high fat content, constitues 80% of total gland, is derived from mesoderm, and manufactures steroid hormones.
  •  
  • The medulla is red due to rich blood supply, constitues 20% of total gland,is derived from neuroectoderm, and synthesizes catecholamines
Term
What are the 3 different secretory cells of the adrenal?
Definition
  1. zona glomerulosa
  2. zona fasciculata
  3. zona reticularis 
Term
The zona glomerulosa cells constitute 5% of the adrenal and they exclusively synthesize..
Definition
Aldosterone
Term
The zona fasciculata cells constitute 80% of the adrenal and they exclusively synthesize..
Definition
Cortisol, the most potent glucocorticoid.
Term
What 2 hormones does the zona reticularis synthesize?
Definition
Androstenedione and dehydroepiandrosterone (DHEA). there extra-adrenal conversion of those two to testosterone and estrogen and thus considered sex hormone precursors.
Term
what supplies the adrenal with fresh blood and what drains it?
Definition
Each adrenal is supplied by aorta, renal artery, and inferior phrenic; but each is drained by just a single central vein.
Term

True or False

 

In the adrenal, blood flow directionally is from outer cortex to the medulla; basal flow is high and can increase substantially  during stress, a response mediated by pituitary secretion of adrenocorticotrophic hormone (ACTH) 

Definition
True
Term

The increase in intravascular pressure within the adrenal during stress predisposes the it to spontaneous massive bilateral hemorrhage, especially in patients with hemorrhagic diatheses such as those on anticoagulants or anti-platelet agents. What are 2 physiologic reasons that effect this predisposition?
 

Definition
  1. The fact that the central vein draining each side is under constant concentrated catecholamine exposure causes it to constrict.
  2. Exposure of the adrenals to high basal arterial pressure.
Term

True or False

 

Spontaneous bilateral adrenal hemorrhage is an important and sometimes unrecognized cause of acute adrenal insufficiency, a life-threatening condition in which profound hypotension is usually the cardinal and sometimes the only clinical finding. 

Definition
True
Term
In the fetus when is the adrenals histologically recognizable?
Definition
2 months gestation
Term
During fetal life what are the names of the layers constituting the adrenals?
Definition

10% "definitive" cortex

90% "fetal" zone 

Term
after birth this layer of the adrenal regresses. what is it? and when does it regress?
Definition
fetal zone; by 1 year
Term
  1. zona glomerulosa and fasciculata become  fully developed when?
  2.  zona fasciculata is formed when and fully developed when?
Definition
  1. between 1-3 years.
  2. formed by 1year & fully developed by puberty 
Term
what does the fetal 'definitive' zone produce, and how does that change with the growing fetus?
Definition
25% of fetal plasma cortisol, the rest is derived from the mother via transplacental transport. However, by term, about 75% of fetal plasma cortisol is derived from the developing outer zone of adrenal and only 25% from the mother.
Term
what is the predominant hormone of the fetal zone of the developing adrenal gland, and what is its role?
Definition
DHEA. it serves as a precursor for synthesis of  placental & circulating estrogen.
Term

True or False

 

Fetal adrenal androgen production is a determinate of the sexual phenotype of the newborn, that is of differentiation of the external genitalia. 

Definition
True
Term

 When do DHEA and androstenedione levels from a developing zona reticularis begin to increase?

Definition
Between ages 7-9 years.
Term
What is “Adrenarche”?
Definition
The increase in adrenal androgen production which mediates physiologic changes consisting of a brief pre-pubertal growth spurt and the appearance of pubic and axillary hair.. occurs around 7-9 years of age.
Term
Adrenal DHEA production and plasma levels of DHEA continue to change as a function of age, reaching a peak at what age?
Definition
3rd decade, and declines thereafter.
Term
pituitary ACTH, adrenal cortisol or aldosterone secretion reach adult levels at a certain age and remain constant throughout life in healthy adults. what is that age bracket?
Definition
by 1 to 3 yrs of age.
Term
All human steroid hormones are derived from what?
Definition
cholesterol.
Term
The initial and rate limiting biosynthetic step in the conversion of cholesterol to steroids is what?
Definition
cleavage of the cholesterol side chain to generate a C21 four ringed structure (pregnenolone).
Term
The adrenal cortex synthesizes all classes of steroids in variable amounts including small quantities of estrogen and testosterone. Indeed, most of the steroid biosynthesis pathway is shared by the gonads and adrenal cortex.  However, only the adrenal synthesizes cortisol and aldosterone, why?
Definition
this require expression of 11Beta hydroxylase activity and aldosterone synthase activity, respectively.  The latter two enzymes are not expressed in gonadal cells.
Term

True or False 

 

the enzyme which catalyzes cholesterol side chain cleavage and the gene which encodes it are both identified as CYP11A1.   Some genes encode more than one enzymatic activity,  for CYP11B2 (aldosterone synthase).

Definition
True
Term

True or False 

 

Steroid hormones are synthesized as needed in response to physiologic regulators and are not stored within the adrenal.

Definition
True
Term
The concentration of this hormone in the plasma is highly dependent upon salt intake and hemodynamics.
Definition
Aldosterone
Term

True or False

 

Of the major adrenal steroids, only cortisol circulates predominately bound to a high affinity transport protein.  Approximately  90% of circulating  cortisol  is bound to cortisol binding globulin (CBG or transcortin), an alpha-globulin synthesized in liver.   

Definition
True.
Term

True or False

 

Cortisol bound to cortisol binding globulin (CBG or transcortin) is biologically INACTIVE cortisol. 

Definition
True.
Term
Estrogen increases CBG and total cortisol levels.  Nephrotic syndrome lowers total plasma cortisol due to loss of large quantities of CBG through urine.  In both conditions, why do patients not have manifestations of cortisol deficiency?
Definition
In both conditions, what changes really is CBG, while unbound cortisol remains unchanged.  Unbound, free, cortisol is the biologically active form and is thus unaffected.
Term
How are steroid hormones inactivated? How are they excreted?
Definition
hepatically inactivated & excreted in the urine.
Term
At its highest concentration in the plasma, this hormone's concentration in the plasma at any one moment remains the lowest amongst the other adrenal hormones.  It also has the lowest production rate (mg/day) as compared to the rest of the hormones.
Definition
Aldosterone with 0.01 - 0.02 ug/dl.
Term
What enzyme catalyzes the extra-adrenal conversion of adrenal androgens to estrogen? Where is it located.
Definition
Enzyme P450 aromatase; it is located in fat cells.
Term
Why do circulating estrogen levels generally increase as a function of body fat content?
Definition
Fat cells express the P450 aromatase enzyme which converts adrenal androgens to estrogen.  As fat cells increase, so does expression of the enzyme.
Term
What is the primarly responsible for the regulation of the synthesis and secretion of aldosterone by glomerulosa cells?
Definition
renin-angiotensin system
Term

True or False

 

Normal basal secretion of ACTH and cortisol occurs in a pulsatile pattern and demonstrates a circadian rhythm which follows the sleep-wake cycle. 

Definition
True
Term

True or False 

 

First, “normal” values for plasma cortisol are dependent on the time of day.  Thus, typical 8:00AM plasma cortisol values are in the 15-20 ug/dl range, whereas early evening values are typically less than 10 ug/dl.  Second, about 65% of total daily adrenal secretion of cortisol (~15 mg/day) occurs between 6:00AM and 2:00PM.

Definition
True
Term
when prescribing basal cortisol replacement therapy for patients with adrenal insufficiency, how is the dose adjusted?
Definition
Adjusted to reflect that in normal subjects the majority of cortisol release occurs in the morning with levels decreasing through the afternoon and evening.  So, two-thirds of the total daily dose is given in the morning and one-third in the evening.
Term

True or False

 

A variety of acute and chronic stressful stimuli, including vigorous exercise, cold exposure, fever, hypotension, trauma and hypoglycemia, acting through incompletely defined central nervous system pathways stimulate hypothalamic secretion of CRH, and consequently secretion of ACTH and cortisol. 

Definition
True.
Term
What are 3 acute effects of ACTH on the adrenal gland?
Definition

Increases:

  1.  Blood flow
  2. Cholesterol -> pregnenlone
  3. Cortisol (2-5min)
Term
What are 3 chronic (via cAMP response elements (CRE)) effects of ACTH on the adrenal gland?
Definition
Increases:
  1. adrenal mass
  2. synthesis of steroidogenic enzymes
  3. LDL receptors 
Term
Low plasma cortisol and high plasma ACTH signals what kind of condition?
Definition
Primary adrenal failure
Term
How can you discern a secondary adrenal failure by just looking at the levels of cortisol and ACTH?
Definition
both levels of ACTH and cortisol should be low.
Term
The genomic mechanisms for expression of the actions of all steroid hormones on cells are similar. What kinds of plasma membrane receptors do cells have to effect such signals?
Definition

  Cells possess no such membrane receptors for the genomic effects of steroid hormones; in fact those pathways rely on receptors internal to the cells.

 

As with other steroids,a steroid hormone (G) is thought to enter cells by passive diffusion across the plasma membrane and then bind to a specific cytoplasmic receptor protein (R).  The GR complex then mediates the cellular actions via the genomic pathways.

Term
Explain the 2 genomic pathways by which glucocorticoids mediate their action on cells.
Definition
They bind w/cytoplasmic receptor and enter the nucleus  to  bind to regulatory squences forming a glucocorticoid response element (GRE) and function as transcription factors.

The glucocorticoid steroid/receptor complex binds to cytoplasmic protein, thereby inhibiting their action - one such example is NF-kappaB.
Term

True or False

 

The actions of glucocorticoids mediated by their genomic effects take hours to days.

Definition
True.
Term

True or False

 

The non-genomic actions of glucocorticoids takes minutes rather hours to days. 

Definition
True
Term

True or False

 

The potency of steroid hormones as glucocorticoids correlates with their affinity for the Type 2, glucocorticoid, receptor. 

Definition
True
Term

True or False

 

The potency of steroid hormones as mineralocorticoids DOESN't correlate with their affinity for the Type 1, mineralocorticoid receptor.

Definition
True.
Term

True or False 

  

 In contrast with Type 1 mineralocorticoid receptors whose distribution of cellular expression is more limited, glucocorticoid receptors are ubiquitous in their cellular distribution.  The biologic actions of glucocorticoids are correspondingly very diverse.

Definition
True
Term
What are the 3 effects of glucocorticoids on carbohydrate metabolism?
Definition
  1. Maintain hepatic glycogen stores.
  2. Maintain hepatic gluconeogenesis;and the actions of epinephrine and glucagon on this process.   
  3. Reduce peripheral glucose utilization (muscle, fat).
Term
What is the mechanism by which glucocorticoids mediate maintaining of hepatic glycogen stores?
Definition
Activate glycogen synthase; inactivate phosphorylase.
Term
What is the mechanism by which glucocorticoids mediate maintaining hepatic gluconeogenesis?
Definition
Mobilize gluconeogenic precursors (amino acids, glycerol). Activate gluconeogenic enzymes (glucose-6-phosphatase, PEPCK)
Term
What is the mechanism by which glucocorticoids mediate reducing peripheral glucose utilization (muscle, fat)?
Definition
Reduced insulin action in part via decreasing GLUT 4 mediated glucose transport.
Term
What are the 2 effects of glucocorticoids on lipid metabolism?
Definition
  1. Acute – activation of lipolysis at some sites with release of fatty acids, glycerol.
  2. Chronic – Central fat accumulation with chronic excess of cortisol.
Term
What is the mechanism by which glucocorticoids induce lipid metabolism acute effect (activation of lipolysis at some sites with release offatty acids, glycerol)?
Definition
Increased sensitivity to lipolytic actions of catecholamines and hGH;reduced fat cell glucose uptake.
Term
What is the mechanism by which glucocorticoids mediate lipid metabolism chronic effect (Central fataccumulation with chronic excess of cortisol)?
Definition
Uncertain, associated with increased insulin levels which may interactwith cortisol to increase lipogenesis at central sites.
Term
What is the effect of glucocorticoids on protein metabolism?
Definition
Protein loss from muscle, connective tissue in skin, bone, other sites with release of amino acids.
Term
What is the mechanism by which glucocorticoids mediate protein metabolism effects?
Definition
Increase proteolysis; suppress synthesis; some extracellular matrix proteins;fibroblast growth
Term
What is the effect of glucocorticoids on bone?
Definition
Osteopenia
Term
What is the mechanism by which glucocorticoids mediate their effect on bone (osteopenia)?
Definition
Inhibit osteoblast activity and thus suppress bone formation; suppress release of cytokines involved in osteoblast regulation.
Term
What is the effect of glucocorticoids on the GI system?
Definition
Suppress GI absorption of calcuim.
Term
What is the mechanism by which glucocorticoids mediate their effects on the GI (decrease Ca++ absorption)?
Definition
Reduced GI sensitivity to 1,25(OH)2D.
Term
What are the effects of glucocorticoids on the cardiovascular system?
Definition
Maintain normal cardiac output and vasomotor tone.
Term
What is the mechanism by which glucocorticoids mediate their effects on the cardiovascular system?
Definition
Not fully understood; increases sensitivity of the vessels to catecholamines and other pressors; increases receptor numbers for vasopressors; increases smooth muscle cell Ca2+ uptake; suppress vasodilator (PGs and NO) synthesis
Term
What are the 2 renal effects of glucocorticoids?
Definition
  1. Maintain of normal free  water clearance.
  2. Sodium retention, potassium wasting and hypertension. 
Term
What is the mechanism by which glucocorticoids mediate maintenance of normal free water clearance?
Definition
Tonic suppression of ADH release and maintenance of normal cardiac output.
Term
What is the mechanism by which glucocorticoids mediate sodium retention, potassium wasting and hypertension?
Definition
Mineralocorticoid action of very high levels of cortisol in kidney via the Type 1 receptor.
Term
What effects CNS do glucocorticoids have?
Definition
Modulate mood, sleep-patterns, cognition, behavior. Their mechanism of actinon is uncertain.
Term
What hematological effects do glucocorticoids have?
Definition
Maintain normal erythropoiesis(anemia with cortisol deficiency and polycythemia with excess). Their mechanism of action their is uncertain.
Term
What anti-inflammatory effects do glucocorticoids have?
Definition
Suppress multiple mediators of inflammation; suppress T-lymphocyte function; suppress B-lymphocyte eosinophil and macrophage
function and numbers.
Term
What is the mechanism by which glucocorticoids mediate their anti-inflammatory effects?
Definition
Inhibit NF-kappaB mediated gene transcription. Reduce production of inflammatory cytokines, (ILs, TNF, PGs, leukotrienes).
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