MECH 430 Lecture Notes - Lecture 12: Zona Fasciculata, Zona Glomerulosa, Zona Reticularis

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Lecture 12
The Adrenal Gland
o Chronic stressors result in adrenal gland to be
hyperactive
o Paired glands with total weight of 8-10 g
situated above or medial to the upper poles
of the kidneys
o Large blood supplies to these blood vessels
that are drained into the arterial system
o Surrounded by fibrous capsule and adrenal
divided into functional layers
o Cortex is about 90% of adrenal mass, inner
medulla is about 10%
o Cortex has 3 zones: zona f. is the thickest about
75% of the cortex
o The synthesis of cortisol is from the zona
fasciculata
Figure 21. Schematic showing the cellular zonation of
the adrenal cortex and blood flow through the cortex to
the collection veins in the medulla
o This anatomical arrangement is important for
cortisol being carried into the medulla for the
reaction to synthesis epi and no-epi
o Release of cortisol directly into the body is not as
effective and takes longer, thus this arrangement
allows us to synthesis high levels of cortisol
without dilution in the blood
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The hormones of the adrenal glands
o Zona gloerulosa aldosterone
o Zona fasciculate cortisol
o Zona reticularis sex steroids
o Medulla catecholamines (epinephrine and norepinephrine)
Steroid Biosynthesis
o Tissue specificity of the reactions in steroid biosynthesis
o Zona glomerulosa lacks 17-hydroxylase, therefore cannot
synthesize either cortisol or androgens
o There are different enzymes in different pathways to allow
for the derivation of different compounds
o It is matter of locating an enzyme in a particular tissue that
forces the biosynthesis and the type of steroid that will be
produced
o Do not need to memorize all these different pathways, but
understand that the presence or absence of 17a-hydrozylase’s
effect
o The key is the first step of converting cholesterol to
pregnenolone all our our steroids are derived from the
cholesterol ring structure that is ubiquitous across our body
We have dietary sources or our body can also
biosynthesis it
Synthesis of steroid hormones
o Derived from cholesterol
o Main source is the diet, but can also be synthesized from acetyl-CoA
o Tissue specific expression of enzymes determines what steroid is produced in a cell or tissue
o Some enzymes are located in the mitochondria others in the endoplasmic reticulum
Steroid intermediates have to shuttle back and forth
When we are synthesizing these compounds, we are shuttling them out into the
cytoplasm, back into the mitochondria and back in to synthesis the different types of
steroids
o Most steroids differ by minor modifications of side groups, often hydroxyl groups
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Example: Synthesis of aldosterone
o StAR transports cholesterol (rate limiting step) across the mitochondrial membrane to P450scc
(side chain cleavase)
o This rate limiting protein is the rate limiting protein that helps bring the molecule into the inner
surface of the mitochondria to remove the cholesterol chain at the end of the molecule to form
the pregnenolone
Progesterone is produced outside the mitochondria, etc follow the pathway in the
image above
The end product of aldosterone is formed inside the mitochondria and then shuttled out
into the cytosol
The Initiation of Steroidogenesis
o The first step common to all steroids is the formation of pregnenolone from cholesterol
o Takes place in the mitochondria
o Uptake of cholesterol is the rate limiting step and regulated by StAR protein
StAR = Steroid Acute Regulatory Protein
StAR is a cAMP-inducible and increases in response to trophic hormones
I.e. ACTH in the adrenal gland and gonadotrophins in the gonads, respectively
o On inner mitochondrial membrane side chain of cholesterol is cleaved by P450scc (side chain
cleavase) to produce pregnenolone
o Activation with ACTH results in the biosynthesis of various proteins, such as stAR that allows us
to take cholesterol across the cell membrane into the inner cell membrane to form prenenolone to
synthesis the particular steroid we want
The first step is to stimulate the production of a required enzyme in that given pathway
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Document Summary

75% of the cortex: the synthesis of cortisol is from the zona fasciculata. The hormones of the adrenal glands: zona gloerulosa aldosterone, zona fasciculate cortisol, zona reticularis sex steroids, medulla catecholamines (epinephrine and norepinephrine) Function of the zona fasciculata (cortisol: main steroid produced is cortisol, no cellular storage of cortisol, converted to inactive cortisone and other metabolites by the liver (for excretion in urine) and by other target cells. In some cells, cortisone can be reconverted to cortisol: main effects, carbohydrate and protein metabolism, anti-inflammatory effects acts on the immune system. Effect of cortisol on intermediary metabolism: overall: anabolic effect in the liver. Increases of blood glucose despite the increase in glycogen storage. Treatment for cushing"s syndrome: treatment is aimed at removing the cause of hypersecretion, without permanently damaging the adrenal or pituitary, would require lifelong replacement therapy, microsurgery remove tissue that is oversecreting to restore back to equilibrium. Acth secretion: we treat it based on what the cause is.

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