Adrenal Gland Phys Flashcards
Adrenal Gland composed of what two areas?
Cortex and Medulla
Adrenal cortex is located where in relation to the medulla
Periphery
What types of hormones does the adrenal cortex make?
Steroids
Three regions of the adrenal cortex
zona glomerulosa (15%) zone fasiculata (75%) zona reticularis (10%)
What does the zona glomerulosa make?
Aldosterone
What do the zona fasiculates and zona reticularis make?
Glucocorticoids (cortisol), SAndrogens and Estrogens
Adrenal Medulla makes?
Catecholamines (Epinephrine and Norepinephrine)
See slides and hormone table bs for function of the hormones
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Transport of adrenocortical hormones in blood is facilitated by what?
steroid hormone-binding serum proteins called GLOBULINS
-partially by albumin which has low affinity
90% of Cortisol exists in what form
BOUND, moslty to transcortin and partially to albumin
10% of cortisol in plasma is :
FREE
60% of aldosterone is bound to?
Transcortin
Purposes of hormone binding protein:
- suppress the biological activity of steroid hormones
- protect the hormone from structural alteration
- Extend the half-life of hormones
- Provide an active hormone to the target tissue when needed
What is teh source of all steroid hormones
cholesterol duh.
What provides the cholesterol
LDL (80% cholesterol for steroid synthesis)
How cholesterol get into adrenal cells for steroid synthesis
LDL binds to LDL receptors (clathrin coated pits) on the plasma membranes of adrenal cortical cells
LDL is transported into the cells by what process
endocytosis (endosomal membrane trafficking)
In lysosomes cholesterol is released from the receptors
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Cholesterol is then esterified and stored in cytoplasmic vesicles until it is needed for steroid synthesis
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Key enzyme in steroid synthesis
KNOW
cholesterol desmolase (cyp11A1) part of the P450 superfamily - facilitates the conversion of cholesterol to pregnenolone
What controls steroidogenesis
ACTH stimulates CYP11A1
- also stimulates cholesterol uptake by upregulating LDL receptors
Besides Desmolase, what is the other key enzyme in mineralocorticoid biosynthesis
Aldosterone Synthase
What upregulates desmolase activity?
ACTH…you know this
What upregulates aldosterone synthase
Ang II
What is the final step of mineralocorticoid biosynthesis?
corticosterone to aldosterone
Target organs for aldosterone
kidneys, brain, lungs, heart, vascular
What is the mechanism of mineralocorticoid effect?
Upregulates gene expression:
1) binds to MR’s in the cytoplasm
2) The hormone receptor complex translocates to the nucleus
3) Binding to the promoter area of specific genes
4) Upregulation of gene expression (Na/K ATPase, Na, K transporters
Genes that are upregulated by the mineralocorticoids?
- Na/K ATPase…ATP dependent transport of Na and K
- Epithelial sodium channel (ENaC
- Serum and Glucocortocoid regulated kinase 1 (SGK1)
- Renal outer medullary K channel
—Important to note that SGK1 activates Na/K ATPase, ENac, and ROMK)
GLucocorticoids are produced where?
Zona Reticularis and Zona Fasiculata (main site of synthesis)
most potent glucocorticoid
Cortisol (hydrocortisone)…95% os glucoccorticoid activity
Corticosterone
modest potency
What are the key enzymes in cortisol biosynthesis that we should know
- cholesterol desmolase
- 11beta hydroxylase
What drug inhibits desmolase action?
ketaconazole
What drug inhibits 11beta hydroxylase action
Metapyrone and Etomidate
Glucoccorticoids (cortisol) affect on the liver
promotes gluconeogenesis from amino acids, mobilization of amino acids from muscle into blood
Cortisol on pancreas?
upreg insulin production
cortisol’s affect on various organs?
Upregulate insulin resistance
KNOW that glucocorticoids stimulate protein catabolism in all organs except the liver
ok. This means that proteins are broken down to amino acids, you have more amino acids in the blood, decreased protein synthesis mean sloss of body wt. and immune function suppresed
Gluccocorticoids and fat metabolism
Promotes lipolysis, enhance mobilization and oxidation of fatty acids as an alternative enrgy source.
-Redistribution of body fat (paradoxical fat deposits in the body)
High doses of oral cortisol can lead to what?
Cushing’s syndrome
What does Cortisol do to immune function
Suppresses it
EFFEcts of Cortisol on other tissues
notes
Describe transactivation and transpression as they apply to glucocorticoid effect on gene expression
transactivation- stimulation or repression of gene expression
transpression- suppression of genes via transcriptional factors
Adrenal sex hormones and males
weak effects
Adrenal sex hormones in women
The major Androgens (excess leads to suppression of gonadal function and masculinization) This is called adrenogenital syndrome
The hormones of the adrenal medulla are?
Epinephrine, Norepinephrine
What is the structure of epinephrine and norepinephrine?
amino acid derivatives (tyrosine)
Remember that the cells of the medulla are neuroectodermal in origin and therefore are modified neurons
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Targets of catecholamines?
heart, lungs, muscles, vessels
Hypothalamic pituitary adrenal axis does what?
manages tress response, energy usage, immune response, digestion
Corticotrophin releasing hormone stimulates the pituitary to secrete ACTH
ACTH stimulates the adrenal cortex to produce its hormones….KNOW
Cortisol initiates a negative feedback regulation by inhibiting the hippocampus, hypothalamus,and pituitary gland
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