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35 Cards in this Set

  • Front
  • Back
Give a few examples of water insoluble lipophilic hormones.
Steroids, amines (thyroxin, triiodothyronine), FA derivatives (eicosanoids), Vitamin D
Where are lipophilic hormones stores within a cell?
They are not stored; they are constitutively synthesized and released.
What do lipophilic hormones bind to in plasma and what affect does this binding have?
Specific plasma carrier proteins.
Binding increases their solubility, life span, and stabilizes concentration of free hormone.
Where to lipophilic hormones bind on their target cells?
To intracellular receptors.
Give a few examples of hydrophilic hormones.
Amines (dopamine, epi, NE), peptides (oxytocin, ADH), proteins (GH, insulin), glycoproteins (FSH, TSH).
Where are hydrophilic hormones stored inside the cell?
In secretory granules usually.
Where do hydrophilic hormones bind on their target cell?
Membrane receptors.
Where are steroid hormones synthesized?
In the adrenal gland, testes, ovaries, placenta, and adipose tissue.
Where and from what are steroid hormones synthesized?
In the intermembrane space of the mitochondria from cholesterol.
How is cholesterol made?
From acetate, cholesterol ester stores in intracellular lipid droplets, or from uptake of cholesterol-containing low density lipoproteins (LDLs).
Breakdown steroid biosynthesis.
Cholesterol is converted to pregnenolone via CYP11A1. Through multiple oxidative enzymatic tranformations, pregnenolone can be converted into:
Glucocorticoids (cortisol)
Mineralocorticoids (aldosterones)
Androgens
Estrogens
Progestins
(Thus inactive--> active)
Where is pregnenolone in a cell?
Pregnenolone moves between the mit and the ER.
Is cholesterol hydrophilic or hydrophobic?
Both; cholesterol is amphipathic and thus can easily cross the cell membrane.
Is Vitamin D2 hyprophilic or lipophilic? Vitamin D3?
They are both lipophilic.
How are Vit D2 and D3 activated?
Both must undergo dihydroxylation (one hydroxylation in the liver, the second in the kidney)
How are Vit D2 and VitD3 obtained?
Vit D2: dietary uptake.
Vit D3: synthesized in skin from cholesterol precursor under UV light
What are the thyroid hormones produced from the AA tyrosine and are they lipophilic or hydrophilic?
T4 (thyroxine) and T3 (triiodothyronine). Lipophilic
What is the fate of hydrophobic hormones?
Diffuse out of endocrine cell into blood--> immed bind to transport proteins in blood--> diffuse out of blood and into target cell--> bind to nuclear receptors--> induce transcription
What are eicosanoids?
FA derivatives from an arachidonic acid precursor. (lipophilic hormones)
They usually act locally on a very short half-life (sec-min)
What are the two enzymes that convert arachidonic acid to eicosanoids (and what molecules do they make?)?
Cyclooxygenase-->prostaglandins
Lipoxygenase-->Leukotrienes
What are prostaglandins' main functions?
Affecting platelet aggregation, promoting SM contraction (raising BP, increasing uterine contractions).
What are leukotrienes' main functions?
Mediate inflammation, bronchioconstriction.
What do NSAIDs like ibuprofen, naproxen, and aspirin usually target?
Cyclooxygenase (COX), the enzyme that converts arachidonic acid to prostaglandins (eicosanoids).
When are lipophilic hormones released into blood?
Immediately after synthesis.
When are lipophilic hormones released from carrier proteins in the blood?
When the unbound (or free) concentration of hormone drops, as an equilibrium between bound and unbound hormones is maintained.
Hence measuring free hormone in blood does not accurately reflect available hormone.
Breakdown the biosynthesis of peptides and proteins.
Translation of ER-bound ribosomes--> polypeptide chains inserted into lumen of ER--> proteins folded in ER--> correctly folded proteins transported to cis-Golgi--> cistrenal progression from cis to trans-Golgi--> mature proteins packaged in secretory vesicles
How and where is proinsulin activated?
Proinsulin is post-translationally proteolytically cleaved into an active hormone by beta cell peptidases in secretory vesicles in the beta cells of the pancreas
How is POMC (proopiomelanocortin) activated?
It is post-translationally proteolytically cleaved to form multiple active hormones, with the only human physiological hormone being ACTH.
What are the catecholamine hormones derived from the AA tyrosine and are they lipophilic or hydrophilic?
Epi and NE. Hydrophilic.
How are hydrophilic hormones stored?
How are they secreted?
In secretory vesicles (because they cannot cross the lipid bi-layer).
Ex: in adrenal chromaffin cells, and pituitary lactrotroph
They are secreted from the endocrine cell into ECspace through exocytosis.
How is exocytosis a therapeutic agent?
BoTox (cleaves SNARES, thus preventing synaptic transmission).
Sulfonylureas: antihyperglycemic by inducing ATP-indep't K+ channel closure in the beta cell, thus potentiating insulin secretion
What is the fate of hydrophilic hormones in the blood?
Endocrine cell secretes active hormones (bc prohormones were cleaved and activated in endocrine cell) which diffuse to the blood--> hormones circulate unbound--> diffuse out of blood and activate surface rec on target cell--> act via second messengers
How are hydrophilic hormones broken down?
Some are broken down in their end organ, but most circulating hormones are broken down to inactive metabolites in the liver
What are a couple common causes of hypofunction in endocrine pathology?
Autoimmune destruction, genetic defects in hormone synth pathways/ hormone rec/ intracellular signaling pathways.
What is the usual cause of endocrine hyperfunction?
Tumors. Ectopic hormone production by tumors is quite common (eg adrenal carcinomas secreting a lot of androgens--> hirsutism in female pts)