Biochem: Steroids and Prostaglandins Flashcards
Name the 3 groups of corticosteroids.
Where are they synthesised?
Mineralocorticoids (Aldosterone)
Glucocorticoid (Cortisol)
Androgen (DHEA)
Made in the adrenal glands
Name the 3 groups of gonadal steroids.
Where are they synthesised?
Progesterone
Androgen (Testosterone)
Oestrogens (Estradiol)
What molecule are all steroid hormones made from?
Cholesterol
What are the 4 major sources of cholesterol?
De novo (from acetate)
plasma membrane
Intracellular lipid droplets
Plasma lipoproteins (low density lipoprotein cholesterol)
What is the rate limiting step of steroid synthesis?
Where does it occur?
Removal of 6 carbons from cholesterol (C27) to progesterone (pregnenolone) (C21)
Cataylsed by p450 (CYP11A1) in the inner mitochondrial membrane facing the matrix.
Which protein is deficient in embryos affected by congenital adrenal hyperplasia?
StAR steroidogenic acute regulator protein - prevents transport of cholesterol into mitochondria in adrenal glands. No corticosteroids produced.
What is the importance of CYP (p450) enzymes in steroid biosynthesis?
Catalyse hydroxylation reactions to increase solubility of the steroid hormones in aqueous medium.
Transport of electron from NADPH, ferredoxin reductases, ferredoxin and cytcrome p450
What is the importance of hydroxysteroid dehydrogenase (HSD) enzymes?
Catalyse the oxidation of secondary alcohol groups +/- reduction of ketone groups at specific carbon positions.
Steroid biosynthesis depends on the CYP and HSD expression in a particular tissue.
What is synthesised in the following cells:
1) Testies Leydig cells
2) Ovarian follies theca cells
3) Follicular granulosa cells
4) Luteal cells with Corpus Luteum
1) Testosterone
2) Androstenedione
3) Convert androstenedione to estrone to estradiol
4) Progesterone and estradiol
Why is the placenta unable to produce androgens?
What organs does it reply on for estogen synthesis?
It is an incomplete endocrine gland and does not express CYP17A which is required to convert progesterones into androgens. It relies on fetal adrenal glands and the mothers liver.
What steroid is unique to the placenta and can be used as a marker of fetal adrenal gland functional marker?
Estriol
Enzyme secreted from fetal adrenal gland, which in the placenta is aromatised to estriol.
How are steroid hormones excreted from the body?
Rendered more hydrophilic so they can pass out in urine or faeces. 2 step catalysis mainly in the liver.
Name the 5 steroid hormone receptors and there corresponding ligand.
Progesterone receptor - progesterone
Mineralcorticoid receptor - Aloosterone (and deoxycorticosterone)
Glucocorticoid receptor - cortisol
Androgen receptor - 5 a-DHT (and testosterone)
Estrogen receptor - estradiol (and esterone)
Where are steroid hormone receptors located
Intracellular - hydrophobic steroid hormones can cross the plasma membrane
Generally what affect of steroid hormones on DNA?
When steroid hormone receptors are actived - they bind to DNA to specific nucleotides sequences often in promotor regions which modulate transcription of target genes. They can either repress or activate gene transcription.
Typically how long does it take for steroid to change cellar function by changing gene expression?
6 hours to several days
What is the name of the membrane phospholipid that all prostaglandins are synthesised from?
Arachidonic acid
Which enemze liberates arachidonic acid from the plasma membrane acting as the rate limiting step?
Phospholipase A2
Which enzyme acts on arachidonic acid to synthesis prostaglandin H2?
Cyclooxygenase (COX)
Described the 2 forms of COX enzyme
What are they inhibited by?
COX 1 - active isoenzyme
COX 2 hormone responsive/inducible
Indometacin and other NSAIDS
What are the 4 forms of prostglandsin converted from PGH2
PG: D2, E2 F2a I2
How is inactivation of prostaglandins achieved
Oxidation of alcohol group at carbon position 15, relies on 15-hydroxyprotoglandin
How do prostaglandins change cell function
G couple receptors on cell surface and increasing or decreasing amount of second messengers.
How quickly do prostaglandins change cell function
seconds to minutes
Which hormones increase frquency/force myometrium contractions.
oxytocin and prostaglandins (PGf2a)
What do oxytocin and prostaglandins (PGf2a) both activate? What does this cause?
Phospholipase C leading to increase in intracellular Ca2+
Where does contracting oxytocin originate
Uterus
Which steroids increase the expression of oxytocin and prostgland F2a
Estradiol and cortisol
Also positive feedback on each other
Which hormones acts as anticontractant
NO
Relaxin
Progesterone
What happens at term to the level of progesterone. What impact dos this have?
Switch from predominantly relaxant progesterone to more estradiol required for onset of labour
