Biochemistry-Steroid Synthesis Flashcards
5 classes of steroid hormones
1) Progesterons (21C) 2) Glucocorticoids (21C) 3) Mineralocorticoids (21C) 4) Androgens (19C) 5) Estrogens (18C)
Where are most steroid receptors located?
Since steroids are lipophilic, receptors are found intracellularly in the cytosol or in the nucleus
How does cortisol turn genes on?
It binds the glucocorticoid receptor and allows the receptor to dimerize with another receptor. It can then interact with DNA sequences to turn genes on that raise blood glucose levels

What stimuli do the brain and kidney send to the adrenal gland (glucocorticoids, mineralocorticoids, and androgens) or gonads (androgens, estrogens or progestagens) to produce steroids?
ACTH (ant. pit), FSH (ant. pit), LH (ant. pit), Angiotensin (kidney) and oxytocin (hypothalamus)
What is the target tissue of the hormone listed below?

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How does angiotensin II stimulate cellular signaling to increase aldosterone production?
ATII -> Gq -> PLC -> PIP2 -> IP3 (opens Ca channels) and DAG (activates PKC which stimulates aldosterone production)

How do ACTH/FSH/LH stimulate cellular signaling to increase steroid synthesis?
Hormone -> G-protein -> Adenylyl cyclase -> cAMP -> PKA -> Steroid synthesis

What types of steroid hormones are secreted by the adrenal cortex?
Aldosterone (zona glomerulosa, “salt steroid”), Cortisol (zona fasciculata, “sugar steroid”) and Androgens (zona reticularis, “sex steroid” in males)

HPA axis
Hypothalamus secretes CRH -> Pituitary releases ACTH -> Adrenal releases cortisol. This all happens in response to hypothalamic stimulation by sleep, cold, pain, emotions, hemorrhage, exercise, hypoglycemia, infections, trauma, toxins etc.

What effect does cortisol have on muscle glucose uptake, glucose use, protein synthesis, glucose output, ketogenesis and glycogenolysis?
Increased glucose output, ketogenesis and glycogenolysis. Decreased muscle glucose uptake, glucose use and protein synthesis.
3 symptoms of glucocorticoid deficit
Hypoglycemia (insulin uninhibited and glucagon unstimulated), fatigue (low glucose/gluconeogenesis) and infection (loss of inflammation & infection control)
Distal tubule reaction to aldosterone
Increased water and Na uptake and K excretion
Kidney response to decreased BP
Juxtaglomerular cells secrete the enzyme renin -> AT -> ATI -> ATII by ACE -> ATII causes aldosterone release from adrenal cortex -> salt and water retention -> increased BP

3 symptoms of mineralocorticoid deficit
Electrolyte imbalance (hyponatremia, hyperkalemia), Dehydration & diarrhea (Na excretion) and low BP (RAAS ineffective)
3 effects of testosterone
Anabolic (muscle/bone growth), androgenic (secondary sex characteristics in males) and promotes differentiation of spermatogonia
2 types of testosterone
Testosterone and DHT (more potent)
What causes progesterone synthesis and what are its effects?
FSH stimulates corpus luteum and placenta to make progestagens. Progesterone prepares uteral lining during ovulation and maintains pregnancy
3 types of estrogens
Estradiol (E2 is most predominant, most potent), estriol (E3, made in placenta), estrone (E1, major source in post-menopausal women)
Where does steroid synthesis take place after PKA is activated?
Smooth ER and mitochondria

Sources of cholesterol for steroid synthesis
1) LDL (80%), also from scratch and cholesterol ester droplets
What stimulates LDL receptors to bring in more cholesterol for steroid synthesis?
Binding of hormone to receptor. Note that binding of the receptor also stimulates upregulation of CYP450 side chain cleaving enzyme for steroid synthesis
Rate limiting and committed step for steroid synthesis?
Cholesterol (C27) -> Pregnenolone (C21) by CYP450 side chain cleaving enzyme

As an overview how does steroid synthesis progress?
More oxidation as the pathway goes on and loss of carbons to form androgens and estrogens.

Precursor for mineralocorticoid and glucocorticoid synthesis
Progesterone. Remember that aldosterone has an aldehyde at C18 and that cortisol has an alcohol at C17.





