Steroid Biosynthesis Flashcards
What are all steroid hormones synthesized from?
Cholesterol
What enzyme controls the rate-limiting step of steroid hormone synthesis?
Desmolase
Desmolase activity is regulated by?
ACTH
What reaction is catalyzed by Desmolase?
Cholesterol –> Pregnenolone
Pregnenolone can then go on to create what other steroid hormones?
Aldosterone
Cortisol
Sex hormones - testosterone, estradiol, progesterone
Where does steroid hormone synthesis take place?
Adrenal cortex
Aldosterone can bind and activate what receptor?
Mineralcorticoid Receptor (MR)
Activation of the Mineralcorticoid Receptor results in what?
Increased Na+ retention = hypertension!
Primary Aldosteronism/Conn’s Syndrome
Adrenal glands produce too much Aldosterone!
Too much Aldosterone results in?
Retention of Na+
Loss of K+
Body holds on to too much water
Increased blood volume and blood pressure
Main result of Primary Aldosteronism/Conn’s Syndrome?
INCREASED BLOOD PRESSURE
Adrenal Hyperplasia
Deficiencies in adrenal enzymes that are used to make glucocorticoids
– This causes an increase in both cortisol PRECURSORS and androgens (sex hormones)
What are some signs of adrenal hyperplasia?
Life-threatening infections
Acne, short stature
Hirsutism
Oligomenorrhea and Infertility
Hirsutism
Male pattern body hair on women - seen with adrenal hyperplasia
Oligomenorrhea
Infrequent or light menstrual cycles - seen with adrenal hyperplasia
Cholesterol is converted to Pregnenolone
Pregnenolone is then converted to what 2 things?
Progesterone AND 17OH-progesterone
Progesterone is converted to what?
11-deoxycorticosterone
17OH-progesterone is converted to what?
11-deoxycortisol
What enzyme is responsible for creating 11-deoxycorticosterone and 11-deoxycortisol?
21-hydroxylase
11-deoxycorticosterone is converted to what?
Aldosterone
11-deoxycortisol is converted to what?
Cortisol
What enzyme is responsible for creating Aldosterone and Cortisol?
11beta - hydroxylase
Adrenal hyperplasia can be seen with the loss of what enzymes?
21 - hydroxylase
11beta - hydroxylase
11beta - hydroxylase deficiency
DECREASED aldosterone and cortisol
INCREASED 11-deoxycorticosterone and 11-deoxycortisol
11beta - hydroxylase deficiency results in what main symptom and why?
HIGH BLOOD PRESSURE because 11-deoxycorticosterone also has a high affinity to bind to the same receptor as aldosterone (MR)
– Thus you have high blood pressure even without the formation of aldosterone
What is the HPA for steroid hormones, specifically cortisol?
Hypothalamus - CRH
Anterior pituitary - ACTH
Adrenal glands - Cortisol
- Cortisol has (-) feedback on both CRH and ACTH
ACTH binds to what type of receptor in the Zona Fasciculata in the adrenal glands?
GPCR
What is the intracellular pathway events after ACTH binds to a GPCR in the adrenal gland?
Stimulates Adenylyl Cyclase
Increases cAMP
Activates protein kinase A
Creates cortisol
In a tumor cell, what is always active in the ACTH mediated intracellular signaling pathway?
protein kinase A
17,20 Lyase deficiency
Deficient production of androgens and 46XY development
Cholecalciferol (D3) can be formed in what 2 places in the body?
Skin and intestines
The skin creates D3 using?
7-dehydrocholesterol + UV light
The intestines creates D3 using?
D2 (Ergocalciferol)
Cholecalciferol (D3) is then transported from the skin and intestines to?
Liver
The liver takes cholecalciferol (D3) to?
25-hydroxycholecalciferol
The liver creates 25-Hydroxycholecalciferol using what enzyme?
25-hydroxylase
25-hydroxycholecalciferol is then sent to where?
Kidney
The kidney takes 25-hydroxycholecalciferol to what?
1,25 - dihydroxycholecalciferol = calcitriol
The kidney uses what enzyme to create calcitriol, the active form of Vitamin D?
1alpha-hydroxylase
What is the active form of Vitamin D?
1,25-dihydroxycholecalciferol (calcitriol)
Where is the active form of Vitamin D synthesized?
Kidney
