Steroid Hormones and Vit D

Question 1

Do steroid hormones enter the cell or do they bind receptors on the membrane? How do steroid hormones travel through the blood?

Answer 1

enter the cell

albumin/coticosteroid-binding globulin/aka transcortin/carrier proteins

Question 2

What is the rate limiting step of steroid hormone synthesis? and what catalyzes this reaction?

Answer 2

conversion of cholesterol to the 21 carbon pregnenolone

catalyzed by cholesterol side chain cleavage enzyme- Aka desmolase, CYP11A and P450scc

Question 3

What mediates cholesterol movement from the outer mito membrane to the inner membrane where the CYP11A exists?

Answer 3

Steroidogenic acute regulatory protein (StAR)

Question 4

Conversion of Pregnenolone–> progesterone involves what enzyme and a deficiency in this enzyme causes what?

Answer 4

3-B-hydroxysteroid dehydrogenase

Deficiency–no glucocorticoids/mineralocorticoids/active adrogens/estrogens

• salt excretion in urine
• female like genitalia

Question 5

Conversion of Progesterone–> 17-a-hydrocyprogesterone involves what enzyme and a deficiency in this enzyme causes what?

Answer 5

17-a-hydroxylase (CYP17)

Deficiency- No sex hormones or cortisol

• increased production of mineralocorticoids–fluid and na retention–HTN
• Female-like genitalia

Question 6

Conversion of progesterone –> 11-deoxycorticosterone and 17-a-hydroxyprogesterone–> 11-deoxycortisol involve the same enzyme, what is it and a deficiency in it causes what?

Answer 6

21-a-hydroxylase

Deficiency- mineralocorticoids and glucocorticoids absent
-overproduction of androgens leading to masculinization of external genitalia in females and early visualization in males

Question 7

Conversion of 11-deoxycorticosterone–> corticosterone and 11-deoxycortisol–> cortisol involve the same enzyme, what is it and a deficiency in it causes what?

Answer 7

11-B-hydroxylase (CYP11B1)

Deficiency- decrease in serum cortisol/aldosterone/corticosterone

• increased production of deoxycorticosterone–fluid retention—-low renin HTN
• overproduction of androgens fuses masculinization and visualization as with 21-a-hydroxylase deficiency

Question 8

What is the mechanism for Cortisol release?

Answer 8

Stress–> hypothalamus–> CRH–> anterior pituitary–> ACTH–> adrenal medulla (zona fasciculata)–> cortisol

Increase cortisol causes negative feedback on CRH and ACTH release

Question 9

Does ACTH work through a 2nd messenger system? if so what is activated?

Answer 9

Yes– leads to increased cAMP which activates PKA–> cholesterol ester conversion to cholesterol and StAR activation allowing cholesterol to move to inner mito membrane where its converted to pregnenolone…

Question 10

What hormone is released from the zone glomerulosa, what triggers its release and what is its effect?

Answer 10

Aldosterone–> stimulated by decrease in plasma Na/K ratio and angiotensin II

primary effect is upon kidney tubules where it enhances Na and water uptake and K efflux

Increases blood pressure and ACE inhibitors are used to treat renin dependent HTN

Question 11

What is the role of LH and FSH and where are they released from?

Answer 11

LH–testes=testosterone/ovaries=estrogen,progesterone
FSH- ovarian follicle growth and spermatogenesis

Released from zona reticularis of the adrenal cortex

Question 12

How is testosterone synthesized from estrogen?

Answer 12

Aromatase enzyme

Question 13

What does the steroid hormone bind to in the cell and what effect does this have?

Answer 13

hormone response element (HRE)
-found in the promoter or an enhancer element for genes that are responsive to a specific steroid hormone

• Coactivators- increase mRNA transcription
• corepressors- decrease transcription

Question 14

What is the active form of Vit D and what is its most important function?

Answer 14

1,25-diOH-D3/calcitriol

-regulate plasma levels of Ca and Phosphorous

Question 15

What are the exogenous and endogenous sources of Vit D?

Answer 15

Exogenous- Ergocalciferol D2 from plants and Cholecalciferol D3 from animals

Endogenous- 7-dehydrocholesterol
–converted to cholecalciferol in the dermis/epidermis when exposed to sunlight

Question 16

What are D2 and D3 covered to in the liver?

Answer 16

25-OH-D3/calcidiol–major form of Vit D in the plasma and major storage form

Question 17

What occurs in the kidney to Vit D?

Answer 17

25-OH-D3 is convered to 1,25-diOH-D3/calcitriol–active form of Vit D

Question 18

What regulates 25-hydroxycholecalciferol 1- hydroxylase? Enzyme used for conversion of 25-OH-D3–> 1,25-diOH-D3

Answer 18

Activity is increased with decreased plasma phosphate levels (directly) and by low plasma Ca (indirectly–through PTH secretion from the parathyroid)

Negative feedback loop exist for both

Question 19

When there is low plasma Ca what occurs?

Answer 19

Increased 1,25-diOH-D3 and PTH–both act to increase Ca absorption and bone resorption and inhibit Ca excretion

Question 20

When there is high plasma Ca what occurs?

Answer 20

block production of PTH–results in conversion of 25-OH-D3 to 24,25-diOH-D3 instead of 1.25diOH-D3

decreased PTH and 1,25-diOH-D3 causes elevated expression of calcitonin resulting in inhibition of bone resorption and enhanced Ca secretion

Question 21

What does Vit D deficiency cause in children and adults? what does this cause?

Answer 21

children- Nutritional rickets–demineralization of bone–formation of collagen matrix with insufficient mineralization –> soft and pliable bones

Adults- osteomalacia–demineralization of existing bones makes them more susceptible to fracture.