Metabolism of steroid hormones

Question 1

What are steroids?

Answer 1

Lipophilic molecules that are derived from cholesterol

Question 2

What is the lipophilic property of steroids due to?

Answer 2

1. The non-polar fused ring structure
2. The hydrocarbon side chains
3. The minimal presence of polar functional groups

Question 3

How many major classes of steroid hormones are there?

Answer 3

5 major steorid classes

Question 4

What are the major classes of steroid hormones?

Answer 4

1. Progesterone
2. Testosterone
3. Estradiol
4. Aldosterone
5. Cortisol

Question 5

What is the function of progesterones?

Answer 5

Prepares the uterus for implantation and supports pregnancy

Question 7

What is an example of testosterone?

Answer 7

DHEA, a metabolite of testosterone, supports the embryonic development of the male phenotype

Question 8

What is the function of estradiol?

Answer 8

Promotes development of female sex characteristics

Question 9

What is the function of aldosterone?

Answer 9

Regulates salt balance and the volume and pressure of blood

Question 10

What is the function of cortisol?

Answer 10

Stimulates glucose and glycogen synthesis and inhibits the inflammatory response

Question 11

How do all steroid hormones operate?

Answer 11

Operate in a similar fashion: they bind to specific intracellular receptor proteins that subsequently regulate gene expression

Question 12

Where do all steroid hormones originate from?

Answer 12

Cholesterol, which is transported into the mitochondria for the first step of synthesis

Question 13

What is the steroidogenesis pathway like?

Answer 13

Cholesterol is converted into pregnenolone by CYP11A1, making it the rate-limiting step of steroidgenesis

Question 14

What is pregnenolone metabolised into?

Answer 14

Metabolized into three main pathways leading to the production of Glucocorticoids, mineralocorticoids, androgens and estrogens

Question 15

Which enzymes determine the direction of pregnenolone’s conversion into different steroid classes?

Answer 15

CYP17A1
CYP21A2

Question 16

What do enzyme mutations or deficiencies in CYP17A1 and CYP21A2 lead to?

Answer 16

Congenital adrenal hyperplasia

Question 17

What is the CYP17A1 inhibitor?

Answer 17

Abiraterone acetate

Question 18

What is abiraterone acetate?

Answer 18

CYP17A1 inhibitor and an inhibitor of androgen biosynthesis prolonged overall survival among patients with metastatic prostate cancer

Question 19

What are tissue-specific modifications?

Answer 19

Peripheral tissue can further metabolize these steroids, modifying their activity

Question 20

What does 5a-reductase do?

Answer 20

Converts testosterone to dihydrotestosterone, a more potent androgen

Question 21

What is the function of tissue-specific modifications?

Answer 21

This local metabolism modifies the activity, potency, or function of the hormones to meet the needs of the specific tissue

Question 22

What are the enzyme families that are involved in steroidogenesis?

Answer 22

CYP450 enzymes like CYP17A1, which catalyzes hydroxylation reactions

Hydroxysteroid dehydrogenases, or HSDs, which modify hydroxyketone groups

Question 23

What are the structural characteristics of steroid hormones?

Answer 23

They all share a structure, a series of four fused rings called cyclospentaperhydrophenantherene ring

The functional groups attached to this core determine what kind of adrenal cortex hormone it will be

Question 24

How can steroid hormones enter the cell?

Answer 24

Only the unbound, free fraction is active and can enter the cells

Question 25

What is the metabolism of steroid hormones like?

Answer 25

Biphasic

Question 26

What are the phases of the metabolism of the steroid hormones?

Answer 26

Phase 1: CYP3A4 in the liver adds hydroxyl groups, making the molecules slightly more water-soluble Phase 2: involves conjugation reaction like sulfation or glucuronidation

Question 27

What is the purpose of the functions that occur during the metabolism of steroid hormones?

Answer 27

They fully solubilize the steroids, preparing them for excretion

Question 28

What are the excretion pathways of the steroid hormones?

Answer 28

Conjugated steroid metabolites are excreted through urine or bile Measuring these metabolites in urine is a common diagnostic tool for endocrine disorders

Question 29

What is the transport and metabolism of steroid hormones like?

Answer 29

It is a tightly regulated process to ensure hormonal balance

Question 30

What is the general mechanism of steroid actions: genomic?

Answer 30

Unlike protein hormones, steroids diffuse across the cell membrane because they are lipophilic Inside the cell, they bind to specific receptors

Question 31

What are the different parts of the receptors that the steroid hormones bind to inside the cell?

Answer 31

1. Hormone binding site 2. DNA binding site 3. A site that activates transcription machinery to regulate gene expression

Question 32

What is the general mechanism of steroid actions (glucocorticoids)?

Answer 32

Cortisol increases anti-inflammatory proteins and decreases inflammatory gene expression. That is why it is used to treat conditions like asthma and arthritis

Question 33

What is the general mechanism of steroid actions (testosterone)?

Answer 33

An androgen that promotes muscle growth and male secondary sexual characteristics Estradiol: an estrogen, that regulates female reprodcution

Question 34

When are the genomic effects seen?

Answer 34

Within minutes, hours or days

Question 35

What is the general mechanism of steroid actions: nongenomic?

Answer 35

The nongenomic effects are believed to involve the direct binding of the extracellular GC-CBG complex to cell membrane receptors

Question 36

WHat is the effect of elevated levels of cortisol and the synthesis of GCs?

Answer 36

Known to exert rapid-onset, nongenomic effects that are seen within seconds or minutes and do not involve the GR or a change in the gene expression

Question 37

What are examples of nongenomic effects?

Answer 37

1. The rapid suppression of ACTH release 2. The inhibition of exocytosis in inflammatory cell types 3. The strong inhibition of growth hormone release

Question 38

What are disorders of steroidogenesis?

Answer 38

When steroid synthesis is disrupted, it leads to diseases like congenital adrenal hyperplasia, where enzyme defects cause hormone imbalances

Question 39

When does Addison's disease occur?

Answer 39

When cortisol levels are too low

Question 40

What type of synthetic glucocorticoids are widely used to treat inflammation?

Answer 40

Dexamethasone

Question 41

What does long term use of dexamethasone lead to?

Answer 41

Side effects like immune suppression