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Endocrine System > Metabolism of steroid hormones > Flashcards

Metabolism of steroid hormones Flashcards

1
Q

What are steroids?

A

Lipophilic molecules that are derived from cholesterol

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2
Q

What is the lipophilic property of steroids due to?

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

How many major classes of steroid hormones are there?

A

5 major steorid classes

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4
Q

What are the major classes of steroid hormones?

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

What is the function of progesterones?

A

Prepares the uterus for implantation and supports pregnancy

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6
Q
A
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7
Q

What is an example of testosterone?

A

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

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8
Q

What is the function of estradiol?

A

Promotes development of female sex characteristics

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9
Q

What is the function of aldosterone?

A

Regulates salt balance and the volume and pressure of blood

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10
Q

What is the function of cortisol?

A

Stimulates glucose and glycogen synthesis and inhibits the inflammatory response

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11
Q

How do all steroid hormones operate?

A

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

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12
Q

Where do all steroid hormones originate from?

A

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

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13
Q

What is the steroidogenesis pathway like?

A

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

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14
Q

What is pregnenolone metabolised into?

A

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

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15
Q

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

A

CYP17A1
CYP21A2

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16
Q

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

A

Congenital adrenal hyperplasia

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17
Q

What is the CYP17A1 inhibitor?

A

Abiraterone acetate

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18
Q

What is abiraterone acetate?

A

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

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19
Q

What are tissue-specific modifications?

A

Peripheral tissue can further metabolize these steroids, modifying their activity

20
Q

What does 5a-reductase do?

A

Converts testosterone to dihydrotestosterone, a more potent androgen

21
Q

What is the function of tissue-specific modifications?

A

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

22
Q

What are the enzyme families that are involved in steroidogenesis?

A

CYP450 enzymes like CYP17A1, which catalyzes hydroxylation reactions

Hydroxysteroid dehydrogenases, or HSDs, which modify hydroxyketone groups

23
Q

What are the structural characteristics of steroid hormones?

A

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

24
Q

How can steroid hormones enter the cell?

A

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

25
Q

What is the metabolism of steroid hormones like?

A

Biphasic

26
Q

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

A

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

27
Q

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

A

They fully solubilize the steroids, preparing them for excretion

28
Q

What are the excretion pathways of the steroid hormones?

A

Conjugated steroid metabolites are excreted through urine or bile

Measuring these metabolites in urine is a common diagnostic tool for endocrine disorders

29
Q

What is the transport and metabolism of steroid hormones like?

A

It is a tightly regulated process to ensure hormonal balance

30
Q

What is the general mechanism of steroid actions: genomic?

A

Unlike protein hormones, steroids diffuse across the cell membrane because they are lipophilic

Inside the cell, they bind to specific receptors

31
Q

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

A
  1. Hormone binding site
  2. DNA binding site
  3. A site that activates transcription machinery to regulate gene expression
32
Q

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

A

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

33
Q

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

A

An androgen that promotes muscle growth and male secondary sexual characteristics

Estradiol: an estrogen, that regulates female reprodcution

34
Q

When are the genomic effects seen?

A

Within minutes, hours or days

35
Q

What is the general mechanism of steroid actions: nongenomic?

A

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

36
Q

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

A

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

37
Q

What are examples of nongenomic effects?

A
  1. The rapid suppression of ACTH release
  2. The inhibition of exocytosis in inflammatory cell types
  3. The strong inhibition of growth hormone release
38
Q

What are disorders of steroidogenesis?

A

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

39
Q

When does Addison’s disease occur?

A

When cortisol levels are too low

40
Q

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

A

Dexamethasone

41
Q

What does long term use of dexamethasone lead to?

A

Side effects like immune suppression

42
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45
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Endocrine System (25 decks)

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