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Endocrine - MSI Spring > Steroid Biosynthesis > Flashcards

Steroid Biosynthesis Flashcards

1
Q

Describe endocrine signaling

A

long distance signaling through bloodstream
freely diffusible
long lasting

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2
Q

What is the site of synthesis, distribution and effects of progesterone?

A

synthesized in adrenal glands, ovaries and testes
Distributed to uterus
mediates implantation and maintenance of pregnancy

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3
Q

What is the site of synthesis, distribution and effects of glucocorticoids?

A

(e.g. cortisol)
Synthesized in adrenal glands
distributed to large # of tissues and organs
increases blood pressure and Na up-take in kidneys
affect brain development
Mediates response to stress by increasing protein catabolism and gluconeogenesis (fight or flight) and reducing inflammation (suppress immune)

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4
Q

What is the site of synthesis, distribution and effects of aldosterone and other mineralocorticoids?

A

synthesized in adrenal glands
distributed to kidney tubules, colon, and parotid gland
Increases Na/H2O retention, K excretion and BP

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5
Q

What is the site of synthesis, distribution and effects of estrogens?

A

Synthesized in ovaries, placenta, and adipose tissue
Distributed to primary and secondary reproductive organs
mediates feminization, estrous cycle, and inhibits testosterone synthesis

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6
Q

What is the site of synthesis, distribution and effects of androgens (testosterone, DHEA)?

A

Synthesized in adrenal glands, ovaries, and testes (major)
distributed to primary and secondary reproductive organs and muscle
mediates spermatogenesis, secondary male characteristics, bone maturation, and virilization

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7
Q

Endocrine cell signaling occurs with ________.

A

ligands

*can be proteins, small peptides, aa derivatives, hydrophobic molecules even gases like NO

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8
Q

What are the main categories of signaling molecules?

A

Small lipophilic molecules: steroid hormones

Water soluble molecules - hydrophilic

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9
Q

What are the lypophilic signaling molecules Dr. Theisen wants us to know?

A

Steroid hormones: progesterone, estradiol, testosterone, cortisol, aldosterone, Vit D

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10
Q

What are steroids synthesized from?

A

cholesterol in smooth ER of adrenal cortex, ovaries, and testes

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11
Q

What is the affinity of signaling receptors?

A

high affinity - bind to ligands with great specificity (concentration of ligand in bloodstream is low)

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12
Q

What are the general two types of receptors?

A

Intracellular receptor: small hydrophobic/steroid receptor - alters gene expression in nucleus

(majority) Cell surface receptors: cytoplasmic domain initiates signal by change in confirmation

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13
Q

Steroid signaling is a fast or slow response?

A

slow because it takes longer to interact with gene expression

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14
Q

What are the domains commonly found with intracellular receptors?

A

Transcription-activating domain
DNA-binding domain
Ligand-binding domain

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15
Q

Where do tissues that synthesize steroids obtain cholesterol from?

A

Circulating LDL, from de novo synthesis from acetyl CoA, or from cholesterol esters stored in cytoplasmic lipid droplets (fatty acids)

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16
Q

How is Vit D synthesized from acetyl CoA?

A

3 acetyl CoA form IPP
6 IPP come together - 30 carbons
modified to become 27 carbon Vit D

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17
Q

What is the rate limiting step of steroid hormone synthesis?

A

Desmolase: incorporates a carbonyl group (C=O) on the D ring of cholesterol and cleaves off a six-carbon piece of its side chain to form pregnenolone

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18
Q

What does pregnenolone act as?

A

a modulator of neurotransmitter signaling in the brain w/o being converted to other steroids

Effects the NMDA glutamate receptor (memory and learning)

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19
Q

What must pregnenolone by converted to first for synthesis of other progestrogens?

A

progesterone

by 17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase

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20
Q

What are the 4 types of progestrogens?

A

mineralocorticoids, glucocorticoids, estrgens and androgens

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21
Q

________ have affinity for mineralocorticoid receptors and are ____ times more concentrated than mineralocorticoids

A

glucocorticoids

100

22
Q

What are the synthetic forms of anabolic steroids used for?

A

PEGs - performing enhancing drugs

affecting natural testosterone signaling pathways

23
Q

the arm of Androgens and estrogens pathway synthesis in the adrenal cortex is the ______ pathway

A

minor

24
Q

The mineralocorticoid and glucocorticoid pathways are exclusive in what tissue? What enzyme would you expect to find exclusively with these pathways?

A

adrenal cortex

21-alpha hydroxylase

25
Q

Aldosterone (a mineralocorticoid) is converted from progesterone in what tissue?

A

Zona glomerulosa - adrenal cortex

26
Q

Progesterone is converted to cortisol (a glucocorticoid) in what tissue?

A

zona fasciculata - adrenal cortex

27
Q

Progesterone is converted to estradiol (an estrogen) in what tissue?

A

in ovaries from testosterone!

minor amount in adrenal cortex

28
Q

Progesterone is converted to testosterone (an androgen) in what tissue?

A

in testes
also dihydrotestosterone (more potent) formed
Minor amount in adrenal cortex

29
Q

Where is desmolase only found?

A

in tissues that produce steroid hormones (gonads and adrenal cortex)

30
Q

What is the expression and activity of desmolase stimulated by?

A

peptide hormones

  1. ACTH: activates expression
  2. LH: increases activity
  3. FSH: activates aromatase
31
Q

What happens if there is a defect in 21-hydroxylase?

A

salt wasting (hyponatremia) and hypotension due to decreased porduction of aldosterone, and hypoglycemia due to decreased production of cortisol

In females: cuases virilism (dev of male secondary characteristics) due to increased flow of intermediates into adrenal androgens

32
Q

Describe the deficiency of 17-a-hydroxylase

A

rare
causes loss of cortisol as well as sex steroids
Decrease in cortisol compensated for by increased production of corticosterone

33
Q

Describe what occurs with defect in 11-beta-hydroxylase

A

causes hypertension due to accumulation of 11-decoxycorticosterone, which has mineralocorticoid activity

34
Q

Reduced levels of aldosterone =

Excessive levels =

A

Loss of too much salt

Conn syndrome - increase blood volume, hypertension

35
Q

What is cortisol also known as?

A

hydrocortisone

36
Q

Elevated levels of cortisol =

A

Cushing syndrome, a condition marked by the accumulation of fat on face and trunk

Pituitary or adrenal tumors or chronic administration of corticosteroids

37
Q

Cortisol has an important affect on ____ feedback inhibition

A

ACTH

38
Q

How does cortisol cause immunosuppresion?

A

inhibits both cellular and humoral immune response
induce production of i-kBa inhibitory protein
NF-kB sequestered: no synthesis of many cytokines

Promotes T cell apoptosis - decreased IL-2
Inhibition of donal expansion of B cells

39
Q

Must metabolize cortisol to cortisone through action of _________

A

11 beta-hydroxysteroid dehydrogenase

40
Q

Mineral corticoid target tissues such as the kidneys, colon, and parotid gland contain a receptor that has equal affinity for ______

A

both mineralo- and glucocorticoids

41
Q

What food can inhibit 11b-hydroxysteroid dehydrogenase? what could this lead to?

A

real licorice

hypertension due to salt retention

42
Q

(cortisol/cortisone) has much lower affinity for mineralocorticoids

A

cortisone

-dehydroxylated form

43
Q

How is the androgenic potency of testosterone amplified?

A

by its conversion to dihydrotestosterone DHT mediated by enzyme 5 alpha -reductase

*DHT has much higher affinity than testosterone for androgen receptor

44
Q

What is finasteride? What is it used for?

A

An inhibitor of 5 alpha - reductase
prevents potentiation

Used to treat benign prostatic hyperplasia
Treat male pattern baldness - caused by DHT in scalp

45
Q

What is the active form of Vitamin D?

A

Calcitriol (1,25 - dihydroxycholecalciferol)

Technically not classified as a steroid
Alters expression of target genes containing VDRE seq

46
Q

What are the inactive forms of Vitamin D? Where are they derived from?

A 
Vitamin D2 (ergocalcifrol) and Vitamin D3 (cholecalciferol)
Found in liver, eggs, fish, plants, and vitamin D fortified foods like milk and cereal

VD3 also produced in skin with sunlight

47
Q

How is the inactive form of Vit D (cholecalciferol D3) produced?

A

In skin from photochemical cleavage of B ring of 7-dehydrocholesterol (via UV irradiation in the skin)

In intestinal cells from ergocalciferol (Vit D2)

48
Q

What converts inactive Vit D into 25-hydroxycholecalciferol? where does this take place?

A

25-hydroxylase

Liver

49
Q

What converts 25-hydroxycholecalciferol into 1,25 - dihydroxycholecalciferol? Where does this take place?

A

1-alpha hydroxylase

Kidney (proximal tubules) when PTH is present and low PO4

Inhibited by calcitriol

50
Q

What does calcitriol stimulate in the body? What positively regulates and what inhibits this process?

A

intestinal cells to increase absorption of Ca and PO4
Increase reabsorption of Ca by kidneys
Promote resorption of Ca from bone
Elevate blood Ca and PO4 levels

+ PTH
- Calcitonin

51
Q

What can cause deficiencies in Vit D?

A

conditions that disrupt the absorption of lipids, inadequate dietary intake and poor functioning of liver and kidneys

Hypoparathyroidism
Lack of sunlight
Leads to brittle bones (ricketts, osteomalacia)
hypocalcamic tetany: low blood calcium

Endocrine - MSI Spring (15 decks)

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