L72: Steroids

Question 1

What is a hormone?

Answer 1

1) Signaling molecule
2) Secreted by specialized cells in response to a stimulus
3) Act on another tissue ad is transported through the blood

Question 2

What are the steroids hormones?

Answer 2

1) Cortisol
2) Aldosterone
3) Testosterone
4) Estrogen/ Estradiol

Question 3

How many C does cortisol have?

Answer 3

21

Question 4

How many C does aldosterone have?

Answer 4

21

Question 5

Which steroid hormone have 21C?

Answer 5

Aldosterone

Cortisol

Question 6

Which steroid hormone have 19C?

Answer 6

Testosterone

Question 7

Which steroid hormone have 18C?

Answer 7

Estrogen

Question 8

Where is cortisol secreted?

Answer 8

Adrenal Glang

Question 9

Where is aldosterone secreted?

Answer 9

Adrenal Gland

Question 10

Where is testosterone secreted?

Answer 10

Testes

Low amount by adrenal gland

Question 11

Where is estrogen secreted

Answer 11

Ovaries

Low amount by adrenal gland

Question 12

Where does cortisol act?

Answer 12

Liver- activates gluconeogenesis enzymes

Question 13

Where does aldosterone act?

Answer 13

Kidney

1) increase Na+ reabsorption
2) increase K+ secretion into the urine

Question 14

Where does testosterone act?

Answer 14

Increasing muscle mass

Question 15

Where does estrogen act?

Answer 15

Increase uterine mass

Also important for maintaining healthy bones

Question 16

What happens if we have a decrease in the function of the adrenal gland

Answer 16

1) Cortisol decrease (Addison Disease)
- -> No stimulation of gluconeogenesis
2) Aldosterone decrease
- > BP problems bc of Na+ and K+ not absorbed/ secreted

Question 17

What is the general st of the steroids hormone?

Answer 17

3 6 membered rings

1 5 membered ring

Question 18

Cortisol structure

Answer 18

OH on C21
C11
C17

Question 19

Which OH on cortisol is important for gluconeogenic activity?

Answer 19

C21

C17

Question 20

Structure of aldosterone

Answer 20

OH on C21 and C11
Aldehyde on C18

Remember: ALDosterone
ALDehyle!!

Question 21

Which is the only steroid with a C18 aldehyde?

Answer 21

Aldosterone

Question 22

Structure of testosterone

Answer 22

OH on C17

double bond between C4 and C5 in ring A

Question 23

Structure of Estrogen

Answer 23

OH on C17

phenol ring in ring A

Question 24

Difference in structure between Testostrone and Estrogen

Answer 24

T: db between C4 and C5 in ring A
E: phenol ring A

Question 25

How is the secretion of the cortisol made?

Answer 25

1) Stress in then rain
2) Message to HYPOTHALAMUS
–> Corticotropic Releasing Hormone CRJ
3) CRH goes to pituitary
–> AdrenoCorticoTropic Hormone
ACTH
4) ACTH goes to adrenal gland which activates Desmolase E (cuts the side chains of cholesterol) and hydrolyses to make cortisol

Question 26

How does cortisol inhibit the synthesis of more cortisol?

Answer 26

It goes to pituitary and inhibits the synthesis of ACTH
Inhibition of ACTH would inhibit CRH
–> Feedback inhibition

Question 27

What happens in Addison’s Disease?

Answer 27

Adrenal gland hypofunctioning

• -> Cortisol not made
• -> No feedback inhibition
• -> Too much ACTH made
• -> ACTH has the same first 13 aa as MSH (Melanocyte Stimulating Hormone)
• -> ACTH binds on MSH receptor
• -> Darkening of the skin- starts in gum

Question 28

How is the general scheme for making steroids?

Answer 28

1) desmolase: cleaves the side chain of cholesterol

2) Hydroxylase adds OH

Question 29

Which Hydroxylase needed to make cortisol?

Answer 29

21, 11 and 17

Question 30

Which Hydroxylase needed to make aldosterone

Answer 30

21, 11 and 18 (then dehydrogenase)

Question 31

Which Hydroxylase needed to make

Answer 31

17

Question 32

What are the characteristics of steroids?

Answer 32

11) Water insoluble –> need to be bound to plasma protein to circulate in the blood
2) Can act at

Question 33

How is cortisol transported in the blood?

Answer 33

Through Cortiso steroid Binding Globulin (CBG)

Question 34

What happens if CBG lacks?

Answer 34

Cortisol cannot get to liver

But we would not expect to see the same effect as in addison bc cortisol in mad it just cannot circulate

Question 35

How are Testosterone and Estradiol transported?

Answer 35

Sex Hormone Binding Globulin

Question 36

How do steroid hormones work?

Answer 36

1) Free diffusion into cells
2) Bind to receptor intracellularly
3) Coactivator binds to Hormone binding site on receptor
4) Hormone- Receptor get into the nucleus
5) DNA binding site of receptor w/ Zn fingers binds to certain genes and activate transcription

Question 37

How do coactivators work?

Answer 37

1) Histone acetyl transferase
2) Activate RNA Pol II

–> Activation of Transcription

Question 38

What makes the specificity of the hormone receptor

Answer 38

Zn fingers = DNA Binding site have specific seq comp to regulator of target genes

Question 39

Relationship of Estrogen to Breast cancer

Answer 39

Some Tumors are Estrogen Receptor +

–> If we decrease estrogen, the tumor will shrink

Question 40

How can we treat Breast cancer targeting estrogen?

Answer 40

1) Antibody against estrogen= Tamoxifen (endocrine ablative therapy)
- -> Problem for bone

2) Aromatase Inhibitors= Letrozole -> inhibit the E making estrogen
- -> Might cause bone problem

Question 41

What should be consider in endocrine ablative therapy for breast cancer?

Answer 41

Osteroporosis

Question 42

Difference between peptide and steroid hormones?

Answer 42

Peptide extracellular receptor
Steroid: Intracellular receptor bc it is lipophilic and can cross plasma

Peptide: Acts within minutes bc it activates other enzymes
Steroid: Acts within hours bc it activate transcription

Peptide: Might activate cAMP
Steroids: Does not activate cAMP

Question 43

At what point does the receptor move from cytoplasm to nucleus?

Answer 43

Only after binding to the hormone