Block 4: Sfm 10/21 - Steroid Hormones

Front 1

What are three examples of animal steroids?

Back 1

Sterols (cholesterol)
Bile acids
Steroir Hormones

Front 2

Where are most steroid hormones derived from?

Back 2

Cholesterol

Front 3

What is the typical structure of a steroid?

Back 3

Fused Ring: 6-6-6-5

Front 4

Back 4

Front 5

What does androstane give rise to?

Back 5

Androgens

Front 6

What does pregnane give rise to?

Back 6

Progesterone

Front 7

What does estrane give rise to?

Back 7

Estrogens

Front 8

What is the action of 5-a-reductase?

Back 8

Reduces 5-C double bond in testosterone

Creates 5a-dihydrotestosterone (ACTIVE ANDROGEN)

Front 9

Where in the body is cholesterol synthesized?

Back 9

All tissues

Particularly high in liver, adrenal cortex, gonads, placenta

Front 10

Provide the basic pathway for steroid synthesis. List all enzymes necessary. List rate limiting step.

Back 10

AcCoa + NADH + ATP-->HMGCoA
via HMG CoA Synthase

HMG CoA --> Mevalonate
via HMG CoA Reducatse
THIS IS RLS!
-->
-->
Cholesterol
-->
-->
Steroid

Front 11

What are the controls on HMG CoA Reductase?

Back 11

Genetic level control: When low [sterol], increased transcription of gene

Activity level control: via phosphorylation

Front 12

True/False: Cholesterol is the precursors for all steroid hormones.

Back 12

False; exception is vitamin D

Front 13

Can cholesterol be metabolized?

Back 13

No, it cannot. It is excreted in feces as bile salts and bile acids.

Front 14

Describe the localization of steroid hormone synthesis.

Back 14

Cholesterol synthesized in sER and cytoplasm

Enters mitochondria for side-chain cleavage (via p450 SCC enzyme)

Leaves mitochondria as pregnenolone

-Enters SER and leaves cell as sex steroid (gonads)
OR
-Enters SER, then mito, and leaves cell as glucocorticoids or mineralocorticoids (adrenal cortex)

Front 15

What is sER content like in steroid secreting cells?

Back 15

Steroid secreting cells have ABUNDANT sER

Front 16

What is the reaction catalyzed by cytochrome P450?

Back 16

R + O2 + NADPH + H+
--->
R-OH + H2O + NADP+

(insertion of an OH group onto an R group and reduction of other O to Water)

Front 17

How does cholesterol become cortisol/aldosterone?

Back 17

Cholesterol-->Progesterone
via P450 scc

Progesterone --> Cortisol/aldosterone via P450c 17, 21, 11; 21, 11, 18 respectively

Front 18

How does cholesterol become estrone?

Back 18

Cholesterol-->Progesterone
via P450 scc

Progesterone --> Androstenedione
via P450 c17

Androstenedione-->Estrone
via P450 aromatase

Front 19

How does cholesterol become estradiol?

Back 19

Cholesterol-->Progesterone
via P450 scc

Progesterone --> Androstenedione
via P450 c17

Androstenedione-->Testosterone
Via (unlisted)

Testosterone-->Estradiol
via P450 aromatase

Front 20

What hormone influences the production of cortisol and aldosterone? How?

Back 20

ACTH regulates P450 enzymes

Front 21

What hormone influences the production of estrone and estradiol? How?

Back 21

LH regulates P450 aromatase

Front 22

What is the role of StAR protein? What step in cholesterol synthesis is it required for?

Back 22

Steroid Acute Regulatory Protein: facilitates transfer of cholesterol across both outer and inner mitochondrial membranes

Required for SCC; p450 scc is in inner mitochondria--where metabolism to pregnenolone

Front 23

What would a mutation in StAR lead to? Clinical manifestations?

Back 23

Lipoidal Congential Adrenal Hyperplasia

Genetic loss of steroidogenesis
Cellular damage from accumulated choelsterol
No steroid hormones can be synthesized

ALL individuals are PHENOTYPIC females with severe salt-losing (absence of androgen)

Front 24

What are the clinical manifestations of Smith-Lemli-Opitz Syndrome? How does this disease come about?

Back 24

Mental retardation, AMBIGUOUS GENITALIA (can't produce andorgens) in males, low circulating cholesterol

Defect/Deficit of C7-Reductase: req'd for 7-dehydrocholesterol-->cholesterol

(very upstream)

Front 25

What are the clinical manifestations of Congenital Adrenal Hyperplasia? Cause?

Back 25

Virilization of females (formation of male genitalia) because of excess androgen production, salt-wasting

Tx: glucocorticoid and mineralocorticoid replacement

Cause:

Defect/deficit in C21-hydroxylase; req'd for Progesterone --> cortisol/aldosterone

produce excess androgens!

Front 26

What are the clinical manifestations of a 5a-reductase deficiency?

Back 26

Undervirilized males, virilize at puberty

May have blind vaginal pouch--testes suppress Mullerian derivatives

Remember: 5a-reductase required for testosterone to act on target tissues

Front 27

What determines the biological actions of steroid hormones?

Back 27

Specificity and tissue localization of steroid hormone receptors

Front 28

Explain how steroid hormone receptors interact with heat shock protein, coactivators, and DNA binding elements.

Back 28

Steroid binds receptor, induces conformational change and phosphorylation

HSP released from receptor

Steroid-bound receptors dimerize

Dimer binds Steroid Response Coactivator (SRC; the coactivator)

SRC-dimer binds DNA, begins transcription

Front 29

What are the clinical manifestations of complete androgen insensitivity? Cause?

Back 29

AKA Testicular Feminization

Cause: Mutation in Androgen Receptor Gene

Breast development at pubrerty, absence of menstrual flow (amenorrhea), scant or abscent pubic/axillary hair

Genitalia: Female with blind vaginal pouch

Wolffian derivatives usually absent

Mullerian derivates usually absent or vestigial

Gonads: testes

Front 30

If testosterone is normally at a concentration that nearly saturates the androgen receptors in target tissues, how do anabolic steroids increase muscle mass?

Back 30

Two theories:

1) Fully saturating would fully activate androgen receptors

2) Inhibiting glucocorticoid receptor with anabolic steroids; cortisol binds these receptors and stimulates protein degradation