Exam 2 Androgen and Estrogen Signaling

Question 1

(Estrogen / Androgen) signaling is implicated in prostate cancer, prostatic hyperplasia, and male-pattern baldness

Answer 1

Androgen

Question 2

(Estrogen / Androgen) signaling is implicated in breast cancer and ovarian cancers

Answer 2

Estrogen

Question 3

Testosterone is synthesized via ____ hydroxylation in the ____ cells

Answer 3

17 hydroxylation in the Leydig cells

Question 4

First trimester in utero, testosterone is stimulated by ________ ________ _______

Answer 4

human chorionic gonadotropin

Question 5

Second trimester in utero, testosterone reaches a peak level of _____ ng/dL, and then falls off

Answer 5

250 ng/dL

Question 6

At birth, testosterone is stimulated by _______ _______ ______

Answer 6

Maternal luteinizing hormone

Question 7

At puberty, testosterone reaches ____ - _____ ng/dL in men, and _____ - _____ ng/dL in women

Answer 7

500-700 ng/dL in men

30-50 ng/dL in women

Question 8

Which hormone is the main stimulus for testosterone secretion after birth?

Answer 8

Luteinizing hormone

Question 9

Which two potent molecules is testosterone converted to in the body?

Answer 9

DHT and Estradiol

Question 10

Why is testosterone converted to these two molecules?

Answer 10

DHT and Estradiol are more potent than testosterone, for when circulating concentrations of testosterone are insufficient to affect certain tissue types

Question 11

Cells expressing what enzyme can take up testosterone and converted to DHT to bind to the androgen receptor more efficiently?

Answer 11

5 alpha reductase

Question 12

Cells expressing what enzyme cant take up testosterone and convert to estradiol to bind to the estrogen receptor more efficiently?

Answer 12

CYP19 (aromatase)

Question 13

What are the 5 structures present on an androgen receptor, in order from the N –> C terminal?

Answer 13

Glutamine, Proline, Glycine, DNA binding domain, Hormone binding domain

Question 14

Androgen receptors with a (shorter / longer) glutamine chain are more active

Answer 14

Shorter = more active

Question 15

What is the benefit of having coregulators that are cell-specific bind to the androgen receptor?

Answer 15

Allows cell-specific gene regulation due to androgen binding (i.e. effects on hair follicles vs. testicular)
aka don’t have pubes on head

Question 16

Deficiencies of androgens are commonly due to deficiency of which enzyme?

Answer 16

CYP17 hydroxylase

Question 17

Deficiency in this enzyme results in failure of external genitalia to develop, due to the lack of DHT, but internal genitalia can develop

Answer 17

5-alpha reductase

Question 18

Estrogen receptors exist in the ____ and ____ isoforms that form heterodimers

Answer 18

Alpha and beta isoforms

Question 19

What are two reasons why multiple isoforms of estrogen receptors occur?

Answer 19

Differential promoters

Alternative splicing

Question 20

Estrogen receptors modulate approximately how many genes?

Answer 20

50-100

Question 21

Domain of ER where the NH2-terminal contains and activation function-1 segment that can activate transcription independent of ligand binding

Answer 21

A/B domain

Question 22

Which isoform of estrogen receptor does not contain (AF-1)?

Answer 22

Beta

Question 23

Domain of ER that is the DNA binding domain that is high conserved and interacts with estrogen response element (ERE)

Answer 23

C domain

Question 24

“Hinge region” domain of ER that has the nuclear localization signal

Answer 24

D domain

Question 25

Ligand binding domain of ER that is mediated by AF-2?

Answer 25

E and F domain

Question 26

Isoform of ER that is found in the kidney, intestinal mucosa, lung, bone, brain, prostate, and vasculature

Answer 26

ER beta

Question 27

Isoform of ER that is found primarily in the endometrium, ovary, mammary gland, hypothalamus, endothelial cells, and vascular smooth muscle

Answer 27

ER alpha

Question 28

In many cases, ER _____ inhibits ER _____ mediated transcriptional activation (has pro-apoptotic and anti-proliferative)

Answer 28

beta inhibits alpha

Question 29

What is nongenomic estrogen signaling?

Answer 29

ER binds to growth factors and various tyrosine kinase receptors (IGF-IR, EGFR, and HER2). Estradiol especially activates these pathways, and promotes cell proliferation and survival. These pathways are upregulated in various cancers

Question 30

Estrogenic activity is influenced by what three factors?

Answer 30

1. *** Distribution of cofactors and corepressors of ER complex within the tissue 2. Type of estrogen 3. Subtype of estrogen receptor within tissue

Question 31

Which type of ER (+ or -) responds to estrogen receptor modulators in breast cancers?

Answer 31

ER+ breast cancers

Question 32

Current procedures for treating breast cancers use ER (alpha or beta) specific antibodies, and does not detect ER (alpha or beta)

Answer 32

Use ER alpha specific antibodies | Doesn't detect ER beta

Question 33

How is hormone recognition achieved when binding 17beta-estradiol to the ligand binding domain? (2)

Answer 33

1. Specific hydrogen bonds | 2. Complementarity of the binding cavity to the hormone's nonpolar character

Question 34

What is the terminal helix in the LBD that folds across the formed pocket, stabilizes ligand-receptor interaction, and promotes a conformation conducive for coactivator association?

Answer 34

Helix 12

Question 35

What happens to helix 12 when in the presence of an antagonist?

Answer 35

Helix 12 positions itself in the region typically occupied by the coactivator, which blocks the activation of the receptor

Question 36

Testosterone secretion is stimulated by what hormone in utero?

Answer 36

Human chorionic gonadotropic

Question 37

Testosterone secretions is stimulated by what hormone after birth?

Answer 37

Luteinizing hormone

Question 38

What androgen/estrogen is responsible for wolffian development?

Answer 38

Testosterone

Question 39

What androgen/estrogen is responsible for external genitalia?

Answer 39

DHT

Question 40

What androgen/estrogen is responsible for muscle mass?

Answer 40

Testosterone

Question 41

What are the two major factors for androgen receptor signaling?

Answer 41

1. DHT as a higher potency ligand | 2. Cell-specific coregulators

Question 42

Binding of ERE leads to (up / down) regulation of gene transcription?

Answer 42

Upregulation of gene transcription

Question 43

Which hormones cause production of estrogens in premenopausal women?

Answer 43

Gonadotropins such as FSH and LG

Question 44

Which hormones cause production of estrogen in postmenopausal women?

Answer 44

Adrenocorticotropic hormone (ACTH)

Question 45

Put the following estrogens in order of most potent to least potent (Estrone, Estriol, Estradiol)

Answer 45

1. Estradiol most potent 2. Estrone 3. Estriol least potent