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Biochem II > Exam 2 Androgen and Estrogen Signaling > Flashcards

Exam 2 Androgen and Estrogen Signaling Flashcards

1
Q

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

A

Androgen

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2
Q

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

A

Estrogen

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3
Q

Testosterone is synthesized via ____ hydroxylation in the ____ cells

A

17 hydroxylation in the Leydig cells

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4
Q

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

A

human chorionic gonadotropin

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5
Q

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

A

250 ng/dL

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6
Q

At birth, testosterone is stimulated by _______ _______ ______

A

Maternal luteinizing hormone

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7
Q

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

A

500-700 ng/dL in men

30-50 ng/dL in women

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8
Q

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

A

Luteinizing hormone

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9
Q

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

A

DHT and Estradiol

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10
Q

Why is testosterone converted to these two molecules?

A

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

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11
Q

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

A

5 alpha reductase

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12
Q

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

A

CYP19 (aromatase)

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13
Q

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

A

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

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14
Q

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

A

Shorter = more active

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15
Q

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

A

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

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16
Q

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

A

CYP17 hydroxylase

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17
Q

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

A

5-alpha reductase

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18
Q

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

A

Alpha and beta isoforms

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19
Q

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

A

Differential promoters

Alternative splicing

20
Q

Estrogen receptors modulate approximately how many genes?

A

50-100

21
Q

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

A

A/B domain

22
Q

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

A

Beta

23
Q

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

A

C domain

24
Q

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

A

D domain

25
Q

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

A

E and F domain

26
Q

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

A

ER beta

27
Q

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

A

ER alpha

28
Q

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

A

beta inhibits alpha

29
Q

What is nongenomic estrogen signaling?

A

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

30
Q

Estrogenic activity is influenced by what three factors?

A
  1. *** Distribution of cofactors and corepressors of ER complex within the tissue
  2. Type of estrogen
  3. Subtype of estrogen receptor within tissue
31
Q

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

A

ER+ breast cancers

32
Q

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

A

Use ER alpha specific antibodies

Doesn’t detect ER beta

33
Q

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

A
  1. Specific hydrogen bonds

2. Complementarity of the binding cavity to the hormone’s nonpolar character

34
Q

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?

A

Helix 12

35
Q

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

A

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

36
Q

Testosterone secretion is stimulated by what hormone in utero?

A

Human chorionic gonadotropic

37
Q

Testosterone secretions is stimulated by what hormone after birth?

A

Luteinizing hormone

38
Q

What androgen/estrogen is responsible for wolffian development?

A

Testosterone

39
Q

What androgen/estrogen is responsible for external genitalia?

A

DHT

40
Q

What androgen/estrogen is responsible for muscle mass?

A

Testosterone

41
Q

What are the two major factors for androgen receptor signaling?

A
  1. DHT as a higher potency ligand

2. Cell-specific coregulators

42
Q

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

A

Upregulation of gene transcription

43
Q

Which hormones cause production of estrogens in premenopausal women?

A

Gonadotropins such as FSH and LG

44
Q

Which hormones cause production of estrogen in postmenopausal women?

A

Adrenocorticotropic hormone (ACTH)

45
Q

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

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

Biochem II (7 decks)

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