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Exam 3 Steroid Synthesis Flashcards

1
Q

Name androgens

A

testosterone
Dehydroepiandosterone ( DHEA)
Dihydrotestosterone
Androstenedione

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2
Q

name a few estrogens

A

17 b estradiol (18 c estrogen)

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3
Q

hormone that is required for embryo implantation

A

progesterone

  • released from corpus luteum
  • maintains uterine endometrium for implantation
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4
Q

functions of DHEA

A

dehydroepiandosterone

  • weak androgen, converted to its potent form in extra adrenal tissue
  • inhibits G6PDH
  • regulates NAD+ coenzymes
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5
Q

DHEA is a precursor for what??? in ______

A

precursor for estrogen in POSTMENOPAUSAL women

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6
Q

function of aldosterone

A

(secretion of K, absorption of Na)

  • mineralocorticoid
    secreted when version becomes hypovolemic
    raises blood volume and blood pressure by promoting the reabsorption of sodium
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7
Q

function of cortisol

A
  • glucocorticoid
    increases levels of glucose by increasing :
    -gluconeogenesis in liver
    -protein degradation in muscles
  • mobilization of fatty acids from adipose
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8
Q

Which hormones are synthesized in adrenal glands

A

cortisol
aldosterone
DHEA
androstenedione

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9
Q

which hormones are synthesized in gonads

A

17B estradiol
testosterone
DHT (dihydrotestosterone)*
progesterone

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10
Q

what is the role of StAR

A

Steroidogenic acute regulatory protein

- transport protein that transports cholesterol* from cytosol* into mitochondria* (NOT the other way around)

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11
Q

what is the rate limiting step in steroid biosynthesis,

where does it occur

A

cholesterol (c-27) —–> pregnenolone (c-21) + isocaproaldehude (c-6)

aka side chain cleavage of cholesterol
occurs in mitochondria

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12
Q

enzyme responsible for RLS of steroid biosynthesis

A

desmolase (20-22 lyase)

type of p450 hydroxylase

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13
Q

what is the role of 5a reductase

A

responsible for converting testosterone into dihydrotestosterone (much more potent)

located in smooth ER

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14
Q

_____ converts testosterone into estradiol

where is it carried out

A

aromatase

  • p450 hydroxylase
  • in leydig cells

or via DHEA in follicular cells and mammary glands

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15
Q

where is aldosterone

A

Zona Glomerulosa

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16
Q

where is cortisol produced

A

zona fasciculata and zona reticularis of adrenal gland

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17
Q

what are endorphins

A

compounds that bind to morphine receptors*
play a role in pain perception*
secreted from anterior pituitary gland

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18
Q

hormones released by hypothalamus (6)/ function

A

-TRH (Tyrotropin releasing hormone)-
- GnRH (Gonadotropin Releasing Hormone)-
-CRH (corticotropin releasing hormone)
GHRH (growth hormones releasing hormone)
GHR (inhibitory)- somatostatin
PRL- prolactin inhibitor

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19
Q

Function of TRH

A

thyrotropin releasing hormone

- stimulates release of tyrotropin and prolactin

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20
Q

Function of GnRH

A

gonadotropin releasing hormone

-stimulates LH and FSH

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21
Q

function of CRH

A

corticotropin releasing hormone

-stimulates release of ACTH and B-I endorphin

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22
Q

function of GHRH

A

stimulates release of GH

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23
Q

GHR inhibitor

A

somatostatin

- inhibits release of GH, glucagon and gastrin

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24
Q

PRL inhibitor

A

Dopamine— (from median eminence)

- inhibits prolactin release

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25
Q

the most common enzyme in steroid biosynthesis*

A

Desmolase

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26
Q

conversion of cholesterol into pregnelone occurs in_______

A

mitochondria*

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27
Q

What is the second messenger that stimulates the synthesis and secretion of cortisol?

A

Camp

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28
Q

What is the second messenger that stimulates the synthesis and secretion of
aldosterone?

A

Phosphotidylinositol cascade…. IP3 and DAG

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29
Q

Name the second messenger that is produced as a result of atrial natriuretic factor
binding to kidney cells.

A

cGMP- second messenger

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30
Q

Guanylate cyclase catalyzes the formation of ____

A

cGMP

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31
Q

cholesterol esterase catalyzes formation of

A

cholesteroel

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32
Q

hormone that triggers synthesis and secretion of adrenal steroid is

A

ACTH

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33
Q

desmolase catalyses formation of____

A

pregnenonole

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34
Q

CYP is defined as

A

genes that encode for cytochrome P450 enzymes

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35
Q

Conversion of Angiotensin I to angiotensin II is by

A

Angiotensin converting enzyme ACE

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36
Q

in congenital adrenal hyperplasia the enzyme that is deficient is?

A

CYP21A2

-cytochrome P450 steroid 21- hydroxylase

37
Q

adrenal insufficiency causes___

A

addisons disease

38
Q

2 reasons for Cushings syndrome

A
  • prolonged exposure to glucocorticoids caused by usage of cortisol
  • tumors of adrenal cortex
39
Q

Name an adrenal steroid that causes HTN upon its overproduction.

A

minerolocorticoids-

aldosterone

40
Q

Aldosterone antagonist

A

spironolactone

41
Q

name two Ace inhibitors

A

captopril, lisinopril enalapril

42
Q

pregnancy is maintained by continuous secretion of progesterone which is stimulated by ____

43
Q

how is apoptosis stimulated during ovarial cycle?

A

Apoptosis is stimulated during ovarian cycle by the removal of the steroids estradiol and
progesterone.

44
Q

testosterone to estradiol is catalyzed by?

45
Q

hormones that stimulate luteolysis

A

oxytocin and PGF2a

46
Q

human placenta lacks which hydrolase enzyme

47
Q

testicular feminization is the result of?

A

5 alpha reductase

48
Q

cortisol is transported from Adrenal to target tissue by

A

transcortin

49
Q

transcortin binds to**

A

Target tissue of cortisol*

50
Q

testosterone is transported by?

A

TEBP- testosterone estrogen binding protein

51
Q

plasma protein that binds non specifically to steroids

52
Q

2 compounds that inactivate steroids upon conjugation

A
  • Glucouronides
  • sulfates

ex- estradiol inactivated by conjugation with glucoroate

53
Q

receptors for FSH LH gnRH angiotensin II and II are located on

A

plasma membrane

54
Q

receptors for cortisol and aldosterone are located on

A

cell interior

55
Q

receptors for testosterone, estrogen and progesterone are located in

56
Q

what are heat shock proteins

A

Heat shock proteins are cytosolic proteins that occlude the DNA binding region of the cortisol
and aldosterone receptors and cause the receptors to be inactive.

57
Q

Define hormone response element

A

Hormone response element is a region of DNA to which a hormone receptor complex can bind
to and activate transcription.

58
Q

glucocorticoids cause repression of

A

proopiomelanocortin gene

59
Q

the active conformation of a steroid hormone receptor is a???

A

TRIMER

not a dimer

60
Q

Describe the DNA binding domain of hormone receptor.

A

The DNA binding domain of hormone receptors shares 60­95% homology between steroid
receptor classes. They also contain Zn fingers.

61
Q

what are Zn fingers

A

secondary structures in DNA binding domain that facilitate binding to DNA near the transcription initiation complex

62
Q

What are the secretion signals for aldosterone, cortisol, testosterone,
17­beta­estradiol and progesterone respectively?

A 
Aldosterone: Angiotensin II/III
Cortisol: ACTH
Testosterone ­ LH
17­- b-estradiol : FSH
Progesterone:­ LH
63
Q

Name the bone forming and bone resorbing cells. Name some bone antiresorptive
compounds.

A

Osteoblasts (forming), Osteoclasts (resorbing). Antiresorptive compounds include,
bisphosphanates, alendronate (Fosamax), and risedronate (Actonel).

64
Q

Name a catabolic product of estradiol the induces breast cancer.

A

16­hydroxy estrogen (16­OHEN) a side effect of Hormone Replacement Therapy for
osteoporosis.

65
Q

What are the compounds that are being used in hormone replacement therapy (HRT)
treatment?

A

Equine estrogen, medroxy progesterone (progestin).

66
Q

Name the universal sulfonate donor compound.

A

3’­phosphoadenosine 5’­phosphosulfate (PAPS).

67
Q

BASIS of congenital adrenal hyperplasia

A

g​enetic defect decreasing cortisol
production, ACTH production unregulated, thus levels are high. Causes adrenal hyperplasia,
progesterone buildup (increase production of androgens/DHEA/androsteinedione), virilization in
females, precocious sex organ development in prepubertal males, or salt imbalance diseases
due to low aldosterone levels.

68
Q

Addisons

A

­ ​Overall deficiency of adrenal steroids. ACTH levels are high.

Hypoglycemia due to low cortisol. Hypotension due to low mineralcorticoids.

69
Q

Cushings

A

​Prolonged exposure to glucocorticoids (due to anti­inflammatory
use of cortisol or adrenal cortex tumors). Leads to high BSL, and truncal oesity with thin arms
and legs. May also exhibit hypertension.

70
Q

HTN

A 
­​Excessive secretion of mineralcorticoids from adrenal tumors.
Treated with Aldosterone antagonists (spironolactone) 
ACE inhibitors (captopril, lisinopril, enalapril)
71
Q

Osteoporosis

A

​Estrogens induce synthesis of osteoprotegrin, which leads to

osteoblast differentiation. Lack of estrogen can lead to a reduction in bone mass, especially in
post­menopausal women.

72
Q

Testicular feminization

A

​Genetic deficiency in 5­alpha­reductase, which
causes a reduction in DHT (an androgen that promotes the differentiation of male sexual
characteristics. XY with female gentalia (phenotypically, but do not actually have ovaries or
uterus).

73
Q

Describe the role of fetal adrenal and fetal liver with reference steroid metabolism
during pregnancy.

A

Human placenta lacks CP17 (needed to make DHEA which is precursor to Estrogen). The Fetal
adrenal gland converts cholesterol to DHEA, then is transported to the fetal liver forming
16­alpha­hydroxy­DHEA. Aromatization will result in 17­Beta­estradiol.

74
Q

Describe the process of estradiol mediated programmed cell death.

A 
A drop of estradiol and progesterone result in the sloughing of the endometrium (menstration).
Degradative enzymes (proteases, nucleases, and lipases) are stimulated.
75
Q

Describe atrial natriuretic factor (ANF) mediated signaling.

A

ANF comes from heart atrial cells that oppose the actions of angiotensin. Binds to Zona
glomerulosa cell receptors which activates guanylate cyclase leading to the formation of second
messenger cGMP from GTP. cGMP increases aldosterone synthesis and secretion.

76
Q

Key enzymes in steroid metabolism

A

Cholesteryl esterase, Desmolase, Cytochrome P450 hydroxylase enzymes (17­hydroxylase,
21­hydroxylase, etc).

77
Q

mechanism of p450 hydrozyase catalyzed reaction

A

cholesterol side chain cleavage

78
Q

name 4 digestion related endocrine hormones

A

CCK
gastrin
GIP- gastric inhibitory peptide
secretin

79
Q

4 cells that secrete the GIT hormoones

A

duodenal I cells- CCK
Antral G cells- gastrin
Duodenal K cells- GIP
S cells - Secretin

80
Q

name the 2 families of GIT peptide hormones

A

Secretin family of peptides: includes secretin, glucagons, VIP and GIP.
Gastrin family of peptides: includes gastrin and CCK. Identical C­terminal sequences of first of 5
a.a.

81
Q

Function of gastrin

A

stimulate release of HCL from parietal cells of stomach and regulate growth of mucosa

stimulated by food, inhibited by secretin and somatostatin

82
Q

what is the secretion signal for CCK

A

CCK released in response to certain a.a. (tryptophan, phenylalanine), peptides released by
gastric proteolysis, acid pH, lipid and free fatty acids.

83
Q

2 functions of CCK

A

CCK causes contraction of gallbladder to secrete bile acids and it stimulates the secretion of
pancreatic enzymes from the pancreas.

84
Q

The functional part of the hormone, gastrin and CCK resides in the region of the
peptide.

A

Last five a.a. of the C­terminus.

85
Q

name the secretion signal and function of secretin

A

Secretin is released in response to acidification (PH < 5) of the contents of the duodenum.
Secretin works to stimulate the secretion of pancreatic juice rich in bicarbonate.

86
Q

Major hormone that causes NACL secretion is

A

VIP- vasoactive intestinal peptide

87
Q

Guanylin promotes secretion of

88
Q

GIP stimulates secretion of

89
Q

glucose stimulates secretion of?

A

GIP and therefore insulin

Biochem (10 decks)

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