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Endo Repro Midterm > Steroid Biosynthesis > Flashcards

Steroid Biosynthesis Flashcards

1
Q

general aspects of steroid hormones

LO1

A

signaling molecules that alter gene transcription

  • bind to intracellular receptors (transcription factor)
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2
Q

Types of Steroid Hormones (5)

A
  1. Progesterone
  2. Aldosterone
  3. Cortisol
  4. Testosterone
  5. Estradiol
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3
Q

Progesterone

  • where it is synthesized
  • distributed where
  • function
  • binds to and activates
A

21 carbon

gestation- supportive hormone

synthesized in adrenal gland, ovaries, and testes

distributed to uterus

fxn: mediates implantation and maintenance of pregnancy

binds to and activates progesterone receptors

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4
Q

Aldosterone

  • where it is synthesized
  • distributed where
  • function
  • *- binds to and activates
A

21 carbon
mineralcorticoid that increases Na+ and water retention and raises blood pressure

synthesized in adrenal glands

distributed to kidney tubules, colon, and parotid glands

fxn: increase Na/h20 retention, K excretion and blood pressure

binds to and activates mineralcorticoid receptors

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5
Q

Cortisol

  • where it is synthesized
  • distributed where
  • function
  • *-binds to and activates
A

21 carbon
glucocorticoid “stress” hormone that increases gluconeogenesis and blood pressure and has inflammatory effects

synthesized in adrenal glands

distributed to many organs and tissues

increase BP and Na uptake in kidney

mediates response to stress

***binds to and activates Glucocorticoid receptors

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6
Q

Estrogen

  • where it is synthesized
  • distributed where
  • function
  • binds to and activates
A

synthesized in ovaries, placenta, and adipose tissue

distributed to primary and secondary reproductive organs

mediates feminization, estrous cycle

binds and activates ERa

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7
Q

Androgen

  • where it is synthesized
  • distributed where
  • function
  • *-binds to and activates
A

synthesized in adrenal glands, ovaries, and testes

distributed to primary and secondary reproductive organs

mediates spematogenesis, male, bone maturation

binds to and activates androgen receptor

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8
Q

Short Term response to stress by adrenal glands

  • hormone
  • characteristics
A

Catecholamines

  1. increase HR
  2. increase BP
  3. liver converts glycogen to glucose and release glucose to blood
  4. bronchiole dilation
  5. increase metabolic rate
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9
Q

Long Term response to stress by adrenal glands

  • hormone
  • characteristics
A

Mineralcorticoids and Glucocorticoids

  1. retention to na and h2o by kidneys
  2. increase blood volume and BP
  3. protein and fats converted to glucose or broken down for energy
  4. increased blood sugar
  5. suppression of immune system
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10
Q

Where are steroid hormones derived from?

-enzyme

A

Cholesterol

desmolase

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11
Q

Steroid hormone synthesis
-pathway

LO2

A

cholesterol-> pregnenolone (via desmolase)-> progesterone -> corticosteroids and sex hormones

corticosteroid -> aldosterone and cortisol

sex hormones -> testosterone and estradiol

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12
Q

Progesterone and Pregnancy relationship

A

progesterone supports gestation and embryogenesis

- maintenance of menstrual cycle

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13
Q

Glucocorticoid and infant respiratory distress syndrome relationship
-treatment

A

glucocorticoid alters lung structure by stimulating surfactant production => allows air to expand in normal infants

if not glucocorticoid, leads to IRDS
- tx: give mom glucocorticoid (betamethasome, dexamethasone)

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14
Q

Desmolase

  • nickname
  • location
  • function and regulation
A

cholesterol -> pregnenolone

found in all steroid producing tissues (adrenal, testes, ovary, placenta)

catalyzes rate limiting step

**positively regulated by ACTH

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15
Q

Biochemical Actions of ACTH

  • short term
  • long term
A

Short term actions

  • stimulate lipoprotein uptake into cortical cells
  • increase bioavailability of cholesterol in adrenal cortex

Long term

  • stimulation of transcription of genes coding for steroidgenic enzymes
    • P450scc- catalyzes first step of steroidogenesis (cleavage of side-chain cholesterol)
    • steroid 11B hydroxylase
  • associated electron transfer protein
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16
Q

ACTH and Cancer relationship

A

Normal:
ACTH-> AC-> cAMP-> PKA-> cell proliferation

Tumor cell
constitutively active PKA -> cell proliferation-> cortisol production

17
Q

Congenital Adrenal Hyperplasia

- symptoms

A

hirsutism: excessive body hair

  • oligomenorrhea- infrequent menstruation
  • infertility
  • HLA presentation
  • excess cortisol
18
Q

Congenital Adrenal Hyperplasia

  • classical
  • non classical
A

Classical

  • salt wasting: dehydration, vomit, diarrhea
  • ambiguous genitelia

Nonclassical

  • milder than classical
  • androgen excess+> precocious puberty
  • asymptomatic
19
Q

Adrenal Hyperplasia

- Treatment

A

carefully monitored hormone replacement therapy

20
Q

Congenital Adrenal Hyperplasia

- mutation

A

90-95% involves genes for 21 hydroxylase

5% involves 11B- hydroxylase

21
Q

Defect in steroid hormone syntheses

A
  • **1. excess androgen production
  • **2. 17a hydrocy progesteron accumulation
    3. mutant 11b hydroxylase
    4. corticosterone precursor buildup
22
Q

Hypertension in CAH

A

11 deoxycorticosterone

  • accumulates abnormally
  • constitutive mineralocorticoid
  • receptor (MR) agonist
  • dysregulated salt and water balance
  • promotes Na+ and water retention
  • lowers plasma K concentration
23
Q

Steroid hormone effects with 11B deficiency

A

only 11 deoxycoricosterone and 11 deoztcortisol levels would increase due to this enzyme

11 deoxycorticosterone has much higher affinity for MR to produce HTM

increased Na absorption in kidney => HTN
=> increased aldosterone

24
Q

Congenital Adrenal deficiency

  • hormone
  • effects (4)
A

21 a hydroxylase deficiency

  • reduced cortisol synthesis
  • hyperplasia of adrenal cortex
  • increase ACTH level

hormone accumulate abnormally in adrenal cortex, blood

  • increase progesteron
  • increase 17a hydroxypregnenolone
  • increase 17a- hydroxyprogesterons

salt wasting
- lack of aldosterone=> high rate of sodium loss in urine

25
Q

Steroid hormone blood transporter proteins (2)

- organ

A
  1. corticosteroid binding globulin
    a. glycosylated globin protein
    b. serine-protease- inhibitor family
    c. transport/release of 80-90% of glucocorticoid hormones and progesteron
  2. Sex steroid binding globulin
    a. transport/release of testosterone, digydrotestosterone and estradiol
    b. albumin binds a little bit
    c. partially saturated in women
    d. fully saturated by tesosterone in men

** both cbg and shbg are made in liver

26
Q

Renin Angiotensin Aldosterone System (2)

-organ

A

SAME AS STEROIF HORMONE BLOOD TRANSPORTER PROTEIN

  1. corticosteroid binding globulin
    a. glycosylated globin protein
    b. serine-protease- inhibitor family
    c. transport/release of 80-90% of glucocorticoid hormones and progesteron
  2. Sex steroid binding globulin
    a. transport/release of testosterone, digydrotestosterone and estradiol
    b. albumin binds a little bit
    c. partially saturated in women
    d. fully saturated by tesosterone in men

**both cbg and shbg are made in liver

27
Q

What is the most importatnt biochemical intermediate for steroid biosynthesis?

A

PREGNENOLONE

  • used as substrate to produce other hormones (progesterone, aldosterone, cortisol, testosterone, estradiol)
28
Q

Rare forms of CAH are caused by

A

*** CYP17A1 (17a hydroxylase/ 17,20 lyase)

29
Q

what converts progesterone to testosterone?

A

17,20 lyase

30
Q

isolated 17,20 lyase deficiency (ILD)

A

rare autosomal recessive endocrine disorder

loss of 17,20 lyase activity

impaired production of androgen and estrogen sex steroids

31
Q

Regulation of steroid hormone synthesis

  • stimulatory factor
  • inhibitory factor
  • hormones

LO3

A

Stimulating factors

  1. ACTH
  2. FSH

Inhibitory factor

  1. progesterone
  2. testosterone

Hormones

  1. GnRH
  2. FSH
  3. LH
32
Q

Vitamin D synthesis

  • pathway

LO4

A

cholecalciferol (D3) (in skin or intestine)-> 25-hydroxycholecaliferol in liver (via CYP2R1)-> 1,25 dihydroxycholecalciferil in kidey via 1a-hydroxylase

33
Q

How do we obtain cholecalciferol (D3)?

A
  1. through diet
    - ergocaliferol (D2) absorved in intestine
  2. Through skin
    - converted from 7- dehydrocholesterol in skin cia UV rays
34
Q

IMPORTANT note in Vitamind D production

A

25 hydroxycalciferol is formed exclusively in LIVEr by 25- hydroxylase enzyme encoded by CYP2R1 gene

Endo Repro Midterm (12 decks)

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