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MD1 Endocrine > Steroid Hormones > Flashcards

Steroid Hormones Flashcards

1
Q

What is the precursor for steroid hormones?

A

Cholesterol

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2
Q

What happens to cholesterol during steroid hormone synthesis?

A

C atoms undergo redox reactions

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3
Q

To what are cytochrome P450 enzymes bound within the cell?

A

Mitochondrial/endoplasmic reticulum membranes

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4
Q

What do cytochrome P450 enzymes contain?

A

Haeme group

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5
Q

What type of reaction are cytochrome P450 enzymes involved in during the synthesis of steroid hormones?

A

Reduction using NADPH
Hydroxylation of C-H bond to C-OH
- For some, coupled with cleavage of C-C bond

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6
Q

What happens in the first step of steroid hormone biosynthesis?

A

Cholesterol side chain cleavage enzyme (cholestero SCC) converts cholesterol > pregnenolone

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7
Q

What is the first intermediate of steroid hormone synthesis?

A

Pregnenolone

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8
Q

What do hydroxysteroid dehydrogenases (HSD) do?

A

Catalyse interconversion of C-OH to C=O

Reduction reaction using NADH

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9
Q

What are the major pituitary hormones regulating steroid hormone synthesis?

A

ACTH
LH
FSH

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10
Q

What hormone has a negative feedback effect on ACTH?

A

Cortisol

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11
Q

What hormones have a negative feedback effection LH and FSH?

A

Testosterone

Oestrogens

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12
Q

What regulates cholesterol import into the mitochondria?

A

LH in gonads

ACTH in adrenal cortex

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13
Q

What imports cholesterol into cells?

A

LDL receptor

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14
Q

What imports cholesterol into mitochondria?

A

Steroidogenic acute regulatory protein (StAR)

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15
Q

What is the acute effect of LH on cholesterol transport?

A

Formation of cAMP and PKA

PKA phosphorylates and activates StAR

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16
Q

What is the chronic effect of LH on cholesterol transport?

A

Gene transcription of steroidogenic enzymes; eg: StAR

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17
Q

What are the two endocrine glands of the adrenal glands?

A

Cortex

Medulla

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18
Q

What are the three regions of the adrenal cortex?

A

Zona glomerulosa
Zona fasciculata
Zona reticularis

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19
Q

What regulates the zona glomerulosa?

A

Renin-angiotension

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20
Q

What does the zona glomerulosa secrete?

A

Minerolcorticoids: aldosterone

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21
Q

What regulates the zona fasciculata?

A

ACTH

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22
Q

What does the zona fasciculata secrete?

A

Glucocorticoids: cortisol

23
Q

What regulates the zona reticularis?

A

ACTH

24
Q

What does the zona reticularis secrete?

A

Androgens

25
Q

What regulates the adrenal medulla?

A

Sympathetic nervous system

26
Q

What does the adrenal medulla secrete?

A

Adrenaline

Noradrenaline

27
Q

How much testosterone is produced by the zona reticularis?

A

Limited because of low enzyme expression under physiological conditions

28
Q

What does a deficiency in aldosterone synthase cause?

A

No aldosterone

Aberrant formation of other hormones

29
Q

What is the two cell model of follicular biosynthesis of oestrogen in the ovaries?

A

Theca cells stimulated by LH
Make progesterone and androstenedione from cholesterol
Thecal cells secrete androstenedione
Granulosa cells take up androstenedione
FSH stimulates increased expression of aromatase in granulosa cells only
Androstenedione converted to estradiol

30
Q

Which enzyme is responsible for converting androstenedione into testosterone in the testes?

A

17 beta-hydroxysteroid hormone dehydrogenase 3 (17beta-HSD 3)

31
Q

In which cells in the testes is testosterone produced?

A

Leydig cells

32
Q

What regulates production of testosterone in the Leydig cells?

A

LH

33
Q

What enzyme activates testosterone in some target tissues?

A

5alpha-reductase

34
Q

What is the more active form of testosterone?

A

Dihydrotestosterone (DHT)

35
Q

How is DHT more active than testosterone?

A

Higher affinity for androgen receptor than testosterone

Longer half life

36
Q

What does a 5alpha-reductase deficiency cause?

A

Failed/incomplete masculinisation of male external genitalia > ambiguous genitalia

37
Q

What proteins transport steroid hormones in the blood?

A

Sex-hormone binding globulin (SHBG)
Cortisol binding globulin (CBG)
Albumin

38
Q

What regulates the expression level of SHBG?

A

Insulin

Thyroid hormones

39
Q

Are the steroid hormones bound to plasma proteins active or inactive?

A

Inactive

40
Q

What are the physiological effects of glucocorticoids?

A 
Decreased
- Glycogen synthesis (in muscles)
- Glucose uptake
- Glucose oxidation
Increased
- Beta-cell dysfunction
- Apoptosis in pancreas
- Insulin secretion
- Gluconeogenesis
- Glycogen synthesis (in liver)
41
Q

How is the inactive steroid hormone receptor stabilised in the cytosol?

A

Bound to chaperone complex

42
Q

How do steroid hormones stimulate gene transcription?

A
  1. Hormone binds to receptor > chaperone complex dissociates
  2. Homodimerisation of steroid hormone receptors > activation
  3. Hormone bound receptor dimer enters nucleus > binds to steroid hormone response elements of target genes > recruitment of co-activator complex
43
Q

What is the response element arrangement of steroid hormone regulated genes?

A

Reverse

44
Q

What do the co-activators recruited by the steroid hormone-recepter homodimer do?

A

Acetylate histones > relaxed nucleosome

45
Q

What causes adrenal hyperplasia in salt-wasting congenital adrenal hyperplasia (CAH)?

A

Insufficient level of corticosterone to cause negative feedback inhibition of synthesis and secretion of ACTH from pituitary
Overstimulation of ACTH receptor in adrenal cortex > hyperplasia

46
Q

What causes virilisation of external genitalia in salt-wasting CAH?

A

Increased flux of intermediates because of overstimulation by ACTH > accumulation of androstenedione > more testosterone in target tissues > virilisation

47
Q

Why is CAH caused by a deficiency of 21alpha-hydroxylase called salt-wasting CAH?

A

Lack of aldosterone > reduced salt re-uptake in kidney

48
Q

What hormones aren’t produced in salt-wasting CAH?

A

Aldosterone

Cortisol

49
Q

What hormones aren’t produced in salt-sparing CAH?

A

Cortisol

50
Q

Which enzyme is deficient in salt-wasting CAH?

A

21alpha-hydroxylase

51
Q

Which enzyme is deficient in salt-sparing CAH?

A

11beta-hydroxylase

52
Q

Why is CAH caused by a deficiency of 11beta-hydroxylase called salt-sparing CAH?

A

ACTH overstimulation > increased aldosterone level

53
Q

What causes the profound hyperandrogenism in patients with aromatase deficiency/mutation?

A

No oestrogen made by granulosa cells

Accumulation of androstenedione > converted to testosterone in other tissues like adrenal cortex

54
Q

Why do patients with aromatase deficiency/mutation show features of accelerated linear growth?

A

Testosterone converted to DHT in bone cells

MD1 Endocrine (18 decks)

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