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Gabe's Endocrinology > Steroid Hormones > Flashcards

Steroid Hormones Flashcards

1
Q

What are human steroids derived from?

A

Dietary steroids or are made from acetyl-CoA in the liver

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2
Q

What is the most abundant steroid?

A

Cholesterol

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3
Q

Where is cholesterol found?

A

Free in membranes and as esters in storage (liver, lipoproteins and atherosclerotic plaque)

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4
Q

What are 2 major corticosteroids?

A
  • Glucocorticoids (cortisol)
  • Mineralocorticoids (aldosterone)
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5
Q

What do glucocorticoids regulate?

A

Metabolism and immune function

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6
Q

What do mineralocorticoids maintain?

A

Blood volume and control renal excretion of electrolytes

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7
Q

What are the 3 classes of sex steroids?

A

Androgens, estrogens, and progestagens

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8
Q

What do sex steroids do?

A

Produce sexual differences and support reproduction.

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9
Q

Where are oestrogen and progesterone made?

A

Primarily in the ovary and in the placenta during pregnancy.

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10
Q

Where is testosterone made?

A

In the testes

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11
Q

What is testosterone converted into? Why?

A

Oestrogen to regulate the supply of each in both females and males.

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12
Q

What is one example of a pharmaceutical application of steroids?

A

The anti-inflammatory drug dexamethasone

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13
Q

How can breast and prostate cancer be treated by steroids?

A
  • By lowering or blocking gender specific steroids.
  • Tamoxifen blocks oestrogen and Leuprolide lowers testosterone.
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14
Q

What do anabolic steroids interact with?

A

Androgen receptors to increase muscle and bone synthesis.

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15
Q

How does the body get cholesterol?

A

It’s made in the liver or absorbed from the diet.

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16
Q

How does the liver export cholesterol?

A

In lipoproteins

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17
Q

What do endocrine tissues do to cholesterol?

A

Modify it to steroid hormones

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18
Q

What is cholesterol synthesised from?

A

Acetyl-CoA

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19
Q

What is inhibited through negative feedback to decrease synthesis of cholesterol?

A

HMG-CoA reductase

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20
Q

What is converted to cholesterol in the endoplasmic reticulum?

A

Squalene

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21
Q

What eliminates steroids after they have been oxidised?

A

Cytochrome P450.

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22
Q

What determines the steroid half-life?

A

The rate at which it is turned over.

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23
Q

What is the most significant pathway for steroid turnover?

A

CYP3A4 in liver endoplasmic reticulum

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24
Q

What is CYP3A4?

A

The most abundant P450 in the human body, constituting 28% of total CYPs in humans.

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25
Q

What is the MoA of CYP3A4?

A

Introduces -OH into the steroid ring then other enzymes form bile acids.

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26
Q

What do steroids change?

A

Gene expression

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27
Q

What is the MoA of steroids?

A
  • They enter the cells and bind to internal receptors.
  • Steroid-receptor complex binds at Hormone Response Elements in DNA.
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28
Q

What is the MoA for sex steroids?

A

Direct pathway: Protein bound steroid hormone dissociates from protein, enters cell and goes into nucleus, binds to nuclear receptor which then binds to hormone response elements in the DNA, inducing gene expression changes.

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29
Q

What is the MoA for mineralocorticoids and glucocorticoids?

A

Indirect pathway: Protein bound steroid hormone dissociates from protein, enters cell and goes into cytosol, binds to non-DNA-binding cytoplasmic receptor. Receptor is then activated by heat-shock protein and translocates to the nucleus and is then activated

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30
Q

What are all steroids stimulators of?

A

Protein synthesis via a direct or indirect link

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31
Q

What does the nuclear androgen receptor do?

A

Allows male sex steroids to mediate the male phenotype.

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32
Q

What is used to treat hirsutism in females?

A
  • Cyproterone acetate is a synthetic steroid inhibitor of androgen receptor.
  • It blocks synthesis of mRNA for androgenic proteins.
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33
Q

What is a common component in hormone therapy for male-to-female gender change?

A

Cyproterone acetate

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34
Q

What does ACTH stimulate?

A

Release of corticosteroids from the adrenal cortex.

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35
Q

What do corticosteroids stimulate?

A
  • Na+ uptake
  • Stress adaptation
  • Anti-inflammatory and immunosuppressive effects.
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36
Q

What does the adrenal medulla secrete?

A

Catecholamines (adrenaline and noradrenaline)

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37
Q

What are the 3 major steroid hormones of humans secreted from the adrenal cortex?

A
  • DHEA
  • Cortisol
  • Aldosterone.
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38
Q

Where is DHEA secreted from?

A

Reticularis cells of adrenal cortex

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39
Q

Where is cortisol secreted from?

A

Fasciculata cells of adrenal cortex

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40
Q

Where is aldosterone secreted from?

A

Glomerulosa cells of adrenal cortex

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41
Q

What is the secretion signal for DHEA and cortisol?

A

ACTH

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42
Q

What is the secretion signal for aldosterone?

A

Angiotensin II/III and ACTH

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43
Q

What is the function of DHEA?

A
  • Various protective effects of adrenal cortex (anti-cancer; anti-aging)
  • Weak androgen
  • Can be converted to oestrogen.
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44
Q

What is the function of cortisol?

A
  • Stress adaptation of adrenal cortex through various cellular phenotypic expressions
  • Regulates protein, carbohydrate and lipid metabolism
  • Immunosuppressive effects.
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45
Q

What is the function of aldosterone?

A
  • Causes sodium ion reabsorption in kidney via conductance channels
  • Controls salt and water balance
  • Raises blood pressure by increasing fluid volume.
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46
Q

What do mineralocorticoids promote?

A
  • Retention of sodium and water
  • Mineralocorticoids are typically produced at 1/100th the level of glucocorticoids.
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47
Q

What is the primary mineralocorticoid?

A

Aldosterone

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48
Q

What hormones other than aldosterone have mineralocorticoid functions?

A

Progesterone and deoxycorticosterone

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49
Q

What stimulates secretion of aldosterone?

A

Angiotensin II, ACTH and local K+ levels.

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50
Q

What is the MoA of mineralocorticoids?

A

Bind to the cytosolic mineralocorticoid receptor then translocate into the cell nucleus.

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51
Q

What role does the heat shock protein play in the MoA of mineralocorticoids?

A

If the hormone is absent, the receptor binds the heat shock proteins and prevents the transcription of targeted genes.

52
Q

What is the MoA of aldosterone release from the glomerulosa cells of the adrenal cortex?

A
  • Angiotensins, acetylcholine (stress) and ACTH cause influx of Ca2+
  • Activates protein kinase C.
  • PKC phosphorylates and activates the rate limiting enzymes for aldosterone synthesis.
  • Aldosterone is secreted into extracellular space and bloodstream.
53
Q

What is the major glucocorticoid hormone?

A

Cortisol

54
Q

What opposes cortisol?

A

DHEA

55
Q

What is cortisol?

A

A stress hormone that promotes gluconeogenesis (flight-fight response) for brain and muscles to get glucose.

56
Q

What is DHEA?

A

An anabolic androgen.

57
Q

What does cortisol stimulate?

A

Protein breakdown to amino acids (gluconeogenic).

58
Q

What does cortisol inhibit?

A

Protein synthesis and the utilization of glucose by adipose tissue

59
Q

What does cortisol increase?

A

Blood glucose levels

60
Q

What effect does cortisol have on adipose tissue?

A

Facilitates lipid breakdown in major adipose tissue to fatty acids.

61
Q

What do individuals with excess cortisol often experience?

A
  • Abnormal fat deposition.
  • Cortisol promotes fat deposition in the abdomen and head and chest area.
62
Q

How does cortisol stimulate weight gain?

A

By stimulating appetite and excessive eating

63
Q

What is the MoA of cortisol from zona fasciculata?

A
  • ACTH from pituitary binds G-protein receptor
  • Activates PKA
  • Transports cholesterol into mitochondrion and is converted into cortisol, which is then secreted.
64
Q

What effect do glucocorticoids have on immune and inflammatory responses?

A

Suppress cytokines synthesis

65
Q

What is the MoA of immune suppression by glucocorticoid?

A
  • TNF (Tumour Necrosis Factor) initiates destruction of the inhibitor IκBα.
  • Glucocorticoid (GC) elevates the inhibitor and opposes the production of cytokines.
66
Q

What is dexamethasone?

A
  • Potent synthetic glucocorticoid that acts as an anti-inflammatory and immunosuppressant.
  • It is 20 to 30 times more potent than the naturally occurring hormone cortisol and 4 to 5 times more potent than prednisone
67
Q

What is dexamethasone used to treat as an anti-inflammatory?

A
  • Inflammatory and autoimmune conditions, such as rheumatoid arthritis. It is useful to counteract allergic anaphylactic shock, if given in high doses.
  • Often administered before antibiotics in cases of bacterial meningitis.
  • Then acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics
68
Q

Why are cancer patients given dexamethasone?

A
  • To counteract a range of side-effects of their antitumor treatment, including nausea and oedema.
  • Dexamethasone is a direct chemotherapeutic agent in multiple myeloma.
69
Q

How is dexamethasone used in obstetrics?

A

Helps women at risk of delivering prematurely to promote maturation of the foetal lungs.

70
Q

When is dexamethasone used in adrenal insufficiency and Addison’s disease?

A

Dexamethasone is prescribed when the patient does not respond well to prednisone or methylprednisolone.

71
Q

What are the applications of beclomethasone nasal spray (beconase)?

A
  • Treat the nasal symptoms of allergies and other seasonal reactions.
  • Prevents the recurrence of nasal polyps following surgical removal.
72
Q

What is beclomethasone droproprionate?

A

An analogue of dexamethasone.

73
Q

What is the MoA of beclomethasone?

A

It is hydrolyzed via esterase enzymes to its active metabolite beclomethasone-17-monopropionate (B-17-MP), which has high topical anti-inflammatory activity

74
Q

What is prednisolone?

A

An oral steroid used for the treatment of asthma.

75
Q

What does prednisolone do?

A

Breathing becomes easier and wheezing, cough, mucus production, and chest tightness all gradually lessen. Other allergic diseases, such as eczema and nasal congestion or drip, are also likely to be helped by the anti-inflammatory action of the oral steroids. Many people report a powerful boost of energy—for a short time.

76
Q

What are the undesirable side effects of prolonged use of oral steroids?

A
  • Cataracts
  • Osteoporosis
  • Myopathy
  • Fragile skin
  • Hirsutism
77
Q

What are the 2 different treatments for asthma?

A
  1. Ventolin - non-steroidal short-acting beta-2 agonist to relax muscles.
  2. Prednisolone - steroid
78
Q

What is GnRH?

A

Gonadotrophin releasing hormone.

79
Q

What is GnRIF?

A

Gonadotrophin releasing inhibitory factor.

80
Q

What does GnRH stimulate?

A

Release of FSH and LH from the anterior pituitary.

81
Q

What does GnRIF do?

A

Inhibits release of FSH and LH from the anterior pituitary.

82
Q

Where are GnRH and GnRIF released from?

A

Hypothalamus

83
Q

What organs do FSH and LH act on?

A

Testes and ovaries

84
Q

What does LH do?

A

Stimulates release of testosterone from testes or progesterone from ovaries.

85
Q

What does FSH do?

A

Stimulates release of oestradiol from ovaries or spermatogenesis in the testes.

86
Q

What is Leuprorelin?

A

GnRH analogue.

87
Q

What is Leuprorelin used for?

A

To induce chemical castration via inhibition of FSH and LH release.

88
Q

What effect does Leuprorelin have on women?

A

Complete suppression of oestrogen and progesterone from the ovaries.

89
Q

What effect does Leuprorelin have on men?

A

Complete suppression of testosterone from the testes.

90
Q

What can Leuprorelin be used to treat?

A

Breast, ovarian and prostate cancer

91
Q

What is the MoA of Leuprorelin?

A

Interrupts the normal pulsatile stimulation of the GnRH receptors to indirectly downregulate secretion of LH and FSH.

92
Q

What are the 3 major sex steroids?

A

Progesterone, oestradiol and testosterone.

93
Q

Where is progesterone secreted from?

A

Corpus luteum

94
Q

What is the secretion signal for progesterone?

A

LH

95
Q

What is the function of progesterone?

A

Maintains (with eostradiol) the uterine endometrium for implantation of fertilised oocyte; differentiation of mammary glands.

96
Q

Where is oestradiol secreted from?

A

Ovarian follicle and corpus luteum (sertoli cell)

97
Q

What is the secretion signal for oestradiol?

A

FSH

98
Q

What are the functions of oestradiol in females?

A

Regulates gonadotropin secretion in ovarian cycle; maintains (with progesterone) uterine endometrium; growth of mammary gland

99
Q

What are the functions of oestradiol in males?

A

Negative feedback inhibitor of Leydig cell synthesis of testosterone

100
Q

Where is testosterone secreted from?

A

Leydig cells of testes; (adrenal gland); ovary

101
Q

What is the secretion signal for testosterone?

A

LH

102
Q

What are the functions of testosterone in males?

A
  • Required for spermatogenesis
  • Converted to more potent androgen
  • Dihydrotestosterone, in some target tissues like prostate gland
  • Secondary sex characteristics (in some tissues testosterone is active hormone)
103
Q

What do sex steroids bind to?

A

Sex hormone-binding globulin (SHBG)

104
Q

What is the precursor for all sex steroids?

A

Cholesterol

105
Q

What provides negative feedback to the hypothalamus to reduce the stimulation of LH and FSH release?

A

LH and FSH

106
Q

What is the usual pregnancy test?

A

hCG

107
Q

When is hCG at its maximum?

A

At the end of first trimester

108
Q

What controls the production of testosterone by the testes?

A

Pituitary gland

109
Q

What does testosterone stimulate in males?

A

Cells in the testes to produce sperm

110
Q

What inhibits LH in males?

A

FSH

111
Q

Where is more than 95% of testosterone produced in men?

A

By Leydig cells

112
Q

What do sertoli cells require for spermatogenesis?

A

Testosterone

113
Q

Where is testosterone produced in both sexes?

A

Zona reticularis of the adrenal cortex

114
Q

Where do women produce small quantities of testosterone?

A

In ovaries and placenta

115
Q

What does growth of prostate and breast cancers depend on?

A

Sex steroids - cancers still retain some character of their own.

116
Q

What do many prostate cancers depend on?

A

Testosterone

117
Q

What does androgen deprivation therapy do?

A

Reduces the production or blocks the effect of testosterone

118
Q

What do Leuprorelin or Leuprolide do in the treatment of prostate cancer?

A

Agonists of receptors for release of LH and FSH, which reduce testosterone release.

119
Q

What are the common side effects of HRT in men?

A

Poor erections or impotence ,weight gain, reduced libido, reduced muscle strength, altered body hair and skin texture, breast changes, fatigue, changes in appetite, sweating, dry eyes, hot flushes, mood swings, memory problems, balance problems, reduced ability to concentrate, insomnia and reduced bone strength (osteoporosis).

120
Q

What is tamoxifen?

A

An oestrogen receptor antagonist in breast tissue, used to treat breast cancer.

121
Q

What is Letrozole?

A

An aromatase inhibitor used to treat local or metastatic breast cancer.

122
Q

What happens to oestrogen levels in post-menopausal women? What does this mean for breast cancers?

A
  • Drop to extremely low, causing growth arrest and/or apoptosis of hormone-responsive cancer cells
  • An off-label use is for ovarian stimulation for IVF (low oestrogen stimulates FSH release).
123
Q

What effect do anabolic steroids have on muscle?

A
  1. Increase production of actin and myosin.
  2. Reduce exercise recovery time by blocking the effects of the glucocorticoid stress hormone cortisol on muscle tissue so that catabolism of muscle is greatly reduced.
  3. Decrease fat indirectly by increasing basal metabolic rate (BMR), so fat is depleted to provide energy for the elevated muscle mass.
124
Q

What is Dianabol?

A

Anabolic steroid

125
Q

What are the physical side effects of anabolic steroids?

A
  • Liver damage
    High blood pressure
  • Jaundice
  • Renal failure
  • Acne
126
Q

What are the psychiatric effects of anabolic steroids?

A

Delusions, jealousy, paranoia, irritability, and feelings of invincibility.

Gabe's Endocrinology (17 decks)

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