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4) Metabolic Endocrinology COPY > 6) Anterior Pituitary > Flashcards

6) Anterior Pituitary Flashcards

1
Q

How is the structure of anterior pituitary hormones similar?

A

They are all peptide hormones of varying lengths

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2
Q

Which anterior pituitary hormones have cAMP as the dominant second messenger system?

A
  • ACTH
  • LH
  • FSH
  • TSH
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3
Q

Which anterior pituitary hormones have STAT as the dominant second messenger system?

A
  • GH

- Prolactin

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4
Q

What creates the shorter form of GH? How does it differ from the major form?

A
  • Arises from proteolytic cleavage

- Possesses different biological activities (variants in tissue responsiveness)

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5
Q

How does the degree of glycosylation affect GH variants?

A

Affects their bioactivity, the strength of their signal, and the biological half-life

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6
Q

Human GH was used as a treatment for which illness? What problem occurred?

A
  • Human GH acquired from cadavers was used to treat pituitary dwarfism
  • Problems with prion contamination (Jacob Kreutzfeld disease)
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7
Q

What stimuli causes the release of GH?

A
  • Deep sleep, exercise, stress
  • Decrease in glucose
  • Increase in amino acids
  • Decrease in fatty acids
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8
Q

What hormone inhibits the release of GH from the anterior pituitary? What hormone stimulates the release of GH from the anterior pituitary?

A
  • GHIH (somatostatin) inhibits

- GHRH stimulates

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9
Q

What are the metabolic actions of GH that are unrelated to growth?

A
  • Increase in fat breakdown

- Decrease in glucose uptake by muscles

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10
Q

What mediates the growth-promoting actions of GH? What are they produced by?

A
  • Somatomedins (IGFs)

- Produced by the liver

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11
Q

What are the growth-promoting actions of GH?

A
  • Increase in cellular division
  • Increase in protein synthesis (decrease in blood amino acids)
  • Increase in bone growth
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12
Q

What are the direct actions of GH? (2)

A
  • Mobilization of energy (anti-insulin like effects)

- Promotion of cell differentiation

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13
Q

What is the indirect action of GH?

A
  • Induction of IGF-1 that promotes cell division and has insulin-like effects
  • Promotes growth and endocrine effects
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14
Q

What are the direct anti-insulin like effects of GH?

A
  • Reduced glucose transport and metabolism
  • Increased lipolysis
  • Increased amino acid transport
  • Increased protein synthesis
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15
Q

Is IGF-1 GH-dependent or independent? What about IGF-2?

A
  • IGF-1: GH-dependent

- IGF-2: GH-independent

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16
Q

How are the effects of IGF-1 release mediated?

A
  • IGF-1 released from the liver acts in an endocrine fashion

- In other tissues, local production of IGF-1 allows it to act in a paracrine or autocrine fashion

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17
Q

What is the important function of IGF-2?

A
  • Important role in fetal development

- Role in adults is less clear

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18
Q

How are IGF-binding proteins secreted?

A

Secreted by target cells together with specific proteases

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19
Q

What is the major function of IGF-binding proteins?

A
  • Binding to a carrier protein prevents its degradation to remain at a relatively constant concentration
  • May regulate bioavailability and turnover of IGFs
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20
Q

How do fluctuations of GH affect IGFs?

A

IGFs remain relatively constant over long periods of time, despite fluctuations in GH

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21
Q

During which life stages are the growth-promoting effects of GH via IGF-1 particularly important?

A
  • During childhood growth

- Less important during gestation and for the neonate

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22
Q

What are the growth-promoting effects of GH via IGF-1 influenced by?

A

The nutritional status of an individual

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23
Q

How does aging affect GH pulses?

A
  • Increase with age, with marked rise at puberty

- Then, decline with age

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24
Q

IGF-1 levels parallel _____________ in children.

A

growth rate

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25
Q

On the large-scale, how does GH and IGF-1 affect bone growth? When does that cease?

A
  • Promote bone growth of long bones at the epiphyseal plates (proliferation of chondrocytes)
  • Epiphyses fuse at the end of puberty and longitudinal growth ceases
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26
Q

Specifically, how does GH and IGF-1 affect bone growth?

A
  • GH stimulates fibroblasts to differentiate into chondrocytes
  • IGF increases the number of chondrocytes by stimulating mitosis, which increases the length of the bone
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27
Q

How does IGF-1 produced by the liver affect GH secretion?

A

Negatively feedbacks to the hypothalamus, decreasing GH secretion

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28
Q

Which tissues contain the GH-receptor? When are GH-receptors detectable?

A
  • Most tissues

- 7 months of fetal age

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29
Q

How do GH-receptors act?

A

Via recruitment of tyrosine kinase and activation of STATs, MAPK, and PI-3K

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30
Q

What downregulates the GH-receptor?

A
  • GH

- Other factors, such as sex hormones

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31
Q

What does the IGF-1 receptor ressemble?

A
  • Insulin receptor

- Formed of a dimer of two glycoprotein subunits

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32
Q

How do IGF-1 receptors act?

A

Via intrinsic tyrosine kinase activity

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33
Q

What is the structure of IGF-2 receptors?

A

Single-chain spanning the membrane once

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34
Q

What does the IGF-2 receptor also bind?

A

Mannose-6-phosphate

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35
Q

How do IGF-2 receptors act?

A
  • They have NO signal activity

- But, they’re ultimate function may be via the IGF-1 receptor

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36
Q

What feedback control regulates GH release?

A
  • IGF-1

- GH

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37
Q

How does stress influence GH release? What factors does stress include?

A
  • Stress, including exercise, cold, anesthesia, surgery, hemorrhage
  • Surge in GH
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38
Q

What metabolites increase GH release?

A
  • Hypoglycemia (insulin administration)

- Amino acids (arginine)

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39
Q

What metabolites decrease GH release?

A
  • Hyperglycemia (oral glucose)

- Free fatty acids

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40
Q

Glucose and fatty acids increase ________ release.

A

somatostatin

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41
Q

How does sleep influence GH secretion?

A
  • Sleep induces fluctutations in GH

- Secretion every 1 to 2 hours in a pulsatile fashion

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42
Q

How does GH release vary between sexes? How does GH release vary with age?

A
  • GH is higher in females

- With age, the amount of GH produced and the pulsatility of release decreases in amplitude and frequency

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43
Q

How do you test for the normal regulation of GH secretion?

A
  • Inject glucose into individuals

- Glucose should suppress levels of GH, until the excessive glucose has cleared from the blood

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44
Q

How would glucose infusion affect GH secretion in acromegaly patients?

A
  • Glucose infusion would not affect GH secretion, although it should
  • These patients have lost their ability to regulate GH
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45
Q

How would you test for a deficiency of GH?

A
  • Inject insulin into individuals

- Insulin should cause a hypoglycemic state, which would cause a quick release of GH

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46
Q

How do glucocorticoids affect GH release?

A

Decrease in GH release

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47
Q

How does estrogen affect GH release? Why?

A
  • Increase in GH release

- Sensitizes somatotrophs to produce GH

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48
Q

How does thyroxin affect GH release? Why? What does that explain?

A
  • Increase in GH release
  • Thyroxin promotes transcription of the GH gene
  • Hypothyroid children have stunted growth
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49
Q

When do higher levels of GH occur? When do lower levels occur?

A
  • Higher levels are associated with puberty (peak)

- Decreases with adulthood (somatopause)

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50
Q

What causes GH to peak at puberty?

A

Stimulation of GH release by androgens and estrogens

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51
Q

How do IGF-1 levels vary with age?

A
  • IGF-1 decreases as GH decreases with age

- The maximum levels of IGF-1 are associated with puberty

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52
Q

What benefits does exogenous GH treatment for elderly offer?

A
  • Decreases body fat
  • Increases lean muscle tissue and bone density
  • Improves some cognitive functions
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53
Q

What side effects does exogenous GH treatment for elderly cause?

A
  • Edema in extremities
  • Joint pain
  • Gynecomastia
  • Metabolic imbalances
  • Increased cancer risks
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54
Q

Is GH currently being used as a treatment for the elderly?

A
  • No, since the risks of providing GH have to be carefully assessed
  • But, GH may be purchased illegally
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55
Q

Is prolactin concentration in the pituitary lower or higher than GH?

A

10 times lower than GH

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56
Q

What is the major function of prolactin?

A

Post-partum activation of lactation

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57
Q

What hormones are involved in the growth of the duct system of the mammary gland?

A
  • Estrogen
  • GH
  • Cortisol (adrenal steroids)
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58
Q

What hormones stimulate alveolar growth of the mammary gland?

A
  • Estrogen
  • Progesterone
  • Cortisol
  • Prolactin
59
Q

The secretion of which hormones are essential for the initiation and maintenance of milk secretion?

A
  • Prolactin

- Cortisol

60
Q

How does a hypophysectomy affect milk production?

A
  • Removal of the anterior pituitary gland

- Leads to the immediate cessation of milk production

61
Q

How does an adrenalectomy affect milk production?

A
  • Removal of the adrenal gland

- Gradual reduction in milk production

62
Q

The reduction in which hormones after parturition is permissive for milk production?

A
  • Estrogen

- Progesterone

63
Q

How do prolactin and oxytocin collaborate to stimulate milk let-down?

A
  • Prolactin stimulates milk secretion from alveolar epithelial cells (milk secretion)
  • Oxytocin acts on myoepithelial cells to induce contraction of the alveoli (milk ejection)
64
Q

Which neurotransmitter affects the release of prolactin? How?

A
  • Dopamine

- Decreases release of prolactin

65
Q

What are hyperprolactinemic conditions associated with?

A
  • Hypogonadism (e.g. infertility)
  • High levels of prolactin are associated breastfeeding are associated with lactational amenorrhea (brith control method)
66
Q

How is lactational amenorrhea used as a birth control method?

A
  • Prolactin at high concentrations suppresses the reproductive axis, inhibiting LH and FSH
  • The baby must be fed by the breast consistently to maintain these effects
67
Q

How is prolactin involved in immunomodulation?

A
  • Prolactin receptors are found on B-cells, T-cells, and macrophages
  • Prolactin acts as a mitogen and promotes survival (decreasing apoptosis)
68
Q

Which tissues contain prolactin receptors?

A

Prolactin receptors are found in most tissues, where they act synergistically with many other hormones

69
Q

The mechanism of action of prolactin is similar to which hormone?

A

GH

70
Q

How is the regulation of the effects of prolactin unique?

A
  • Prolactin is mainly under INHIBITORY* control

- In the absence of an inhibitor (dopamine), prolactin secretion increases

71
Q

When do prolactin levels increase during the day?

A

During sleep

72
Q

Which releasing hormones from the hypothalamus stimulate the release of prolactin?

A
  • TRH

- VIP

73
Q

How is ACTH derived?

A

Proteolytic cleavage of a large precursor molecule (POMC)

74
Q

Which hormone may be derived from ACTH? What is its function?

A
  • Melanocyte-stimulating hormone

- Darkening of the skin

75
Q

What hormone may be derived, apart from ACTH, from POMC? What is its function?

A
  • Beta-endorphin

- Morphine-like activity

76
Q

Is the tanning response an endocrine or paracrine response?

A

Paracrine response

77
Q

What skin cells does UV light reach? Are they nucleated or enucleated?

A
  • UV light passes through the enucleated surface skin cells

- They reach paragnocytes, which are nucleated

78
Q

What are the effects of UV light on nucleated skin cells? What are the two possible responses?

A
  • UV light damages DNA
  • Synthesis of p53 protein
  • Or, if the damage of the cell is too great, apoptosis occurs, which results in the loss of skin
79
Q

What is the function of p53 in skin cells that may be repaired?

A
  • p53 stimulates the translation of POMC, which produces MSH
  • MSH binds to a receptor on a melanocyte, activating a signal transduction pathway to produce melanosomes (coloured granules)
80
Q

What is the function of melanosomes in the protection of the skin?

A

Melanosomes are translocated from the melanocyte to the paragnocyte, forming a barrier to deflect UV light

81
Q

What intracellular mechanism occurs following the binding of ACTH to its cognate receptor in the adrenal gland?

A
  • Activates G(alpha)s-protein

- Increase in cAMP

82
Q

What are the effects of ACTH on cholesterol?

A
  • Enhanced mobilization of cholesterol

- Increased conversion of cholesterol to pregnenolone

83
Q

What induces CRH secretion?

A

Stress (pain, fear, fever, hypoglycemia)

84
Q

What are the effects of light/dark cycles on CRH secretion?

A
  • Lowest secretion at midnight

- Increases until a morning peak, and then declines

85
Q

CRH action is potentiated by other hormones, such as what?

A

Vasopressin

86
Q

What is the structural composition of TSH?

A
  • Two glycosylated protein chains

- Alpha and beta subunit

87
Q

What does the beta subunit of TSH provide?

A

Hormone specificity

88
Q

The alpha subunit of which hormones are the same? What differentiates them?

A
  • LH, FSH, TSH

- The beta subunit is different

89
Q

What intracellular mechanism occurs following the binding of TSH to its cognate receptor in the thyroid gland?

A
  • Receptor signalling via G(alpha)s

- Increase in cAMP

90
Q

What is the overall function of TSH?

A
  • Stimulates metabolism of thyroid follicular cells

- Major factor controlling the formation of thyroid hormones

91
Q

What are the three functions of LH in females?

A

1) Steroidogenesis in the ovarian follicle
2) Induction of ovulation
3) Maintenance of steroidogenesis by the corpus luteum

92
Q

What is the function of LH in males?

A

Stimulation of testosterone production in the Leydig cells of the testes

93
Q

What is the function of FSH in females?

A

Stimulation of the development of ovarian follicles and their estradiol secretion

94
Q

What is the function of FSH in males?

A

Spermatogenesis

95
Q

What is a function of FSH that is present in males and females?

A

Secretion of inhibin, which has a negative feedback on FSH

96
Q

What is the major function of inhibin?

A
  • Negative feedback on FSH

- Controls how much LH and FSH are produced relative to each other

97
Q

Describe the release of LH and FSH.

A
  • Pulsatile, occurring every 60 minutes

- In response to GnRH pulses

98
Q

What is the major common cause of disorders of the anterior pituitary?

A

Benign tumours of the pituitary (adenomas)

99
Q

What is the characteristic growth of an adenoma?

A

They are typically slow-growing

100
Q

Differentiate microadenomas and macroadenomas.

A
  • Microadenomas: <10 mm

- Macroadenomas: >10 mm

101
Q

Benign tumours of the pituitary gland arise from which types of cells?

A

Adenohypophyseal

102
Q

Which population group do functional tumours typically affect? What about non-functional tumours?

A
  • Functional tumours: younger

- Non-functional tumours: older

103
Q

Differentiate functional and non-functional tumours.

A
  • Functional tumours cause over-secretion

- Non-functional tumours inhibit secretion

104
Q

Which adenoma type has the largest prevalence?

A

Prolactin cell adenoma

105
Q

Why does prolactin cell adenoma have the highest prevalence?

A
  • Because it is under INHIBITORY control
  • If the connection between the hypothalamus and pituitary is disconnected, the cells react autonomously because the inhibitory control is removed
  • Prolactin is also a mitogen, so if the control is dysregulated, the number of cells will expand
106
Q

What are signs and symptoms of pituitary adenomas usually due to?

A
  • Hypofunction
  • Hyperfunction
  • Mass effect, associated with the location of the adenoma
107
Q

Which structure may be damaged by a pituitary adenoma? What does that result in?

A
  • Impingement on the optic chiasm, causing visual field defects
  • Double vision, drooping eyelids, altered facial sensation
108
Q

What is the most common cause of hypopituitarism? What are other causes?

A
  • Most commonly caused by pituitary adenomas

- Other causes include surgery, radiation, and trauma

109
Q

What is the sequence of function loss from mass effect of hypopituitarism? (4)

A

1) GH
2) LH and FSH
3) ACTH
4) TSH

110
Q

Why is there no function loss for prolactin from mass effect of hypopituitarism?

A

Because hypofunctioning of prolactin is a rare event, as it is controlled by inhibiting factors

111
Q

What are the effects of GH deficiency?

A
  • Decreased muscle strength and exercise tolerance
  • Diminished libido
  • Increased body fat
112
Q

What are the effects of gonadotrophin deficiency?

A
  • Oligo/amenorrhea
  • Diminished libido
  • Infertility
  • Hot flashes
  • Impotence
113
Q

What are the effects of ACTH deficiency?

A
  • Malaise
  • Fatigue
  • Anorexia
  • Hypoglycemia
114
Q

What are the effects of TSH deficiency?

A
  • Malaise
  • Leg cramps
  • Fatigue
  • Dry skin
  • Cold tolerance
115
Q

What is the most common cause of hyperpituitarism?

A

Benign tumours of the pituitary gland

116
Q

How may tumours in the pituitary gland arise?

A
  • De novo

- Or, because of the lack of feedback control (e.g. Cushing disease)

117
Q

Tumours secreting which pituitary hormones are common?

A
  • Prolactin
  • GH
  • ACTH
118
Q

Tumours secreting which pituitary hormones are rare?

A
  • TSH
  • LH
  • FSH
119
Q

What is the most common cure for pituitary adenomas?

A
  • Surgery through the nose

- Remove excess tissue, while still maintaining enough tissue for function

120
Q

What are effects of prolactin excess?

A
  • Oligo/amenorrhea
  • Galactorrhea
  • Infertility
  • Decreased libido
  • Headaches
  • Visual field defects
121
Q

Decreased libido, headaches, and visual field defects are symptoms associated with prolactin excess in which population groups?

A

Men and post-menopausal women

122
Q

What are effects of GH excess?

A
  • Gigantism (young)

- Acromegaly (adults)

123
Q

Why do younger individuals develop gigantism, and not acromegaly?

A

Younger individuals have not finished their growth spurt, which means that their epiphyseal plates are not closed, allowing for the growth of their long bones

124
Q

Describe the release of GH in the presence of a functional pituitary tumour.

A
  • GH produced at a high level without pulsatility

- IGFs are elevated as a consequence

125
Q

How is GH excess due to a functional pituitary tumour treated?

A
  • Long-acting somatostatin analogues

- The best treatment is surgical removal

126
Q

What are the effects of GH therapy in children that have hypofunctioning pituitary glands?

A

Administration of GH allows growth to catch-up

127
Q

What hormone does Cushing’s disease affect?

A

Excess ACTH, leading to excess production of cortisol

128
Q

What are symptoms of Cushing’s disease?

A
  • Buffalo hump
  • Moon face
  • Acne
  • Decrease in immune function (cortisol suppresses the immune system)
129
Q

What are effects of excess TSH?

A
  • Heat intolerance
  • Weight loss
  • Weakness
  • Heart failure
130
Q

What delays the diagnosis of pituitary tumours?

A

The non-specific nature of many symptoms

131
Q

Which technique is used to diagnose pituitary tumours? What may it reveal?

A
  • MRI

- Tests can reveal whether the adenoma is hypo- or hyperfunctional

132
Q

How is a deficiency of GH diagnosed?

A
  • Insulin tolerance test
  • GH-RH/arginine test
  • IGF-1 levels
133
Q

How is a deficiency of gonadotrophins diagnosed?

A
  • Sexual history
  • Menstrual history
  • FSH/LH/estradiol/prolactin/testosterone levels
134
Q

How is a deficiency of ACTH diagnosed?

A
  • Cortisol levels in the AM

- Insulin tolerance test

135
Q

How does ACTH respond to hypoglycaemia?

A

ACTH increases

136
Q

How is a deficiency of TSH diagnosed?

A

T4 and TSH levels

137
Q

How is an excess of prolactin diagnosed?

A
  • Prolactin level
  • Drug history
  • Clinical setting (e.g. pregnancy, breast stimulation, stress, hypoglycemia)
138
Q

What does prolactin level over 200 ng/mL along with a large adenoma suggest?

A

Stalk compression

139
Q

How is acromegaly diagnosed?

A
  • IGF-1 levels

- Oral glucose tolerance test

140
Q

How is Cushing’s disease diagnosed?

A
  • 24-hour urine cortisol

- Overnight dexamethasone suppression test

141
Q

How is an excess of TSH diagnosed?

A

Free T4, T3, and TSH levels

142
Q

What is the first line of treatment for prolactinoma?

A

Dopamine agonist therapy, which suppresses the secretion of prolactin

143
Q

What is the mechanism of action of dopamine agonist therapy?

A
  • Treatment with bromocriptine

- Binds and activates dopamine receptors, inhibiting prolactin secretion

144
Q

What is being used as a treatment for TSH-producing adenomas and acromegaly?

A

Somatostatin analogs

4) Metabolic Endocrinology COPY (15 decks)

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