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Biol 432 > Growth hormone, growth factors, & growth-related diseases > Flashcards

Growth hormone, growth factors, & growth-related diseases Flashcards

1
Q

Growth hormone

A

Growth hormone: a specific polypeptide hormone released into circulation by ant. pit.
somatotroph cells, acts on target cells in the periphery (e.g., in adipose, muscle, bone, liver)

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2
Q

Growth factors

A

a broad/general term often used to mean secreted factors that stimulate
growth (cell proliferation and/or differentiation)

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3
Q

Cytokines

A

a broad/general term for small proteins with cell signaling functions. They have a
fundamental role in the immune system; are typically short-lived and act locally; and a specific
cytokine may often be produced by multiple cell types

Broad range of functions (which may include promoting growth), but historically
categorized as cytokines when exerting immunological or hematopoietic responses

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4
Q

Hormones, growth factors, and cytokines: …

A

all chemical messengers/signaling molecules that bind to specific receptors, initiating signal transduction pathways and biological responses

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5
Q

Growth factors and cytokines have some similarities in structure to ___ hormones; they also act on cell ___ receptors (and receptors have structural homologies);
might share ____ signaling components

A

• Growth factors and cytokines have some similarities in structure to peptide hormones;
they also act on cell surface receptors (and receptors have structural homologies);
might share downstream intracellular signaling components

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6
Q

Growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis

GH

A 
191-a.a. polypep@de hormone
synthesized by anterior pituitary
somatotroph cells;
~ half in circulaNon is bound to
specific GH-binding proteins (GHBP)
(reduce oscillaNons, prolong half-life)
• High-affinity GHBP is the same as the
extracellular porNon of GH receptor
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7
Q

Growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis

IGF-1

A

70-a.a. polypep@de hormone
synthesized by many Nssues
(paracrine/autocrine signaling), and most
IGF-1 in circula@on (endocrine signaling) is
produced by liver; bioavailability is
determined by specific IGF binding proteins

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8
Q

Growth hormone (GH) signaling

• GH:

A

• GH: linked to nutritional status; promotes

↑ lean mass & using lipid/carbohydrate stores

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9
Q

Most growth-promoting effects of GH are

mediated by IGF-1 (“indirect” effect of GH)

A
  • GH stimulates liver to produce IGF-1 (into
    circulation), and stimulates local (autocrine
    /paracrine) IGF-1 production by most tissues
  • Well-known effects in bone & skeletal muscle
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10
Q

GH also has ____

A

GH also has metabolic effects

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11
Q 
Growth hormone (GH) signaling
Liver
A

Liver: stimulates glucose release (energy
source), in addition to release of IGF-1
• White adipose tissue: stimulates lipolysis and
release of fatty acids (energy source), while
inhibiting uptake of lipids from circulation
• w/IGF-1, promotes protein accumulation
(increases a.a. uptake & protein synthesis)

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12
Q

GH: linked to nutritional status . fasting _____, potentially to mobilize lipids as an energy source & prevent protein loss

A

• GH: linked to nutritional status – fasting
stimulates GH secretion, potentially to mobilize
lipids as an energy source & prevent protein lo

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13
Q

ghrelin

A

• e.g., via ghrelin, the “hunger hormone”
produced by enteroendocrine cells of GI tract,
which binds to receptors on somatotroph
cells and potently stimulates GH secretion

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14
Q
  • Rise in glucose or free fatty acids = ___ GH
  • Protein-high meal or a.a. infusion = __ GH release
  • Stress, exercise, and sleep all lead to ___ GH
A
  • Rise in glucose or free fatty acids = ↓ GH
  • Protein-high meal or a.a. infusion = ↑ GH release
  • Stress, exercise, and sleep all lead to ↑ GH
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15
Q

Age affects GH levels (___ levels in children,

drops in adulthood)

A

Age affects GH levels (high levels in children,

drops in adulthood)

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16
Q

Growth hormone (GH) signaling – GH receptor is a Type 1 cytokine receptor

step 1

A
  1. Different portions of a single GH associate with two independent GHR, leading to JAK2 recruitment
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17
Q

Growth hormone (GH) signaling – GH receptor is a Type 1 cytokine receptor

step 2

A 
2. JAK2 undergoes
autophosphorylation &
phosphorylates the GHR,
providing a docking site
for a STAT (signal
transducers and activators
of transcription).
18
Q

Growth hormone (GH) signaling – GH receptor is a Type 1 cytokine receptor

step 3

A 
3. STAT is then
phosphorylated by JAK2,
and can form dimers that
translocate to the nucleus
and regulate transcription
of its target genes (e.g.,
stimulates IGF-1 gene
expression).
19
Q

Thyroid hormone:

A

promotes GH secretion and GH’s growth & metabolic effects;

Hypothyroidism in children leads to reduced growth after birth & developmental delays

20
Q

Gonadal sex steroids

A

• Gonadal sex steroids: important for puberty growth spurt

Estradiol stimulates IGF-1 production and also promotes GH secretion

21
Q 
Glucocorticoids : high levels can
\_\_\_ growth (due to \_\_\_
endogenous levels/hypersecretion,
A 
\: high levels can
suppress growth (due to excess
endogenous levels/hypersecretion,
22
Q

Synergistic actions of hormones
e.g., growth hormone (GH) &
thyroid hormone (TH)

A

Synergistic actions of hormones
e.g., growth hormone (GH) &
thyroid hormone (TH)

23
Q 
e.g., Cushing syndrome,
or due to exogenous glucocorticoids,
e.g. steroid treatments);
Glucocorticoids \_\_\_\_
somatostatin secretion
A 
e.g., Cushing syndrome,
or due to exogenous glucocorticoids,
e.g. steroid treatments);
Glucocorticoids increase
somatostatin secretion
24
Q

Acromegaly

A
  • excess GH (and therefore high IGF-1) after puberty

- Most often because of excessive GH secretion (e.g., GH-secreting pituitary adenomas)

25
Q

Growth hormone axis deficiency

A

Abnormalities at various levels of the axis

26
Q

GH deficiency

A

(GH gene defect, pituitary defect, hypothalamic dysfunction)

– therefore, low levels of IGF-1

27
Q

Laron syndrome

A

: GH resistance, or deficiency in GH receptor (and GH binding protein),
or IGF-1 or IGF-1 receptor defect – any could result from gene mutations

28
Q

GH levels are ___ under GH resistance, but IGF-1 levels are ____;
low IGF-1 levels mean lack of ___ feedback inhibition, and ∴ ___ in circulating GH

A

GH levels are elevated under GH resistance, but IGF-1 levels are low or absent;
low IGF-1 levels mean lack of negative feedback inhibition, and ∴ rise in circulating GH

29
Q

Other factors that affect growth

A

Genetics affect height in adulthood

• Nutritional and socioeconomic factors
Malnutrition is a major player that can cause significant endocrine changes
e.g., elevated GH levels but GH resistance (e.g., ↓ GH receptors) and decreased IGF-1

• Chronic disease
Many chronic systemic diseases interfere with growth

• Psychological factors
Psychological stress or psychiatric disease can affect endocrine function or nutrition

30
Q

Placenta

A

: endocrine organ that is critical for fetal growth
• Supplies nutrients and oxygen
• Produces & releases many hormones and growth factors

31
Q

• Insulin-life growth factors (IGFs)

A

• Insulin-life growth factors (IGFs) are important for fetal growth, but
IGF-1 in the fetus is regulated by metabolic factors other than GH (few GH receptors)

32
Q

IGF-2

A

• IGF-2 is more abundant during fetal life than IGF-1

33
Q

Insulin

A

• Insulin also has important stimulatory effects on fetal growth

34
Q

Growth factors

A

a broad/general term often used to mean secreted factors that stimulate
growth (cell proliferation and/or differentiation)

35
Q

Growth factor receptor

A

: the enzyme tyrosine kinase is part of the receptor…

36
Q

_____ of tyrosine residues in receptor creates docking sites to
recruit adaptor proteins & effectors (forming a ____);
And phosphorylating docked proteins
(e.g., other kinases)
regulates their enzymatic activity,
causing a ________

A

Autophosphorylation of tyrosine residues in receptor creates docking sites to
recruit adaptor proteins & effectors (forming a signaling complex);
And phosphorylating docked proteins
(e.g., other kinases)
regulates their enzymatic activity,
causing a phosphorylation cascade

37
Q

Insulin-like growth factors (IGF-1 & IGF-2):

A

Both are in the same family of peptides as insulin (common ancestral gene)
IGF-1 receptor and insulin receptor are highly homologous,
with many similarities in downstream signaling pathways

38
Q

Too little growth factor might cause ____ (= children’s weight or rate of weight gain
is significantly below that of other children of similar age and sex)

A

Too little growth factor might cause failure to thrive (= children’s weight or rate of weight gain
is significantly below that of other children of similar age and sex)

39
Q

• Proto-oncogenes

A

normal genes that affect cell growth, but can become oncogenes
(genes with the potential to cause cancer) when something goes awry
• e.g., mutation in a growth factor gene, its receptor,
or a component of its signaling cascade

40
Q

Therefore, one disease that is associated with too much growth factor is ___

A

Therefore, one disease that is associated with too much growth factor is cancer
…and tumors can cause increased secretion of growth factors

Biol 432 (8 decks)

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