hormones and growth - notes

Question 1

hormones most relevant in growth

Answer 1

GH
thyroid hormones
insulin
androgens
estrogens
glucocortocoids
peptide growth factors

Question 2

why would malnutrition prevent growth?

Answer 2

malnourished tissues are refractory to the actions of many hormones

Question 3

growth hormone

Answer 3

1: promotion of skeletal growth
2: stimulation of soft tissue growth

Question 4

GH on linear growth

Answer 4

affects chondrogenesis

Question 5

GH on soft tissue growth

Answer 5

increases cell number and size

Question 6

HGH and insulin

Answer 6

antagonizes effects of insulin on liver and muscle

directly or indirectly via somatomedins

Question 7

forms of HGH

Answer 7

major forms: one of 22000 D and one of 20000 D
produced by anterior pituitary
also larger form and several smaller forms in pit
big and big-big in plasma

Question 8

somatotrope cells

Answer 8

produce HGH
most numerous in anterior pituitary
predominate in lateral wings where lactotrope cells also found
acidophiles

Question 9

GH on metabolism

Answer 9

1: increased protein synthesis and AA uptake by tissues (promotes positive N2 balance)
2: increased RNA and DNA synthesis
3: increased connective tissue growth and skeletal growth
4: increased acid mucopolysaccharide formation in skin and cartilage
5: hyperglycemia via antiinsulin or diabetogenic action
6: increased retention of Na, K, Cl, Mg, PO4, and Ca
7: increased lipolysis => increased fat mobilization

Question 10

changes in GH effects on metabolism over time

Answer 10

for first few minutes, exhibits insulin-like activities on glucose uptake and on free FA utilization
then changes to anti-insulin effects such as increasing plasma glucose levels and increasing circulating FFA
initial effects due to somatomedins

Question 11

what effect would removal of the pituitary have on adolescents with juvenile diabetes

Answer 11

would reduce insulin requirements

Question 12

how is commercially available HGH produced?

Answer 12

recombinant technology

Question 13

stimulatory factors in HGH release

Answer 13

hypoglycemia

1: hypothalamus is directly responsive to circulating glucose levels - produce GHrH, somatotropin releasing factor, somatocrinin => GH release
2: increased blood levels of AA, esp. arginine - GH levels increase 2-4 hours after a meal
3: deep sleep (stage 3 and 4) - turned off by REM sleep
4: diurnal variation in GH release - peak levels in evening and early morning
5: exercise - likely correlates with FFA utilization for energy
6: GHRH from hypothalamus
7: brain GHRP/gerlin (growth hormone releasing peptide) => increased GHRH, decreased somatostatin

Question 14

what are provocative tests for hGH?

Answer 14

insulin, arginine, L-dopa, conidine

must use at least two and take multiple samples throughout day because levels fluctuate so much

Question 15

inhibitory factors in HGH release

Answer 15

1: REM sleep
2: somatomedins (IGFs) - hGH increases production - mediate effects of hGH on tissues - ones released by liver are mainly responsible for circulating levels - negative feedback
3: primary hypothyroidism via inhibitory effects of excessive TRH on somatotropes
4: high FFA levels

Question 16

growth hormone deficiency

Answer 16

usually associated with deficiencies of other pituitary hormones too
pubertal development delayed
growth stunted => dwarfism
must treat before full bone maturation
usually due to hypothalamic dysfunction or pituitary lesion or failure of tissues to respond to GH (s.a. laron dwarfism and african pigmyism

Question 17

laron dwarfism and african pigmyism

Answer 17

GH deficiency syndromes
HGH levels are high and somatomedin leves are subnormal
either receptor or post-receptor defect leading to the symptoms of GH deficiency (ie tissues aren’t responding properly to GH)
somatomedin C levels low in hypopituitary dwarfs
can use it to treat this sometimes

Question 18

growth hormone hypersecretion

Answer 18

usually due to tumor of pituitary
can cause pituitary gigantism if before epiphyseal plates sealed
if after bone maturation, acromegaly
plasma HGH and somatomedin C levels elevated in both
treat with microhypophysectormy, radiation, or drugs that inhibit HGH secretion (s.a. bromocriptine)

Question 19

acrogmegaly

Answer 19

pituitary tumor after epiphyseal plates have fused
connective tissue proliferation
dermal overgrowth
enlargement of extermities
plasma HGH and somatomedin C levels elevated
treat with microhypophysectormy, radiation, or drugs that inhibit HGH secretion (s.a. bromocriptine)
somatomedin C levels elevated

Question 20

insulin in growth

Answer 20

hyperinsulin before or after birth => excessive growth
deficiency => growth failure
fills permissive role
affects possible due to its structural similarity to somatomedin C (IGF-1)

Question 21

nerve growth factor

Answer 21

may mediate role of thyroid hormones in development of brain during last part of gestation and for several months of postnatal development (for growth of ganglia in fetal life, maintaining sympathetic nervous system postnatally)
118 AA, derived from dimer with 3 subunits
beta subunit is biologically active
produced by number of tissues
differentiating factor
production stimulated by androgens and thyroid hormones

Question 22

thyroid hormones in neural development

Answer 22

required for brain development during last part of gestation and for several months of postnatal development
may be mediated by NGF

Question 23

hypothyroidism and growth

Answer 23

children with this have severely retarded growth
increase protein and RNA synthesis, possibly increase in DNA synthesis
could have permissive role
since HPA mechanisms controlling GH and TH release are interrelated, problems in TH may reduce stores and release of GH
also appear to prime tissues to respond to somatomedins

Question 24

sex hormones in growth

Answer 24

promote protein synthesis and hence N2 retention
androgens responsible for adolescent growth spurt
androgenation associated with muscular growth
but need GH to have effect - act synergistically to enhance linear growth
promote bone maturation that ultimately leads to closure of plates

Question 25

estrogen on growth

Answer 25

may have some inhibitory effect, possible mediated by reduction of somatomedin release in response to GH

Question 26

glucocorticoids in growth

Answer 26

hormones of adrenal cortex when in high amounts, catabolic effect on peripheral growth but cortisol has anabolic effects on liver and is required as permissive agent in some processes interferes with action of somatomedin C on cartilage normally negative effects on protein synthesis can become synthesis-enhancing when the hormones given together with certain tissue growth factors

Question 27

cortisol in growth

Answer 27

has anabolic effects on liver and is required as permissive agent in some processes interferes with action of somatomedin C on cartilage

Question 28

adrenal virilizing hyperplasia

Answer 28

one condition in which glucocorticoids can be used to promote growth, despite the fact that glucocorticoids are generally catabolic

Question 29

somatomedins

Answer 29

peptide growth factor mediate growth-promoting actions of GH 5: A, B, C, IGF-1, IGF-2

Question 30

somatomedin B

Answer 30

not regulated by GH | promotes thymidine incorporation in culture, but is essentially an antiprotease

Question 31

somatomedin A

Answer 31

release regulated by GH neutral peptide with no disulphide bonds promotes growth of cartilage and thymidine incorporation by cells

Question 32

somatomedin C and IGF-1

Answer 32

now thought identical structurally related to proinsulin 70 aa, can be divided into 3 domains (A, B, C) A and B about 50% identical with proinsulin structure remains intact (A, B, and C not divided) serum levels provide some index of GH activity on tissue targets - leves rise with age in prepubertal children, peak during puberty, and fall in adulthood levels low in hypopituitary dwarfs, elevated in acromegaly

Question 33

IGF-1 and IGF-2

Answer 33

whats though of as somatomedins structurally related to proinsulin released from liver by GH likely mainly responsible for circulating levels of peptides tissues levels increase dramatically in response to hGH (more so than plasma levels) - may chiefly be paracrine

Question 34

IGFBPs

Answer 34

bind somatomedins in plasma - 85% bound | produced by liver and GH target tissues

Question 35

plasma levels of IGF-1 and IGF-2

Answer 35

in normal adults: IGF-1 levels average about 200 ng/mL IGF-2 levels average about 650 ng/mL

Question 36

IGF-2 receptor (type 1)

Answer 36

on cell membranes alpha and beta subunits linked by disulfide bonds insulin can also bind, but with low affinity (IGF-1 also has weak affinity for insulin receptors)

Question 37

actions of IGF-1 in cells

Answer 37

1: stimulates DNA synthesis and cell division 2: promotes sulphate incorporation into proteoglylcans of cartilage and connective tissue 3: differntiation of myoblasts into myotubules in muscle 4: myoblast proliferation 5: can also have insulin-like actions 6: in adipose tissue can stimulate glucose oxidation and the synthesis of lipids

Question 38

IGF-2 receptor

Answer 38

type 2 receptor | insulin has no binding affinity

Question 39

actions of IGF-2 in cells

Answer 39

1: IGF-2 has higher binding affinity for insulin receptor than does IGF-1 so has more potent insulin-like actions on muscle and adiopse 2: promotes cell division 3: promotes RNA synthesis 4: promotes protein synthesis

Question 40

platelet derived growth factor (PDGF)

Answer 40

basic peptide 2 chains (a, B) united by disulphide bridge may be involved in development of atherosclerosis

Question 41

actions of PDGF on growth

Answer 41

1: promotes growth of fibroblasts and SMCs by acting as a competence factor - once cells competent, they can undergo mitosis in response to appropriate stimuli (s.a. that from IGF-1 or EGF)

Question 42

PDGF receptor

Answer 42

membrane protein | activation leads to increased tyrosine kinase activity and increased conversion of membrane phospholipid to IP3 and DAG

Question 43

fibroblast growth factor (FGF)

Answer 43

peptide isolated from pituitary and brain seems to stimulate cell proliferation by acting as a competence factor

Question 44

epidermal growth factor (EGF) structure

Answer 44

53 aa, 3 disulphide bridges derived from 1200 AA precursor (2 molecules of EGF and 2 molecules of a binding subunit) binding subunit cleaves precursor to form an active peptide that has paracrine or autocrine role produced by many different tissues throughout body

Question 45

EGF actions

Answer 45

paracrine or autocrine role | stimulates cell proliferation in epithelial cells and in cells of mesodermal origin

Question 46

EGF receptor

Answer 46

membrane glycoprotein with extracellular and intracellular components intracellular is tyrosine kinase - autophosphorylates when EGF binds, entire hormone-receptor complex becomes internalized

Question 47

erythropoietin

Answer 47

produced by kidneys stimulates proliferation of primitive hematopoietic stem cells promotes conversion of proerythrocytes to erythrocytes regulated by states of tissue oxygenation, stimulated by hypoxia

Question 48

interleukins

Answer 48

peptide products of lymphocytes

Question 49

IL-1

Answer 49

``` single-chain product of monocyte macrophages stimulates: 1: thymocyte mitosis 2: growth of activated T-lymph 3: T-lymph reactivity ```

Question 50

IL-2

Answer 50

produced by lymphoid and spleen cells formation stimulated by IL-1 stimulates growth and differentiation of lymphocytes

Question 51

IL-3

Answer 51

glycoprotein | stimulates growth and differentiation of lymphocytes

Question 52

GH effects on bone growth

Answer 52

1: widening of epiphyseal plate 2: growth of cartilage (chondrogenesis) 3: increased incorporation of sulphate into chondriotin sulphate and of proline into collagen 4: stimulates osteocyte activity => increased ossification most activity attributed to somatomedins, but has some direct effects

Question 53

TH effects on bone growth

Answer 53

1: stimulate cartilage breakdown and bone deposition - promote bone maturation/osteogenesis

Question 54

androgens in gone growth

Answer 54

responsible for pubertal growth spurt initially produces linear growth but then leads to increase in bone maturation and speed up closure of epiphyseal plate - cartilage formation can't keep up with bone deposition early maturation under influence of androgens => stunted growth some actions indirect via peptide growth factors

Question 55

estrogens on bone growth

Answer 55

inhibit bone growth | promote closure of epiphyseal plates

Question 56

insulin on bone growth

Answer 56

necessary, but role not known

Question 57

glucocorticoids on bone growth

Answer 57

direct action - inhibitory promote osteoporosis through decreased bone formation and increased bone resorption directly inhibit actions of somatomedins on bone