Unit 4.1 Day 24 Learning objectives

growth

direct development characteristics

same pattern

increase in size

indirect development characteristics

metamorphosis

determinant growth

mammals

reach a max size

indeterminant growth

fish

continue to grow throughout life

history of GH research

assays w/ radioactive sulfate (35^SO4) into epiphyseal cartilage of long bones

bones → bone makeup → GH vs IGF

cellular growth types

hypertrophy: inc in size

hyperplasia: inc in number

extraceullar matrix (ECM) growth

cell cycle steps

interphase

mitotic

interphase steps

g1

s

g2

g0

mitotic steps

mitosis

cytokinesis

GH axis

regulators of the GH axis: stimulators

regulators of the GH axis: inhibitors

growth hormones

growth hormone (GH)

insulin-like growth factor (IGF)

somatostatin (SS)

insulin

thyroid hormones (TH)

growth hormone (GH) produced by

somatotroph cells in adenohypophysis

growth hormone (GH) structure

191 aa

2 intramolecular disulfide bonds

1 tryptophan

growth hormone (GH) common mechanism of action

Jak/Stat signaling

insulin-like growth factor (IGF) overview

somatomedins

IGF-I and IGF-II

IGF-I structure

70 aa

post-natal growth

IGF-I receptor

receptor tyrosine kinase (RTK)

(linked to IRS, Akt, MAPK)

IGF-II structure

76 aa

embryonic growth

IGF-II receptor

atypical receptor and signaling

insulin-like growth factor (IGF) mechanisms of action

cognate receptors

• BUT -1 + -2 can bind each others at high concentrations

• INS can bind IGFR at high concentrations

inhibit adenylyl cyclase activity: liver, spleen, adipose, lymphocytes

IRS/PI3K/Akt, MAPK

stims. SS release from hypothalamus

somatostatin structure

14 residues (variable)

well conserved (vertebrates)

somatostatin synth/secre. by

wide variety of tissues

insulin functions

glucose transport systems

glycogen synthesis

cell growth (proliferation)

insulin used for

full GH/IGF stimulated growth (permissive)

energy for cells w/ glucose uptake

uptake of aa

thyroid hormone synthesis

T3/T4 structure

4I = T4 ( thyroxine, tetraiodothyronine)

3I = T3 (triiodothyronine)

thyroid hormones used for

GH/IFG stimulated growth (permissive)

T3/4 both required

thyroid hormones stimulates

GH synth + secretion

(GH levels diminish w/out TH)

other growth factor hormones

neurotropic growth factors

epithelial growth factor (EGF)

platelet-derived growth factor (PDGF)

angiogenic factors

hematopoietic growth factors

cytokinins

neurotropic growth factors functions

NGF: targets neuronal cells (development, growth, + fx)

tavset-derived neurotropic factor

hematopoietic growth factors types

erthyropoietin

thymosins

erthyropoietin function

increase RBC

thymosins function

increase WBC (esp. lymphocytes)