# ACTION OF INSULIN LIKE GROWTH FACTORS ON BONE

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF SAN FRANCISCO · 1987 · $207,203

## Abstract

The long term objective is to decrease the incidence of fractures in
elderly patients with postmenopausal (type 1) or aging (type 2)
osteophorosis.  This will be achieved by gaining a better basic
understanding of how growth factors effect bone formation and their
relationship to age-related bone loss.

The project will investigate the insulin-like growth factors (which are
also called somatomedins because they mediate the growth-promoting effect
of growth hormone).  The insulin-like growth factors (IGFs) are potent
cellular mitogens that directly stimulate bone growth.  The rationale for
studying IGFs is because they are presently the only hormones known that
can produce a graded growth-response in bone, and the plasma level of IGFs
and sensitivity of other mesenchymal tissues to IGFs decrease with aging.

The in vivo studies will use the perfused rat hind limb as a model to
achieve local as opposed to systemic biologic action of the hormones under
investigation.  IGFs alone and in combination with other calcium regulating
hormones (1,25(OH)2D3, PTH, cortisol and GH) will be continually infused by
Osmotic Minipumps into the femoral artery of adult and aging rats for 7 to
14 days.  Normal, calcium deficient, and partially vitamin D deficient rats
will be used.

The effects of these manipulations on bone growth as a function of age will
be measured by histomorphologic techniques that include double tetracycline
labeling.  The uninfused side will serve as the control.  The systemic
level of test hormones will be determined by radioimmunoassays and
competitive binding assays.

The possibility that other hormones in addition to cortisol affect
osteoblast function(s) by modulating IGF receptor status will be
investigated using cultured chick osteoblasts in serum free medium.  IGF
receptor types 1 and 2 will be determined by the specific binding of
iodinated IGF-I and -II, and the pattern of competitive binding with IGF-I,
IGF-II and insulin.  Receptors will be characterized by classic Scatchard
analysis.  The effect of PTH, calcitriol, 24,(25)OH2,D3, cortisol, and GH
on IGF receptors will be correlated with their actions on IGF-stimulated
DNA, collagen and noncollagen protein synthesis.

## Key facts

- **NIH application ID:** 3157222
- **Project number:** 5R01AR035496-03
- **Recipient organization:** CHILDREN'S HOSPITAL OF SAN FRANCISCO
- **Principal Investigator:** E M SPENCER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $207,203
- **Award type:** 5
- **Project period:** 1985-09-30 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157222

## Citation

> US National Institutes of Health, RePORTER application 3157222, ACTION OF INSULIN LIKE GROWTH FACTORS ON BONE (5R01AR035496-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157222. Licensed CC0.

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