# EFFECTS OF HORMONES ON BONE RESORPTION IN VITRO

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1992 · $213,424

## Abstract

The overall goal of this research is to extend our understanding of
the mechanisms of action of hormones on bone.  The approaches
include a) biochemical studies of second messenger pathways in
bone and changes in these pathways in response to calcemic
hormones and b) pharmacological studies utilizing agents that
affect these metabolic pathways in other tissues to determine
their influence on bone resorption.

The proposed studies would examine the functional significance of
effects of parathyroid hormone (PTH) and other calcemic
hormones on bone phospholipid metabolism.  Studies to date
indicate that concentrations of PTH and thrombin that are
equieffective in stimulating resorption in vitro show marked
differences their stimulation of inositol phosphate production,
thrombin being the more effective agent.  The proposed studies
would further examine the effects of PTH and thrombin on bone
phospholipid and calcium metabolism.  Changes in inositol
phosphates, inositol phospholipids, and diacylglycerol would be
more fully characterizes in bone organ cultures, normal bone cells
and osteosarcoma-derived cells.  The cells would also be used to
determine whether these agents differ in their effects on
intracellular calcium.  Possible bases for the observed differences
in inositol phosphate production would be explored, including
altered phosphatase activity, and the relative increases in cyclic
AMP elicited by PTH and thrombin.  The possibility that the
changes in inositol phosphates are related to bone formation
rather than resorption will be examined.  Studies similar to those
carried out with PTH and thrombin would be extended to other
stimulators of resorption, including growth factors and cytokines.
Pharmacological agents whose effects on resorption could be due
to altered cellular calcium metabolism (e.g. tamoxifen,
cyclosporine, and milrinone) will be tested for their effects on the
Ca/phosphatidylinositol pathway.  Agents shown to affect the
pathways of phosphatidylinositol metabolism and protein kinase C
(including RO 59 022 and bryostatin) will be examined for their
effects on bone resorption and formation.  Upgrading of presently
available HPLC capabilities would permit measuremnt of newly
recognized and potentially important inositol phosphate
metabolites.  The described studies should increase our
understanding of the role of the calcium second messenger
systems in the action of hormones on bone.

## Key facts

- **NIH application ID:** 3154741
- **Project number:** 5R01AR011262-26
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** PAULA H STERN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $213,424
- **Award type:** 5
- **Project period:** 1978-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154741

## Citation

> US National Institutes of Health, RePORTER application 3154741, EFFECTS OF HORMONES ON BONE RESORPTION IN VITRO (5R01AR011262-26). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3154741. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*