# HORMONAL MODULATION OF BONE ADENYLATE CYCLASE

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1987 · $147,693

## Abstract

The long-term objectives of this research is to understand the
mechanisms by which glucocorticoid hormone excess, thyroid
hormone excess and estrogen deficiency lead to osteopenia and
magnesium deficiency leads to skeletal resistance to resorptive
stimuli.  In the proposed study we will test the hypothesis that
these conditions induce changes in the regulatory properties of
bone adenylate cyclase.  Approximately two-thirds of this
investigation will involve the detailed characterization of the
adenylate cyclase present in membranes obtained from bones of
normal adult guinea pigs.  This will entail:  1) determination of
the effects of PTH, isoproterenol, and prostaglandin E2, agonists
which activate bone adenylate cyclase, on the Ka for Mg++ and on
the Ki for calcium of the high and low affinity calcium inhibition
sites previously identified in the enzyme complex; 2)
identification of the sites within the enzyme complex where Mg++
binding activation occurs; and 3) identification of the sites within
the enzyme complex where Ca++ binding inhibits adenylate
cyclase activity and investigation of the mechanism by which
Ca++ inhibition occurs.  Reconstitution methodology employing
plasma membranes from turkey erythrocytes and S49 cyc-murine
lymphoma cells and cholate extracts from bone membranes will
be used in these latter two studies.  The possible role of the
inhibitory guanine nucleotide regulatory protein, Ni, in the
calcium inhibition of the adenylate cyclase will also be evaluated.
Bone membranes will be pretreated with pertussis toxin to
inactivate Ni and the parameters of calcium inhibition of the
adenylate cyclase activity in the treated membranes compared to
control membranes.  Once this baseline data has been obtained,
the regulatory characteristics of adenylate cyclase with respect
to Mg++ and agonist activation and Ca++ inhibition will be
examined in bone membranes obtained from animals exposed in
vivo to:  1) glucocorticoid excess, 2) thyroid hormone excess, 3)
estrogen deficiency, and 4) magnesium deficiency.  In addition,
the effects of glucocorticoid or thyroid hormone excess and
estrogen on magnesium deficiency on the relative amounts of the
stimulatory and inhibitory guanine nucleotide regulatory proteins,
Ns and Ni, in the bone membranes will be determined.

## Key facts

- **NIH application ID:** 3158077
- **Project number:** 1R01AR037350-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** ROBERT K RUDE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $147,693
- **Award type:** 1
- **Project period:** 1987-08-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158077

## Citation

> US National Institutes of Health, RePORTER application 3158077, HORMONAL MODULATION OF BONE ADENYLATE CYCLASE (1R01AR037350-01A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158077. Licensed CC0.

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