# RICKETS AND OSTEOMALACIA

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 1993 · $213,993

## Abstract

When compared to Old World primate species, New World primates reared in
captivity exhibit an inordinately high incidence of rickets and
osteomalacia.  The disease is indistinguishable from vitamin D deficiency,
but occurs in the presence of extraordinarily high, not low, blood levels
of the vitamin D hormone, 1,25-dihydroxyvitamin D3 (l,25-(OH)2D3). This
finding infers a state of "resistance" to the hormone.  We have discovered
that this "resistant state" is not due to a defect in the receptor protein
for l,25-(OH)2D3 (VDR) but rather is due to the presence of an
intracellular protein (IDBP) that competitively binds l,25-(OH)2D3 and
effectively inhibits its ability to bind to the VDR.  IDBP also binds
other steroids hormones, and it is likely responsible for the "global"
nature of steroid resistance in New World primates.  The aim of the
proposed research is two-fold. The first objective is to purify the IDBP,
determine part of its protein sequence, and clone the complementary DNA
(cDNA) which codes for the protein.  We will accomplish purification of
IDBP by a series of chromatographic steps and by protein gel
electrophoresis.  We will clone the cDNA from a library of cDNAs developed
from messenger RNA (mRNA) extracted from the cells of a vitamin D-
resistant New World primate.  The second objective is to determine the
function of this protein in New World primate cells.  Using a variety of
biochemical, molecular, and cell biology techniques we will investigate
how expression IDBP results in the steroid/sterol hormone-resistant
phenotype.  We anticipate the results of this work will: l) uncover a
previously unrecognized layer of control for modulation of cellular
steroid hormone-receptor interaction; 2) provide important clues as why
most New World species developed and maintained a form of compensated
target-tissue resistance to steroid hormones; 3) help us understand new
ways in which steroid/sterol hormone metabolism can be altered in
primates, including man, to meet the needs of the host; and 4) provide a
explanation for human steroid hormone-resistant states not associated with
mutations in the steroid receptor genes.

## Key facts

- **NIH application ID:** 3158109
- **Project number:** 2R01AR037399-07
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **SAM.gov UEI:** NCSMA19DF7E6
- **Principal Investigator:** John S Adams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $213,993
- **Award type:** 2
- **Project period:** 1990-01-01 → 1997-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158109

## Citation

> US National Institutes of Health, RePORTER application 3158109, RICKETS AND OSTEOMALACIA (2R01AR037399-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158109. Licensed CC0.

---

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