# CALCITROPIC HORMONES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1992 · $185,612

## Abstract

DESCRIPTION (Adapted from the Applicant's Abstract):  This application is
designed to study the regulatory interactions between the calcitropic
hormones and Chromogranin A (CgA).  The general hypothesis is that CgA and
its processed peptides interact at the level of gene expression,
post-translational processing, and secretion with the calcitropic hormones,
namely:  (a) the peptides encoded by the calcitonin (CT) gene(s),
especially CT itself and CGRP (calcitonin-gene-relate-peptide); (b)
parathyroid hormone (PTH); and (c) the PTH-related protein (PTHrP)
associated with the hypercalcemia of malignancy.  This hypothesis is
derived from the studies with cell lines from calcitropic hormone-producing
endocrine tissues that also produce and secrete CgA.  Previous work has
demonstrated common regulatory pathways for CgA and the calcitropic
hormones in studies of mRNA expression, biosynthesis, and secretion with
these cell lines.  It has also been demonstrated by pulse-chase studies and
Western blotting, that CgA is processed to different peptides in a
tissue-specific manner by calcitropic hormone-producing cells.  The
experimental plan now proposes to study the molecular mechanisms of these
regulatory interactions.  For studies of CgA processing, pulse-chase and
Western studies will be continued with antibodies to CgA-peptides based on
the processing of the protein at its dibasic residues.  These studies,
along with analytical biochemical procedures, are intended to lead to the
identification of tissue-specific CgA-derived peptides for the different
cell lines.  In vivo and in vitro secretory studies of these peptides will
be conducted to further evaluate their biological relevance.  For studies
of gene expression, efforts will identify the regulatory sequences of the
CgA gene by genomic cloning, restriction mapping, and DNA sequencing.
Further studies will include investigation of the promoter and enhancer
functions of these regulatory elements with reporter genes such as in the
CAT assay.  Such CAT assays will be performed in different cell types to
evaluate the tissue specificity of CgA regulation.  The hormone- and second
messenger-responsiveness of these regulatory elements will be evaluated by
studying the effects of the calcitropic hormones themselves, and relevant
second messengers such as cAMP and calcium.  These transcription units can
be compared to known hormone-specific transcription units.  It may thus be
possible to discern those structural features of CgA DNA regulatory
sequences that are unique and those that they share with the calcitropic
proteins and peptides, and thus elucidate such mechanisms of regulatory
interactions for CgA and the calcitropic hormones.

## Key facts

- **NIH application ID:** 3154857
- **Project number:** 5R01AR015888-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** LEONARD JOHN DEFTOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $185,612
- **Award type:** 5
- **Project period:** 1976-05-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154857

## Citation

> US National Institutes of Health, RePORTER application 3154857, CALCITROPIC HORMONES (5R01AR015888-19). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154857. Licensed CC0.

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