# PARATHYROID HORMONE-LIKE PEPTIDE FROM KERATINOCYTES

> **NIH NIH R01** · YALE UNIVERSITY · 1988 · $131,120

## Abstract

Normal human keratinocytes in vitro make a molecule that appears to bind to
the parathyroid hormone receptor and stimulates the accumulation of
cyclic-AMP (cAMP) in rat osteosarcoma cells.  The molecule is not
parathyroid hormone itself, but shares many properties with one group of
PTH-like polypeptides responsible for the clinical syndrome of humoral
hypercalcemia of malignancy (HHM).  The aims of this proposal are to purify
the keratinocyte factor, determine its structure, and characterize its
biological activities.  The project has three parts:  Production of the
factor:  The first goal will be to define culture conditions which maximize
human keratinocyte production of the PTH-like factor.  The ultimate goal is
to produce at least 10 Mug/week of the factor in keratinocyte-conditioned
medium.

Purification and biochemical characterization:  A purification scheme
similar to that already described for tumor-derived PTH-like factors will
be used for purification.  In brief, this employs a series of steps
including concentration by ultra-filtration, molecular sieve
chromatography, hydrophobic interaction chromatography, isoelectric
focusing, and high-performance liquid chromatography.  Highly purified
material will be used as immunogen, and when sufficient amounts of
homogeneous material are available, we will obtain a partial amino acid
sequence.

Biological activity:  While definitive studies of the biological action of
this keratinocyte factor must await its purification, knowledge of its
PTH-like activity allows us to generate testable hypotheses.  Thus, we
hypothesize that the keratinocyte factor should have significant local or
distant biological effects by virtue of its ability to bind to the PTH
receptor and increase intracellular cyclic-AMP.  We plan to test this
hypothesis by examining the effect of PTH on keratinocyte growth and
differentiation as well as the effect of purified KCM factor on other
PTH-sensitive systems such as in vitro bone resorption.

Long-range goals of this proposal are:  1) to better understand
keratinocyte homeostasis and the role of locally produced, biologically
active molecules in common disorders of keratinocyte homeostasis, such as
psoriasis; 2) to better understand how factors produced outside the
parathyroid gland modulate calcium and Vitamin D metabolism in health and
disease.

## Key facts

- **NIH application ID:** 3158232
- **Project number:** 5R01AR037594-03
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** LEONARD M MILSTONE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $131,120
- **Award type:** 5
- **Project period:** 1986-08-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158232

## Citation

> US National Institutes of Health, RePORTER application 3158232, PARATHYROID HORMONE-LIKE PEPTIDE FROM KERATINOCYTES (5R01AR037594-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158232. Licensed CC0.

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