# PARATHYROID HORMONE-LIKE PEPTIDE FROM KERATINOCYTES

> **NIH NIH R01** · YALE UNIVERSITY · 1991 · $235,955

## Abstract

Normal human keratinocytes secrete a parathyroid hormone-like peptide
(PTH-LP) in vitro. The keratinocyte PTH-LP appears to be derived from the
same gene as the recently cloned cDNA for a tumor-derived PTH-LP
associated with the clinical syndrome of humoral hypercalcemia of
malignancy. The normal function of this peptide is not known: the factors
regulating its expression in vivo are not known.

The long-term objectives of this proposal are: 1) to determine whether
and how production of this molecule is regulated in keratinocytes; 2) to
identify the function(s) of this molecule in the skin and elucidate the
mechanism(s) by which it acts: 3) to determine whether there is a
relationship between diseases of the skin and abnormal expression of this
molecule.

These aims and hypotheses will be investigated in tissue sections and in
tissue culture models of epidermal growth and differentiation and will
employ specific molecular and immunologic probes for the PTH-LP. The
specific questions are: Production regulations: a. Which keratinocyts
within the epidermis make and secrete the PTH-LP? b. Are there
physiologic or pharmacologic ways to regulate production of the PTH-LP by
keratinocytes? c. What is the molecular basis of regulated production? Is
production regulated at the level of transcription, splicing,
translation, intracellular processing or secretion? Function/mechanism of
action: a. What effect does the PTH-LP have on normal keratinocyte growth
and differentiation and what mediates that effect? Hypothesis: The
autocrine action of the PTH-LP acts via an increase in intracellular
calcium which then triggers or augments differentiation. b. What  are its
effects on dermal fibroblasts? Hypothesis: The molecule plays a role in
dermal remodelling via its TGF-b like action on secretion on connective
tissue elements. Relation to disease: a. Is the PTH-LP overexpressed in
neoplastic diseases of the epidermis or in benign hyperproliferative
diseases? If so, is the PTH-LP detectable in the serum? b. If the
molecule has a role in normal keratinization, are there disorders of
keratinization caused by abnormal production of or response to the PTH-
LP?

## Key facts

- **NIH application ID:** 3158234
- **Project number:** 5R01AR037594-06
- **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:** 1991
- **Award amount:** $235,955
- **Award type:** 5
- **Project period:** 1988-08-01 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158234

## Citation

> US National Institutes of Health, RePORTER application 3158234, PARATHYROID HORMONE-LIKE PEPTIDE FROM KERATINOCYTES (5R01AR037594-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158234. Licensed CC0.

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