# THE PHYSIOLOGY OF PLACENTAL LACTOGEN

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 1994 · $184,842

## Abstract

Studies from our laboratory during the past five years strongly suggest a
novel physiological role for apolipoprotein AI (apoAI) in the regulation of
the synthesis and secretion of human placental lactogen (hPL) during
pregnancy.  The stimulation of hPL synthesis in response to apoAI appears
to be due to stimulation of hPL gene expression.  Over the next five years,
we propose to extend our cellular and intracellular studies of the actions
of apoAI by examining the molecular mechanisms involved in apoAI-mediated
hPL gene expression.  Our specific goals are: (1).  To determine the
relative contributions of transcriptional and post-transcriptional
mechanisms in the stimulation of hPL mRNA levels in response to apoAI.
Nuclear run-on experiments will be used to determine the effects of apoAI
on hPL mRNA transcription, and studies of the half-life of hPL mRNA will be
used to determine the effect of apoAI on the degradation of hPL mRNA. (2).
To delineate the DNA element(s) in the promoter of the hPL gene necessary
for apoAI-mediated hPL expression.  The DNA element(s) will be determined
by examining the effects of different deletions in the hPL promoter on
expression of CAT (chloramphenicol acetyltransferase) activity in
choriocarcinoma cells transfected with vectors containing regions of the
hPL promoter. (3).  To determine the sequence of the cis-acting DNA
element(s) of the hPL promoter involved in apoAI-mediated hPL gene
expression.  Mobility gel shift and DNAse I footprinting assays will be
utilized to localize the specific nucleotide sequence of the DNA
element(s). (4).  To characterize the placental DNA binding protein(s)
(transcription factor(s)) involved in regulation of apoAI-mediated hPL gene
expression.  Initial studies will determine the molecular weight(s) and
N-terminal amino acid sequence(s) of the transcription factor(s).  Since
apoAI is the first factor known to stimulate a sustained increase in hPL
synthesis, delineation of the cis- and trans-acting factors involved in
apoAI-mediated gene expression should provide important insight into the
regulation of hPL gene expression.  Since recent studies also implicate
apoAI as a regulatory factor in other cell types, these studies may also
provide insight into the mechanisms by which apoAI affects gene expression
in other cells.

## Key facts

- **NIH application ID:** 2195689
- **Project number:** 5R01HD007447-20
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **SAM.gov UEI:** JZD1HLM2ZU83
- **Principal Investigator:** Stuart Handwerger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $184,842
- **Award type:** 5
- **Project period:** 1978-06-01 → 1997-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2195689

## Citation

> US National Institutes of Health, RePORTER application 2195689, THE PHYSIOLOGY OF PLACENTAL LACTOGEN (5R01HD007447-20). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2195689. Licensed CC0.

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