# SOMATOGENIC/LACTOGENIC HORMONES OF PLACENTA/PITUITARY

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1994 · $273,768

## Abstract

The genes of the human growth hormone/chorionic somatomammotropin (GH/CS)
gene cluster are expressed specifically in syncytiotrophoblastic
epithelium of the fetal placenta (hCS-A, hCS-B, hCS-L, and hGH-V) or in
somatotrope and somatolactotrope cells of the anterior pituitary (hGH-N).
The overall aims of this research program are to define the basis for the
high-level, tissue-specific, developmentally-controlled expression of this
gene cluster in vivo, to define the full spectrum of encoded protein
products, and to delineate the form and function of the cognate receptors
that mediate the tissue response to the encoded hormones. The SPECIFIC
AIMS of this proposal focus on: 1) Defining how the GH/CS gene locus is
organized at the level of chromatin structure, the mechanism and ontogeny
of its activation via its locus control region (LCR), the organization and
function of its LCR and flanking regulatory elements, and how they result
in placenta- versus pituitary-specific expression. As a corollary, a
survey of GH-deficient human patients may determine whether genetic
mutations of the LCR can result in human disease; 2) Establishing novel
pituitary cell lines that can serve as critical reagents for the
definition and characterization of the LCR, by targeted immortalization of
somatotrope cells in mice transgenic for the GH locus and LCR; 3)
Establishing a transgenic mouse model in which the entire GH/CS gene
cluster with its LCR and flanking regulatory components can be studied in
detail in their native configuration in vivo; 4) Characterizing the
structure and function of the alternatively-spliced, exon 3 deficient hGH
receptor isoform normally expressed in placental villi, and its potential
role in placental growth and development; and 5) Characterizing the
expression of the alternatively-processed transcripts and protein products
of the two least characterized genes in the cluster: hGH-V and hCS-L. The
methods used to achieve these aims include standard techniques of
molecular biology, transgenic mouse technology including targeted
oncogenesis, detection of clones in yeast artificial chromosome libraries
and their analysis and expression, cell culture and transfection,
microinjection of Xenopus oocytes, and protein analysis with gels and
antisera. The significance of this line of investigation will be the
detailed understanding of the expression and action of the GH/CS cluster
and its regulation as a unit by the LCR. This will serve as a foundation
for a sophisticated understanding of the pathophysiology of human growth
and development, and may lead in turn to the design of new means of
medical intervention.

## Key facts

- **NIH application ID:** 2199416
- **Project number:** 2R01HD025147-06
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** NANCY E. COOKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $273,768
- **Award type:** 2
- **Project period:** 1989-05-01 → 1998-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199416

## Citation

> US National Institutes of Health, RePORTER application 2199416, SOMATOGENIC/LACTOGENIC HORMONES OF PLACENTA/PITUITARY (2R01HD025147-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199416. Licensed CC0.

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