STRUCTURE AND FUNCTION OF GROWTH HORMONE-RELATED GENES

  • Eberhardt, Norman L, (PI)

Project: Research project

Description

The genes for growth hormone (GH), chrionic somatomammotropin (CS) and
prolactin (Prl) are a family of structurally related genes which have
evolved from a common precursor via gene duplication and are essential for
normal mammalian growth and development. The genes are regulated by
thyroid and glucocorticoid hormones and represent an important family of
genes whose study will aid in understanding hormone action and
tissue-specific expression. Our goal is to establish a complete structural
and topological analysis of this gene family to provide a foundation for
analysis of the expression, hormonal regulation and evolution of this gene
family. The genes for human (h) GH and CS form a multigene family which is
linked on ca. 100 kb of DNA on chromosome be ordered topologically; the
localization and sequence of the interspersed repetitive DNA sequences will
be established. The linker regions between hCS and hGH will be sequenced
to determine if specific structures related to gene duplication exist. The
genomic sequences for hGH and hCS will be extended in the 5 feet and 3 feet
direction and their semonal regulation, and tissue-specific expression of
these genes. The various hGH and hCS promoters will be compared in
cell-free transcription systems to assess the functionality of the genes.
Individual hGH and hCS genes will be expressed utilizing SV40 and/or bovine
papilloma virus vectors; the products will be tested for binding to growth
hormone receptors and biological activity to determine the functional
significance of the individual genes; the hormonal regulation of the hGH
and hCS genes will be assessed after gene transfer. DNA from human dwarfs
and individuals lacking immunoreactive CS will be analyzed by Southern
analysis for the presence of deletions or mutations and for linkage to
other functions such as growth hormone receptor defects which may yield
insinght into gene function. Finally, nuclease sensitivity studies and
determinations of methylation patterns for hGH and hCS genes in placenta
and pituitary tumors and the binding of nuclear proteins to the hGH and hCS
genes will be performed to determine potential factors involved in the
tissue specific expression of this gene family.
StatusFinished
Effective start/end date1/1/8412/31/86

Funding

  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Growth Hormone
Genes
Gene Duplication
Laron Syndrome
Hormones
Gene Expression
Human Growth Hormone
Sequence Deletion
Nucleic Acid Repetitive Sequences
DNA
Pituitary Neoplasms
Multigene Family
Nuclear Proteins
Growth and Development
Methylation
Glucocorticoids
Carrier Proteins
Chromosomes
Viruses

ASJC

  • Medicine(all)