Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth

Robert E Hammer, Ralph L. Brinster, Michael G. Rosenfeld, Ronald M. Evans, Kelly E. Mayo

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

The neurohumoral regulation of growth hormone secretion is mediated in part by two hypothalamic peptides that reach the anterior pituitary via the hypothalamo-hypophysial portal blood system1. Somatostatin inhibits the release of growth hormone2, whereas growth hormone-releasing factor (GRF) positively regulates both growth hormone synthesis3,4 and secretion5,6. Two forms of human GRF, 40 and 44 amino acids long, have been characterized from extra-hypothalamic tumours7,8 as well as from the hypothalamus9. Analysis of human GRF complementary DNA10,11 and genomic12 clones indicates that the GRF peptides are first synthesized as a 107- or 108-amino-acid precursor protein. To examine the physiological consequences of GRF expression, we have established strains of transgenic mice containing a fusion gene including the promoter/regulatory region of the mouse metal-lothionein-I (MT-I) gene 13 and the coding region of the human GRF gene12. We report that expression of the human GRF precursor protein in these animals results in measurable levels of human GRF and increased levels of mouse growth hormone in plasma and accelerated growth rates relative to control littermates. These results demonstrate a direct role for GRF in the positive regulation of somatic growth. Unexpectedly, female transgenic mice carrying the MT-GRF fusion gene are fertile, in contrast to female transgenic mice expressing human or rat growth hormone, which are generally infertile. These transgenic mouse strains should provide useful animal models for the study of several types of human growth disorders.

Original languageEnglish (US)
Pages (from-to)413-416
Number of pages4
JournalNature
Volume315
Issue number6018
DOIs
StatePublished - 1985

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Growth Hormone-Releasing Hormone
Human Growth Hormone
Transgenic Mice
Growth
Growth Hormone
Protein Precursors
Gene Fusion
Growth Disorders
Amino Acids
Nucleic Acid Regulatory Sequences
Somatostatin
Genetic Promoter Regions
Animal Models
Clone Cells
Metals

ASJC Scopus subject areas

  • General

Cite this

Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth. / Hammer, Robert E; Brinster, Ralph L.; Rosenfeld, Michael G.; Evans, Ronald M.; Mayo, Kelly E.

In: Nature, Vol. 315, No. 6018, 1985, p. 413-416.

Research output: Contribution to journalArticle

Hammer, Robert E ; Brinster, Ralph L. ; Rosenfeld, Michael G. ; Evans, Ronald M. ; Mayo, Kelly E. / Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth. In: Nature. 1985 ; Vol. 315, No. 6018. pp. 413-416.
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