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PMID: 8631293 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gsh-1, an orphan Hox gene, is required for normal pituitary development.

The EMBO journal ·Vol. 15 ·No. 4 ·1996-02-15 ·Pages 714-24

Li H, Zeitler PS, Valerius MT, Small K, Potter SS

Abstract

The anterior pituitary regulates the function of multiple organ systems as well as body growth, and in turn is controlled by peptides released by the hypothalamus. We find that mutation of the Gsh-1 homeobox gene results in pleiotropic effects on pituitary development and function. Homozygous mutants exhibit extreme dwarfism, sexual infantilism and significant perinatal mortality. The mutant pituitary is small in size and hypocellular, with severely reduced numbers of growth hormone- and prolactin-producing cells. Moreover, the pituitary content of a subset of pituitary hormones, including growth hormone, prolactin and luteinizing hormone, is significantly decreased. The hypothalamus, although morphologically normal, is also perturbed in mutants. The gsh-1 gene is shown to be essential for growth hormone-releasing hormone (GHRH) gene expression in the arcuate nucleus of the hypothalamus. Further, sequence and electrophoretic mobility shift data suggest the Gsh-1 and GHRH genes as potential targets regulated by the Gsh-1-encoded protein. The mutant phenotype indicates a critical role for Gsh-1 in the genetic hierarchy of the formation and function of the hypothalamic-pituitary axis.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Gene Expression Regulation, Developmental Genes Genes, Homeobox Growth Hormone-Releasing Hormone/genetics Hematopoiesis Homeodomain Proteins/physiology Mice Mice, Knockout Molecular Sequence Data Pituitary Gland, Anterior/embryology Pituitary Hormones/metabolism RNA, Messenger/genetics Saccharomyces cerevisiae
Chemicals
Gsh1 protein, mouse Homeodomain Proteins Pituitary Hormones RNA, Messenger Growth Hormone-Releasing Hormone
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Li H
Department of Pediatrics, University of Cincinnati College of Medicine, OH 45229-3039, USA.
Zeitler P S
Valerius M T
Small K
Potter S S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-02-15
Pages
714-24
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450270
Subset
IM
Grants
NICHD NIH HHS · NIH HD 29599 · United States
External Links
PubMed source PMC Full Text View journal details
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