Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.
Abstract: The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.
Publication Date: 1992-05-01 PubMed ID: 1373809PubMed Central: PMC364386DOI: 10.1128/mcb.12.5.2143-2153.1992Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research focuses on understanding the molecular mechanisms that drive the development of different endocrine cell types in the pituitary gland. More specifically, it identifies a regulatory element important for the gonadotrope cell lineage, which produces hormones controlling reproductive functions.
Objective of the Study
To understand the various molecular mechanisms involved in the formation of different types of endocrine cells in the pituitary. Particular emphasis is given to gonadotropic cells, which produce reproductive hormones, and the specific proteins that regulate their development.
Methodology
- Transgenic mice and a newly developed gonadotrope cell line were used for experimentation.
- Through these, a regulatory element was identified that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene.
- A 54-kDa protein capable of binding to this element was also identified, purified, and characterized.
Findings
- A regulatory element that confers gonadotrope-specific expression was identified in the glycoprotein hormone alpha-subunit gene.
- It was found that a 54-kDa protein binds to this regulatory element. Notably, this protein is unique to gonadotrope lineage cells and is not the same as the Pit-1/GHF-1 protein known to be involved in the differentiation of somatotrope and lactotrope lineages in the pituitary.
- The research also discovered that the human and equine alpha-subunit genes are expressed in placental cells. However, the transcription factors TSEB and alpha-ACT, previously identified as important for placental expression, were not present in pituitary gonadotrope cells. This discovery points to distinct mechanisms regulating gene expression in these two different tissues.
Significance of the Research
- This research brings valuable new information to our understanding of the molecular mechanisms driving differentiation in pituitary cells.
- Understanding these mechanisms can also illuminate the functional nuances that govern hormone regulation in the reproductive system.
- The identification of tissue-specific factors can provide new targets for therapeutic intervention to treat various hormonal disorders.
Cite This Article
APA
Horn F, Windle JJ, Barnhart KM, Mellon PL.
(1992).
Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.
Mol Cell Biol, 12(5), 2143-2153.
https://doi.org/10.1128/mcb.12.5.2143-2153.1992 Publication
Researcher Affiliations
- Salk Institute, La Jolla, California 92037.
MeSH Terms
- Animals
- Base Sequence
- Cell Line
- Female
- Gene Expression
- Glycoprotein Hormones, alpha Subunit / genetics
- Horses
- Humans
- Mice
- Mice, Inbred Strains
- Mice, Transgenic
- Molecular Sequence Data
- Mutagenesis, Site-Directed
- Oligodeoxyribonucleotides
- Organ Specificity
- Pituitary Gland, Anterior / physiology
- Pituitary Neoplasms / genetics
- Placenta / physiology
- Plasmids
- Pregnancy
- Promoter Regions, Genetic
- Sequence Homology, Nucleic Acid
- Transcription Factors / metabolism
- Transfection
Grant Funding
- R01 HD020377 / NICHD NIH HHS
- CA14195 / NCI NIH HHS
- HD20377 / NICHD NIH HHS
- HD23818 / NICHD NIH HHS
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