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Cell lines of the pituitary gonadotrope lineage derived by targeted oncogenesis in transgenic mice
J J Windle1, R I Weiner, P L Mellon
1Regulatory Biology Laboratory, Salk Institute, La Jolla, California 92037.
Abstract:
Study of the molecular and cellular biology of the gonadotropin hormones would be greatly facilitated by the availability of immortalized anterior pituitary gonadotrope cell lines. We directed expression of the simian virus-40 (SV40) T-antigen (Tag) oncogene to specific cells in the anterior pituitary of transgenic mice using the promoter/enhancer region from the human glycoprotein hormone alpha-subunit gene. Transgenic mice carrying this fusion gene developed anterior pituitary tumors. Clonal cell lines established from these tumors express the endogenous mouse alpha-subunit gene and synthesize and secrete alpha-subunit protein. However, they do not express beta-subunit genes. Alpha-subunit mRNA is induced by GnRH in a dose- and time-dependent manner, but is not regulated by TRH. Thus, we have targeted tumorigenesis in transgenic mice to anterior pituitary cells of the gonadotrope lineage to immortalize this specific endocrine cell while maintaining several highly differentiated functions unique to gonadotropes.
Insights
Scientists created immortalized gonadotrope cell lines from mouse tumors. These cells express alpha-subunit, crucial for gonadotropin hormones, and are vital for studying hormone regulation.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Immortalized cell lines are essential for studying gonadotropin hormones.
- Previous methods lacked specific cell targeting for gonadotrope research.
Purpose of the Study:
- To develop immortalized anterior pituitary gonadotrope cell lines.
- To investigate the regulation of alpha-subunit gene expression in these cells.
Main Methods:
- Utilized transgenic mice with targeted SV40 T-antigen oncogene expression.
- Employed the human glycoprotein hormone alpha-subunit gene promoter/enhancer region.
- Established and characterized clonal cell lines from anterior pituitary tumors.
Main Results:
- Transgenic mice developed anterior pituitary tumors.
- Established cell lines express endogenous mouse alpha-subunit gene and secrete alpha-subunit protein.
- Alpha-subunit mRNA levels increased with GnRH stimulation in a dose- and time-dependent manner.
- Cell lines did not express beta-subunit genes.
Conclusions:
- Successfully immortalized anterior pituitary gonadotrope cells using targeted oncogene expression.
- These cell lines retain differentiated functions, including alpha-subunit expression and GnRH responsiveness.
- The developed cell lines are valuable tools for studying gonadotropin hormone biology.