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Insulin and cyclic adenosine monophosphate increase prolactin gene expression through different response pathways
1Department of Medicine, New York University Medical Center, NY 10016, USA.
Molecular and Cellular Endocrinology
|April 1, 1995
Summary
Insulin and cyclic AMP (cAMP) independently stimulate prolactin gene transcription in pituitary cells. While they may use similar DNA sequences, their signaling pathways are distinct, offering insights into gene regulation.
Area of Science:
- Endocrinology
- Molecular Biology
- Gene Regulation
Background:
- Prolactin gene expression is crucial for various physiological functions.
- Understanding the regulation of prolactin gene transcription by hormones like insulin and signaling molecules like cAMP is vital.
Purpose of the Study:
- To investigate the independent and combined effects of insulin and cAMP on prolactin gene transcription.
- To elucidate the signaling pathways mediating the actions of insulin and cAMP on the prolactin gene.
Main Methods:
- Utilized a prolactin-CAT reporter construct (pPrl(-173/+75)CAT) in rat pituitary tumor GH cells.
- Assessed gene expression changes in response to insulin, cAMP, and their combination.
- Performed experiments to differentiate the signaling pathways, including measuring cAMP levels and using inhibitors of cAMP-dependent protein kinase A.
Main Results:
- Both insulin and cAMP individually stimulated prolactin-CAT expression 10- to 30-fold.
- Combined insulin and cAMP treatment resulted in an additive 20- to 60-fold stimulation.
- Evidence suggests that insulin and cAMP may act through identical regulatory sequences (-106/-87 region) but via independent signaling pathways.
Conclusions:
- Insulin and cAMP independently regulate prolactin gene transcription in pituitary cells.
- Despite potentially shared regulatory DNA sequences, their intracellular signaling mechanisms are distinct.
- These findings highlight the complex and divergent pathways controlling prolactin gene expression.