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Epidermal growth factor and phorbol ester regulate prolactin gene expression via distinct pathways.

A E Jackson¹, S K Bandyopadhyay, C Bancroft

¹Department of Physiology and Biophysics, Mount Sinai School of Medicine of City University of New York, NY 10029.

Molecular and Cellular Endocrinology

|February 12, 1990

Summary

Epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) influence prolactin (PRL) gene expression through distinct pathways. This study reveals that EGF and TPA utilize partially non-overlapping gene-distal intermediates for their effects on PRL gene expression.

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Area of Science:

Endocrinology
Molecular Biology
Cell Signaling

Background:

Epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) have been suggested to impact prolactin (PRL) gene expression similarly in pituitary cells.
The specific gene-distal signaling intermediates mediating these effects remain largely uncharacterized.

Purpose of the Study:

To investigate whether the actions of EGF and TPA on prolactin gene expression involve common gene-distal intermediates.
To differentiate the signaling pathways utilized by EGF and TPA in regulating PRL gene expression.

Main Methods:

GH3 pituitary cells were utilized to assess the effects of EGF and TPA on PRL gene expression.
Cells were chronically exposed to TPA to down-regulate protein kinase C activity.

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Transient expression assays using a PRL promoter construct ((-187)PRL-CAT) and measurement of endogenous PRL mRNA accumulation were performed.

Main Results:

Chronic TPA exposure inhibited acute TPA-stimulated PRL promoter activity but did not affect EGF-stimulated PRL mRNA accumulation or promoter activity.
The acute stimulatory effects of EGF and TPA on the PRL promoter construct were additive.
These findings indicate distinct signaling mechanisms for EGF and TPA.

Conclusions:

EGF and TPA employ at least partially non-overlapping gene-distal intermediates to regulate prolactin gene expression.
The signaling pathways activated by EGF and TPA in GH3 cells are distinct, despite potential similarities in overall effects on PRL expression.