Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells.

Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Research Abstract Details 

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Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Abstract Text:

Adam C Buser,Elizabeth K Gass-Handel,Shannon L Wyszomierski,Wolfgang Doppler,Susan A Leonhardt,Jerome Schaack,Jeffrey M Rosen,Harriet Watkin,Steven M Anderson,Dean P Edwards,

Prolactin (PRL) and glucocorticoids act synergistically to stimulate transcription of the beta-casein milk protein gene. Signal transducer and activator of transcription 5 (Stat5) mediates PRL-dependent trans-activation, and glucocorticoid potentiation occurs through cross talk between glucocorticoid receptor (GR) and Stat5 at the beta-casein promoter. In the mouse, progesterone withdrawal leads to terminal differentiation and secretory activation of the mammary gland at parturition, indicating progesterone's role in repressing milk protein gene expression during pregnancy. To investigate the mechanism of the inhibitory action of progesterone, experiments were performed with cell culture systems reconstituted to express progesterone receptor (PR), the PRL receptor/Stat5 signaling pathway, and GR, enabling evaluation of PR, GR, and Stat5 interactions at the beta-casein promoter. With COS-1, normal murine mammary gland, HC-11, and primary mammary epithelial cells, progestin-PR directly repressed the PRL receptor/Stat5a signaling pathway's mediation of PRL-induced beta-casein transcription. Progestin-PR also inhibited glucocorticoid-GR enhancement of PRL induced trans-activation of beta-casein. Inhibition depended on a functional PR DNA binding domain and specific PR-DNA interactions at the beta-casein promoter. Chromatin immunoprecipitation assays in HC-11 cells revealed recruitment of PR and Stat5a to the beta-casein promoter by progestin or PRL, respectively. Recruitment was disrupted by cotreatment with progestin and PRL, suggesting a mutual interference between activated PR and Stat5a. Without PRL, progestin-PR also recruited Stat5a to the beta-casein promoter, suggesting that recruitment of an unactivated form of Stat5a may contribute to inhibition of beta-casein by progesterone. These results define a negative cross talk between PR and Stat5a/GR that may contribute to the physiological role of progesterone to repress lactogenic hormone induction of the beta-casein gene in the mammary gland during pregnancy.

Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Publishing Authors By Initials

AC Buser,EK Gass-Handel,SL Wyszomierski,W Doppler,SA Leonhardt,J Schaack,JM Rosen,H Watkin,SM Anderson,DP Edwards,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular endocrinology (Baltimore, Md.)

VOLUME: 21

Page Numbers: 106-25

Journal Abbreviation: Mol. Endocrinol.

ISSN: 0888-8809

DAY: 14

MONTH: 09

YEAR: 2006

Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8801431

Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Information

Substance Name: Prolactin

Registry Number: 9002-62-4

Grant and Affiliation Information for Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells.

AFFILIATION: Department of Pathology, University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA.

Country: United States

AGENCY: United States NICHD

GRANT: HD038129

ACRONYM: HD

MEDLINETA: Mol Endocrinol

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