Ectopic ICER expression in pituitary corticotroph AtT20 cells

Effects on morphology, cell cycle, and hormonal production

Monica Lamas, Carlos Molina, Nicholas S. Foulkes, Erik Jansen, Paolo Sassone-Corsi

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

The products of the cAMP response element modulator (CREM) gene play an important role in the transcriptional response to cAMP in endocrine cells. By virtue of an alternative, intronic promoter within the gene, the inducible cAMP early repressor (ICER) isoform is generated. ICER was shown to act as a dominant negative regulator and to be cAMP-inducible in various neuroendocrine cells and tissues. ICER negatively autoregulates its own expression and has been postulated to participate in the molecular events governing oscillatory hormonal regulations. To elucidate ICER function in pituitary physiology, we have generated AtT20 corticotroph cell lines expressing the sense or antisense ICER transcript under the control of the cadmium-inducible human methallothionein IIA promoter. Here we demonstrate that changes in the regulated levels of ICER have drastic consequences on the physiology of the corticotrophs. Ectopic ICER expression induces remarkable modifications in AtT20 morphology. Cells with persistent, nonregulated high levels of ICER are blocked in the G2/M phase of the cell cycle, while the opposite effect is obtained in cells expressing an antisense ICER transcript. We show that the effect of ICER on the AtT20 cell cycle is correlated to a direct down-regulation of the cyclin A gene promoter by ICER. Finally, we show that ACTH hormonal secretion from the corticotrophs is completely blocked by ICER ectopic expression. Interestingly, this effect is not due to a direct regulation of the POMC gene, but is mediated by a transcriptional control of the prohormone convertase 1 gene. These results point to a key regulatory function of CREM in pituitary physiology.

Original languageEnglish
Pages (from-to)1425-1434
Number of pages10
JournalMolecular Endocrinology
Volume11
Issue number10
DOIs
StatePublished - 1 Jan 1997

Fingerprint

Corticotrophs
Cell Cycle
Genes
Response Elements
Proprotein Convertase 1
Cyclin A
Neuroendocrine Cells
Pro-Opiomelanocortin
Endocrine Cells
G2 Phase
Cadmium
Cell Division
Adrenocorticotropic Hormone
Protein Isoforms
Down-Regulation
Cell Line

Cite this

Lamas, Monica ; Molina, Carlos ; Foulkes, Nicholas S. ; Jansen, Erik ; Sassone-Corsi, Paolo. / Ectopic ICER expression in pituitary corticotroph AtT20 cells : Effects on morphology, cell cycle, and hormonal production. In: Molecular Endocrinology. 1997 ; Vol. 11, No. 10. pp. 1425-1434.
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Ectopic ICER expression in pituitary corticotroph AtT20 cells : Effects on morphology, cell cycle, and hormonal production. / Lamas, Monica; Molina, Carlos; Foulkes, Nicholas S.; Jansen, Erik; Sassone-Corsi, Paolo.

In: Molecular Endocrinology, Vol. 11, No. 10, 01.01.1997, p. 1425-1434.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Ectopic ICER expression in pituitary corticotroph AtT20 cells

T2 - Effects on morphology, cell cycle, and hormonal production

AU - Lamas, Monica

AU - Molina, Carlos

AU - Foulkes, Nicholas S.

AU - Jansen, Erik

AU - Sassone-Corsi, Paolo

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