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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Biosciences & Biotechnology Laboratory » Research » Publications at this Location » Publication #339759

Title: Ets-1 is a target of MAPK signaling in the embryonic anterior pituitary gland during glucocorticoid initiation of pituitary growth hormone expression

item ELLESTAD, LAURA - University Of Maryland
item Proszkowiec-Weglarz, Monika
item PORTER, TOM - University Of Maryland

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/19/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Glucocorticoids play a critical role in functional differentiation of somatotrophs, the growth hormone (GH)-producing cells within the anterior pituitary gland. In chicken embryonic day 11 (e11) pituitary cells, premature induction of growth hormone (GH) resulting from corticosterone (CORT) treatment is suppressed by an inhibitor of ERK1/2 signaling, and CORT stimulates ERK1/2 pathway activity in these cells. Along with the glucocorticoid receptor (GR), Ets-1 has recently been identified as a transcription factor that may regulate CORT stimulation of GH transcription through a glucocorticoid-responsive region in the chicken GH promoter. The objective of these experiments was to investigate molecular mechanisms by which ERK1/2 signaling, Ets-1, and GR play a role in glucocorticoid initiation of pituitary GH expression during embryonic development. A two-hybrid system assay was conducted in a chicken hepatoma cell line (LMH) to investigate whether GR and Ets-1 interact, and there was no evidence of direct protein-protein interaction between the two under either basal or CORT-treated conditions (n=4). In order to evaluate if ERK1/2 pathway activation leads to phosphorylation of Ets-1, LMH cells were transfected with a constitutively active element of the ERK1/2 pathway (caMEK1) in the absence and presence of Ets-1. Results indicated that Ets-1 can be directly phosphorylated at threonine-38 (pT38) by ERK1/2 pathway activation (P<0.05; n=4). In addition, the level of pT38 in Ets-1 was increased in CORT-treated e11 anterior pituitary cells in a manner reflecting ERK1/2 activation, with an increase at 5, 30, and 90 min and a reduction after longer exposure (P<0.05; n=4). Further, CORT-induced pT38 in Ets-1 in e11 pituitary cells was completely blocked in the presence of an ERK1/2 pathway inhibitor (n=2). We conclude that while direct interaction between GR and Ets-1 does not play a role in CORT stimulation of GH, activation of ERK1/2 signaling by CORT results in phosphorylation of Ets-1 at T38, and this phosphorylation event is necessary for initiation of GH expression during cellular differentiation of pituitary somatotrophs in the chick embryo. Key Words:corticosterone, ERK1/2, adenohypophysis, transcription factor, chicken, development