title: Estrogen receptor signaling is an unstable feature of the gonadotropic LbetaT2 cell line.
abstract: The murine, gonadotropic LbetaT2 cell line was assessed as a potential in vitro model to analyze estrogen receptor (ER)-mediated regulation of luteinizing hormone (LH) synthesis and secretion. In agreement with limited literature data, repeated exposure to (sub) physiological concentrations of gonadotropin-releasing hormone enhanced LHbeta-subunit gene expression, being the rate-limiting step of LH synthesis, and the corresponding LH secretory response. However, in the same subclone of the LbetaT2 cell line, we observed that LH production was not affected following exposure to E(2), which is in contrast to previously reported weak or modest effects. One explanation may be the absence of measurable ERalpha protein expression on the one hand and impaired ER signal transduction on the other. Furthermore, an alternative ERalpha mRNA splicing variant was detected in the LbetaT2 cell line, which (theoretically) encodes for a protein that may alter ERalpha transcriptional activity, depending on the cellular context. The studied LbetaT2 subclone did not show a generalized impairment of nuclear receptor function, as we observed androgen- and glucocorticoid-induced gene transcription, together with enhanced LH secretory response following dexamethasone treatment. Since its development, the gonadotropic LbetaT2 cell line served as a reference model to study gonadotroph-specific effects because of its mature properties. Nevertheless, this cell line does not seem to be a suitable in vitro model for the study of estrogenic regulatory effects at the level of the pituitary gonadotrophs in view of the unstable nature of ER signaling in LbetaT2 cells.
authors.affiliation: Department of Endocrinology, 6K12IE, Ghent University Hospital, De Pintelaan, 185, B-9000 Ghent, Belgium. frank.eertmans@ugent.be
authors.forename: Frank
authors.initials: F
authors.lastname: Eertmans
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.forename: De Wever
authors.initials: de W
authors.lastname: Olivier
authors.forename: Willem
authors.initials: W
authors.lastname: Dhooge
authors.forename: Dhooge
authors.initials: D
authors.lastname: Willem
authors.forename: Wim
authors.initials: W
authors.lastname: Vanden Berghe
authors.forename: Vanden Berghe
authors.initials: VB
authors.lastname: Wim
authors.forename: Veerle
authors.initials: V
authors.lastname: Bogaert
authors.forename: Bogaert
authors.initials: B
authors.lastname: Veerle
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.forename: Bracke
authors.initials: B
authors.lastname: Marc
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.forename: Haegeman
authors.initials: H
authors.lastname: Guy
authors.forename: Frank
authors.initials: F
authors.lastname: Comhaire
authors.forename: Comhaire
authors.initials: C
authors.lastname: Frank
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.forename: Kaufman
authors.initials: K
authors.lastname: Jean-Marc
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D052681:Gonadotrophs / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D037101:Luteinizing Hormone, beta Subunit; D021122:Protein Subunits; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D003907:Dexamethasone