Estrogen receptor signaling is an unstable feature of the gonadotropic LbetaT2 cell line.
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.
Eertmans
Frank
F
Department of Endocrinology, 6K12IE, Ghent University Hospital, De Pintelaan, 185, B-9000 Ghent, Belgium. frank.eertmans@ugent.be
De Wever
Olivier
O
Olivier
De Wever
de W
Dhooge
Willem
W
Willem
Dhooge
D
Vanden Berghe
Wim
W
Wim
Vanden Berghe
VB
Bogaert
Veerle
V
Veerle
Bogaert
B
Bracke
Marc
M
Marc
Bracke
B
Haegeman
Guy
G
Guy
Haegeman
H
Comhaire
Frank
F
Frank
Comhaire
C
Kaufman
Jean-Marc
JM
Jean-Marc
Kaufman
K
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
D037101:Luteinizing Hormone, beta Subunit; D021122:Protein Subunits; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D003907:Dexamethasone