Estrogen receptor signaling is an unstable feature of the gonadotropic LβT2 cell line

The murine, gonadotropic LβT2 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 LHβ-subunit gene expression, being the rate-limiting step of LH synthesis, and the corresponding LH secretory response. However, in the same subclone of the LβT2 cell line, we observed that LH production was not affected following exposure to E2, which is in contrast to previously reported weak or modest effects. One explanation may be the absence of measurable ERα protein expression on the one hand and impaired ER signal transduction on the other. Furthermore, an alternative ERα mRNA splicing variant was detected in the LβT2 cell line, which (theoretically) encodes for a protein that may alter ERα transcriptional activity, depending on the cellular context.The studied LβT2 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 LβT2 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 LβT2 cells.