NIH Research Festival
The hypothalamic GnRH together with gonadal steroids regulates its receptor gene (Gnrhr) transcription in vivo, which leads to crucial changes in GnRHR numbers at the plasma membrane and accompanied alterations in the gonadotroph sensitivity and responsiveness during physiologically relevant situations. Here we investigated in vitro Gnrhr expression in rodent pituitary cells and cell lines. In pituitary cells cultured in the absence of GnRH and steroid hormones, Gnrhr expression was progressively reduced but not abolished. Gnrhr transcription was also operative in LT2 immortalized gonadotrophs never exposed to GnRH. In both cell types, such basal transcription was dependent on intrinsic activity of protein kinase C and was sufficient for the expression of functional GnRHRs. Continuous application of GnRH transiently elevated Gnrhr expression in cultured pituitary cells through calcium and protein kinase C pathways by downstream ERK signaling, followed by a sustained fall without affecting basal expression. GnRH-regulated Gnrhr expression was not operative in embryonic pituitary and LT2 cells, was established neonatally, the sex-specific pattern of response was formed during the peripubertal age, and there was a strong correlation between basal and regulated gene expression during development. These results indicate that Gnrhr transcription is a developing variable that could contribute to initial blockade and subsequent activation of the reproductive system.
Scientific Focus Area: Neuroscience
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