Translational control of gene expression in the gonadotrope

Abstract

The study of gene expression in gonadotropes has largely focused on the variety of mechanisms regulating transcription of the gonadotropin genes and ancillary factors that contribute to the overall phenotype and function of these cells in reproduction. However, there are aspects of the response to GNRH signaling that are not readily explained by changes at the level of transcription. As our understanding of regulation at the level of mRNA translation has increased, it has become evident that GNRH receptor signaling engages multiple aspects of translational regulation. This includes activation of cap-dependent translation initiation, translational pausing caused by the unfolded protein response and RNA binding protein interaction. Gonadotropin mRNAs and the mRNAs of other factors that control the transcriptional and signaling responses to GNRH have been identified as targets of regulation at the level of translation. In this review we examine the impact of translational control of the expression of gonadotropin genes and other genes relevant to GNRH-mediated control of gonadotrope function.

Brain‐derived neurotrophic factor is expressed in rat and human placenta and its serum levels are similarly regulated throughout pregnancy in both species

“…Unexpectedly, after 12 days of gestation, serum BDNF levels were increased suggesting that BDNF does not modulate food intake or glucose levels in late pregnancy. The present study demonstrates that the post‐transcriptional regulation is not co‐directional with transcriptional regulation in placenta with respect to BDNF and its receptor, a phenomenon that has been observed in studies of other genes …”

Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells

“…mTORC1 associates with regulatory associated protein of mTOR (Raptor) and mammalian lethal with SEC13 protein 8 (mLST8) and is sensitive to the inhibitor Rapamycin (RAPA). In gonadotropes, mTORC1 has a well-established role in regulating cap-dependent translational through phosphorylation of both 4E-BP1 and the ribosomal protein S6 kinase (Kim, Do and Lawson, 2014; Nguyen, Santos, Kreidel et al, 2004; Sosnowski, Mellon and Lawson, 2000). …”

Time‐of‐day‐dependent sensitivity of the reproductive axis to RFamide‐related peptide‐3 inhibition in female Syrian hamsters

“…It is also possible that post-transcription/translation modifications lead to differential GnRH peptide release. 67 Finally, we cannot exclude the possibility that the removal of endogenous ovarian hormones alters the typical hypothalamic response to RFRP-3 communication.…”

“…These unexpected relationships between the pattern of Gnrh mRNA and daily change in LH are possibly a result of the disparity between the time at which blood and brain samples were collected (ie, blood samples were collected 20 min post‐treatment, whereas brains were collected 2 h post‐treatment). It is also possible that post‐transcription/translation modifications lead to differential GnRH peptide release . Finally, we cannot exclude the possibility that the removal of endogenous ovarian hormones alters the typical hypothalamic response to RFRP‐3 communication.…”