Poster Presentation The International Congress of Neuroendocrinology 2014

Modulation of GnRH neurons activity in vivo affects Wnt/β-catenin and BMP signaling in the anterior pituitary gland of female rats (#348)

Alina Gajewska 1 , Marlena Zielinska-Gorska 1 , Marta Baran 1 , Grzegorz Kotarba 1
  1. The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Jablonna N.Warsaw, Poland

In gonadotrope cells, Wnt/β-catenin signaling regulates SF-1 transcription factor gene activity. SF-1 response elements are found in the promoter regions of four gonadotrope signature genes: LHβ, FSHβ α-GSU and GnRH-R. β-catenin and Dax-1 act as SF-1 transcriptional coactivator/repressor, respectively, to affect SF-1 mediated transcription of its target genes. Also functional BMP signaling system is now recognized in gonadotropes for its role in the regulation of FSHβ gene transcription. Kisspeptin peptides act as vital upstream regulators integrating central and peripheral signals with GnRH release whereas RFamide-related peptide-3 (RFRP-3) exerts a powerful inhibitory effect on GnRH neuron firing. In consequence, a potential impact of neurohormones on Wnt/β-catenin and BMP functional signaling at the level of respective genes expression cannot be excluded.. Using in vivo model, i.c.v. microinjections of GnRH; RFRP-3, kisspeptin 1-10 and neurokinin B were given to 4 month old ovariectomized rats. Neuropeptides were infused in the presence of or without their specific receptors’ antagonists. qRT-PCR analysis revealed that GnRH increased SF-1 and β-catenin mRNA expression and GnRH activity inhibition blocked these effects. Kisspeptin impact on SF-1 system activity was exerted via stimulation of Dax-1 gene transcription. Central modulation of GnRH network activity also affected BMP signaling system. An increased BMP-15 and BMPR-1A genes transcription were found after GnRH infusions and this effect required functional GnRHR whereas exogenously i.c.v.given neurokinin B up-regulated BMP-15 and down-regulated BMPR-1A mRNA expression in the anterior pituitary gland. Data demonstrated that neurohormone-induced modulation of endogenous GnRH neurons activity may lead to changes in Wnt/β-catenin and BMP signaling systems activity and in consequence affect target genes expression in the anterior pituitary gland. Taking together, an orchestrated activity of transcription factors genes receiving specific central and peripheral regulatory inputs, could be finally responsible for physiologically variable gonadotrope signature genes expression.

Research was in part supported by NCN grant Nr UMO-012/05/D/NZ9/02292.