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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Gonadotropin-inhibitory hormone inhibits gnrh-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 Cells
Endocrinology, Volume 153, No. 5, Year 2012
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Description
A neuropeptide that directly inhibits gonadotropin secretion from the pituitary was discovered in quail and named gonadotropin-inhibitory hormone (GnIH). The presence and functional roles of GnIH orthologs, RF-amide-related peptides (RFRP), that possess a common C-terminal LPXRF-amide (X = LorQ) motif have also been demonstrated in mammals. GnIH orthologs inhibit gonadotropin synthesis and release by acting on pituitary gonadotropes and GnRH neurons in the hypothalamus via its receptor (GnIH receptor). It is becoming increasingly clear that GnIH is an important hypothalamic neuropeptide controlling reproduction, but the detailed signaling pathway mediating the inhibitory effect of GnIH on target cells is still unknown. In the present study, we investigated the pathway of GnIH cell signaling and its possible interaction with GnRH signaling using a mouse gonadotropecell line, LβT2. First, we demonstrated the expression of GnIH receptor mRNA in LβT2 cells by RT-PCR. We then examined the inhibitory effects of mouse GnIH orthologs [mouse RFRP (mRFRP)] on GnRH-induced cell signaling events. We showed that mRFRP effectively inhibited GnRH-induced cAMP signaling by using a cAMP-sensitive reporter system and measuring cAMP levels, indicating that mRFRP function as an inhibitor of adenylate cyclase. We further showed that mRFRP inhibited GnRH-stimulated ERK phosphorylation, and this effect was mediated by the inhibition of the protein kinase A pathway. Finally, we demonstrated that mRFRP inhibited GnRHstimulated gonadotropin subunit gene transcriptions and also LH release. Taken together, the results indicate that mRFRP function as GnIH to inhibit GnRH-induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/protein kinase A-dependent ERK activation in LβT2 cells. © 2012 by The Endocrine Society.
Authors & Co-Authors
Son, You Lee
Japan, Tokyo
Waseda University
Ubuka, Takayoshi
Japan, Tokyo
Waseda University
Millar, Robert P.
South Africa, Cape Town
University of Cape Town
South Africa, Pretoria
University of Pretoria
United Kingdom, Edinburgh
The University of Edinburgh
Kanasaki, Haruhiko
Japan, Matsue
Shimane University
Tsutsui, Kazuyoshi
Japan, Tokyo
Waseda University
Statistics
Citations: 109
Authors: 5
Affiliations: 5
Identifiers
Doi:
10.1210/en.2011-1904
ISSN:
00137227
Research Areas
Genetics And Genomics