Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone

被引:34
作者
Sosnowski, R
Mellon, PL
Lawson, MA
机构
[1] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA
关键词
D O I
10.1210/me.14.11.1811
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The neuropeptide GnRH is a central regulator of mammalian reproductive function produced by a dispersed population of hypothalamic neurosecretory neurons. The principal action of GnRH is to regulate release of the gonadotropins, LH and FSH, by the gonadotrope cells of the anterior pituitary. Using a cultured cell model of mouse pituitary gonadotrope cells, alpha T3-1 cells, we present evidence that GnRH stimulation of alpha T3-1 cells results in an increase in cap-dependent mRNA translation. GnRH receptor activation results in increased protein synthesis through a regulator of mRNA translation initiation, eukaryotic translation initiation factor 4E-binding protein, known as 4EBP or PHAS (protein, heat, and acid stable). Although the GnRH receptor is a member of the rhodopsin-like family of G protein-linked receptors, we show that activation of translation proceeds through a signaling pathway previously described for receptor tyrosine kinases. Stimulation of translation by GnRH is protein kinase C and Ras dependent and sensitive to rapamycin. Furthermore, GnRH may also regulate the cell cycle in alpha T3-1 cells. The activation of a signaling pathway that regulates both protein synthesis and cell cycle suggests that GnRH may have a significant role in the maintenance of the pituitary gonadotrope population in addition to directing the release of gonadotropins.
引用
收藏
页码:1811 / 1819
页数:9
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