Expression of candidate Pro-GnRH processing enzymes in rat hypothalamus and an immortalized hypothalamic neuronal cell line

W. C. Wetsel, Z. Liposits, N. G. Seidah, S. Collins

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Since gonadotropin-releasing hormone (GnRH, also referred to as LHRH) is a major hormone regulating mammalian reproduction, identification of the processing steps involved in the conversion of the pro-LHRH to LHRH is fundamental to our understanding of its physiology. Extracts from immortalized LHRH neurons (GT1) were used to isolate the pro-LHRH intermediate products and to identify the enzymes which may participate in these conversions. The GT1 cells contain and secrete a pro-LHRH species that elutes at approximately 10,000-12,000 molecular weight. The pro-LHRH is metabolized to various N- and C-terminally modified LHRH products and to gonadotropin-releasing hormone-associated peptide (GAP). Analyses of these intermediates suggests that, at least, four different enzymatic steps are involved in pro-LHRH processing. Northern blot analyses reveal that prohormone convertase 2 (PC2), carboxypeptidase E, glutaminyl cyclase, and peptidyl-glycine a-amidating monooxygenase are expressed in the GT1 cells and rat hypothalamus. PC2 immunoreactivity is localized to the perikarya and beaded axon-like processes of these cells. SDS-PAGE analyses indicate that PC2 is biosynthesized, processed and secreted by the immortalized LHRH neurons. Our results indicate that the GT1 cell line may serve as a useful model to study the regulation of pro-LHRH processing and that it may also represent an important tool for dissecting the molecular and cellular basis of mammalian reproduction.

Original languageEnglish
Pages (from-to)166-177
Number of pages12
JournalNeuroendocrinology
Volume62
Issue number2
DOIs
Publication statusPublished - Jan 1 1995

Keywords

  • GT1 cells
  • Gonadotropin-releasing hormone, processing

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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