Neuroendocrinology
Regulation of Gonadotropin-Releasing Hormone
Expression of Candidate Pro-GnRH Processing Enzymes in Rat Hypothalamus and an Immortalized Hypothalamic Neuronal Cell LineWetsel W.C.a · Liposits Z.b · Seidah N.G.c · Collins S.daHormone Action Workgroup, Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., USA; bDepartment of Anatomy, Albert Szent-Györgyi Medical University, Szeged, Hungary; cJ.A. deSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Insitute of Montreal (affiliated with ΓUniversité de Montréal), Que., Canada; dDivision of Biological Psychiatry, Duke University Medical Center, Durham, N.C., USA
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Article / Publication Details
Received: December 12, 1994
Accepted: February 22, 1995
Published online: April 09, 2008
Issue release date: 1995
Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
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 α-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.
© 1995 S. Karger AG, Basel
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Article / Publication Details
Received: December 12, 1994
Accepted: February 22, 1995
Published online: April 09, 2008
Issue release date: 1995
Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
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