CFTR is functionally active in GnRH-expressing GT1-7 hypothalamic neurons

• Published in: American Journal of Physiology: Cell Physiology 1999-09, Vol.277 (3), p.C563-C571
• Main Authors: Weyler, Richard T, Yurko-Mauro, Karin A, Rubenstein, Ronald, Kollen, Wouter J. W, Reenstra, William, Altschuler, Steven M, Egan, Marie, Mulberg, Andrew E
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.1999.277.3.C563

Divisions of 1  Gastroenterology and Nutrition and 3  Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Departments of 2  Clinical Research and 4  Pediatrics, A. I. duPont Hospital for Children, Thomas Jefferson University, Wilmington, Delaware 19803; and 5  Division of Pulmonary Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 We have demonstrated the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, mRNA, and protein within the rat and human brains, in areas regulating sexual differentiation and function. We have found that GT1-7, a gonadotropin-releasing hormone (GnRH)-secreting hypothalamic neuronal cell line, expresses the CFTR gene, mRNA, and protein and cAMP-dependent 36 Cl efflux. A linear 7-pS Cl conductance, which is stimulated by ATP and cAMP analogs and inhibited by glibenclamide, consistent with CFTR activity, has been identified in GT1-7 cells. Antisense oligo(dN) generated against exon 10 of the CFTR gene transcript (mRNA) inhibit GnRH secretion into media [312 ± 73, 850 ± 150, 963 ± 304, and 912   ± 74 pg GnRH/4 × 10 6 cells for antisense, sense, missense, and no oligo(dN), respectively; P