AJP - Gastrointestinal and Liver Physiology, Vol 271, Issue 5 747-G754, Copyright © 1996 by American Physiological Society

ARTICLES

Progesterone and estradiol inhibit CFTR-mediated ion transport by pancreatic epithelial cells

N. B. Sweezey, C. Gauthier, S. Gagnon, E. Ferretti and H. Kopelman
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Canada.

The cystic fibrosis (CF), gene product, CF transmembrane conductance regulator (CFTR), is responsible for adenosine 3',5'-cyclic monophosphate (cAMP)-activated Cl- transport in epithelial cells, and mutant CFTR accounts for the pathology in the CF pancreas. We have previously shown that both isolated rabbit pancreatic acini and the human pancreatic duct cell line PANC-1 possess a cAMP-activated Cl- conductance identified as CFTR. We report here that preincubation in either of the female hormones progesterone or beta-estradiol inhibits activation by cAMP, but not by Ca2+ ionophore, of PANC-1 cell volume reduction under isotonic conditions. cAMP-activated cell volume reduction is sensitive to antisense, but not sense, CFTR oligodeoxynucleotide. Furthermore, progesterone inhibits cAMP-activated Cl- efflux from rabbit acinar cells. Moreover preincubation with progesterone, but not beta-estradiol, reduces CFTR mRNA and protein levels as measured using polymerase chain reaction amplification of reverse-transcribed acinar RNA and Western blots of protein from acinar membranes. We conclude that female hormones inhibit CFTR functional activity in pancreatic epithelial cells by different mechanisms.

This article has been cited by other articles:

				J. R. Shaw, K. Gabor, E. Hand, A. Lankowski, L. Durant, R. Thibodeau, C. R. Stanton, R. Barnaby, B. Coutermarsh, K. H. Karlson, et al. Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R1052 - R1060. [Abstract] [Full Text] [PDF]

				Y. Ito, S. Sato, M. Son, M. Kondo, H. Kume, K. Takagi, and K. Yamaki Bisphenol A Inhibits Cl- Secretion by Inhibition of Basolateral K+ Conductance in Human Airway Epithelial Cells J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 80 - 87. [Abstract] [Full Text] [PDF]

				K. Klingel, S. Warntges, J. Bock, C. A. Wagner, M. Sauter, S. Waldegger, R. Kandolf, and F. Lang Expression of cell volume-regulated kinase h-sgk in pancreatic tissue Am J Physiol Gastrointest Liver Physiol, November 1, 2000; 279(5): G998 - G1002. [Abstract] [Full Text] [PDF]

				N. Sweezey, S. Tchepichev, S. Gagnon, K. Fertuck, and H. O'Brodovich Female gender hormones regulate mRNA levels and function of the rat lung epithelial Na channel Am J Physiol Cell Physiol, February 1, 1998; 274(2): C379 - C386. [Abstract] [Full Text] [PDF]

				F. LANG, G. L. BUSCH, M. RITTER, H. VOLKL, S. WALDEGGER, E. GULBINS, and D. HAUSSINGER Functional Significance of Cell Volume Regulatory Mechanisms Physiol Rev, January 1, 1998; 78(1): 247 - 306. [Abstract] [Full Text] [PDF]