Progesterone and estradiol inhibit cftr-mediated ion transport by
pancreatic epithelial cells.
Sweezey, Neil B., Claude Gauthier, St[acute]ephane Gagnon, Emanuela
Ferretti, and Hinda Kopelman.
Divisions of Gastroenterology/Nutrition and Respiratory Medicine,
Department of Pediatrics, McGill University-Montreal Children's
Hospital, Research Institute, Montreal, Canada
APStracts 3:0092G, 1996.
The cystic fibrosis (CF) gene product, CF transmembrane conductance
regulator (CFTR), is responsible for cAMP-activated chloride (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 the activation by
cAMP, but not by calcium ionophore, of PANC 1 cell volume reduction
under isotonic conditions. The 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 (PCR) 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.
Received 3 January 1996; accepted in final form 17 April 1996.
APS Manuscript Number G6-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96