Amiloride-insensitive nasal potential difference varies with the menstrual cycle in cystic fibrosis.
BACKGROUND
There is no adequate explanation for gender-based differences in rates of mortality and of deterioration in pulmonary function in cystic fibrosis (CF) patients. One potential explanation is that gender hormones (sex steroids) may modulate the severity of CF lung disease, the principal cause of mortality in CF, by altering respiratory transepithelial ion transport.


OBJECTIVE
To determine whether respiratory epithelial ion transport varied during the menstrual cycle of CF females.


METHODS
The nasal transepithelial electrical potential difference (NPD) was determined as a measure of ion transport across human respiratory epithelium, coincident with measurements of endogenous serum hormone levels in the luteal and follicular phases of the menstrual cycle in CF females aged 16-22 years.


RESULTS
The component of the NPD that is insensitive to the Na(+) transport blocker amiloride, but not the amiloride-sensitive component, changed in association with endogenous, menstrual cycle-induced changes in serum levels of progesterone and estrogen (P=0.02, n=7, paired t-test). Measurements using Cl(-) free perfusates suggested that the changes are not a result of Cl(-) conductance.


CONCLUSIONS
Our results suggest that in CF respiratory epithelium amiloride-insensitive, but not amiloride-sensitive, ion transport is altered by female gender hormones in vivo. We speculate that amiloride-insensitive ion transport may contribute to the regulation of human airway surface fluid.
Sweezey
Neil B
NB
Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. neil.sweezey@utoronto.ca
Smith
David
D
Corey
Mary
M
Ellis
Lynda
L
Carpenter
Susan
S
Tullis
D Elizabeth
DE
Durie
Peter
P
O'Brodovich
Hugh M
HM
D000293:Adolescent; D000328:Adult; D000584:Amiloride / Q000494:pharmacology*; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000503:physiopathology*; D004967:Estrogens / Q000097:blood; D005260:Female; D005498:Follicular Phase / Q000097:blood; D006801:Humans; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008183:Luteal Phase / Q000097:blood; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008597:Menstrual Cycle / Q000097:blood / Q000502:physiology*; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D012737:Sex Factors; D026941:Sodium Channel Blockers / Q000494:pharmacology*
D004967:Estrogens; D026941:Sodium Channel Blockers; D011374:Progesterone; D000584:Amiloride