Premium
Peroxisome proliferator receptor γ agonists alter electrolyte transport across porcine vas deferens epithelia
Author(s) -
Hull Jacob,
Wang Qian,
Wang Florence,
Akoyev Vladimir,
Schultz Bruce D.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1039.13
Subject(s) - endocrinology , forskolin , medicine , epithelial sodium channel , prostaglandin d2 , agonist , amiloride , chemistry , receptor , biology , prostaglandin , sodium , organic chemistry
Elevated levels of 15_deoxy_Δ12_14_prostaglandin_J2 (15dPGJ2) have been reported in the reproductive tracts of some cases of male infertility. The goal for this project was to determine a possible mechanism by which 15dPGJ2, an endogenous PPARγ ligand, might contribute to male infertility. Vas deferens epithelial cells were isolated from pigs, cultured for 14–21 days and exposed to dexamethasone and/or PPARγ agonists for the final 3–4 days of culture. Cells were mounted in modified Ussing chambers and exposed to amiloride (ENaC blocker), forskolin (adenylyl cyclase activator), and DASU□02 (CFTR blocker). Amiloride sensitive current induced by dexamethasone was potentiated two‐fold by concurrent rosiglitazone exposure while there was no effect on baseline, forskolin or DASU‐02 responses. Protein and RNA were isolated. Western blots suggest a decrease in CFTR expression and an increase in α, β, and γ ENaC subunits. RT‐PCR detected a decrease in RNA coding for CFTR. PPARγ agonist treatment in the PVD9902 cell line attenuated forskolin and DASU‐02 responses. These effects were concentration dependent, induced by structurally distinct PPARγ agonists, and blocked by a PPARγ antagonist, T0070907. These outcomes suggest that PPARγ activation by 15dPGJ2 in the reproductive duct could alter luminal electrolytes, which would likely affect sperm viability and function. [NIH R01‐HD058398 & P20‐RR017686 Core C]