Progesterone Downregulates Oestrogen-Induced Expression of CFTR and SLC26A6 Proteins and mRNA in Rats’ Uteri

Abstract

Under progesterone (P) dominance, fluid loss assists uterine closure which is associated with pH reduction. We hypothesize that P inhibits uterine fluid secretion and HCO3− transport. Aim. to investigate the expression of Cystic Fibrosis Transmembrane Regulator (CFTR) and Cl−/HCO3− exchanger (SLC26A6) under P effect. Method. Uteri from ovariectomized steroid replaced and intact rats at different stages of oestrous cycle were analyzed for changes in protein and mRNA expressions. Results. P inhibits CFTR and SLC26A6 proteins and mRNA expression while oestrogen (E) causes vice versa. E treatment followed by P causes a reduction in these transporters' mRNA and protein. Similar changes occur throughout the oestrous cycle; that is, CFTR mRNA expression was high at proestrus while SLC26A6 mRNA and protein expressions were increased at proestrus and estrus. At diestrus, however, the expression of these transporters' protein and mRNA was reduced. Conclusion. Inhibition of CFTR and SLC26A6 expressions may explain the reduced fluid volume and pH under P-mediated effect.

Estrogen, progesterone, and genistein differentially regulate levels of expression of α-, β-, and γ-epithelial sodium channel (ENaC) and α-sodium potassium pump (Na+/K+-ATPase) in the uteri of sex steroid–deficient rats

“…However, under progesterone influence, markedly enhanced a-, b-, and g-ENaC expression would contribute toward net uterine luminal fluid reabsorption. This would be further assisted by increased expression of a-Na þ /K þ -ATPase (as observed in this study) and downregulation of CFTR expression by progesterone [43]. In addition, progesterone was also reported to upregulate the expression of AQP 1 and 5 channels that could enhance uterine fluid absorption [44].…”

Emerging role of cystic fibrosis transmembrane conductance regulator as an epigenetic regulator: linking environmental cues to microRNAs

“…Studies on both rodents and humans have revealed that the expression of CFTR in the female reproductive tract is enhanced by oestrogens and suppressed by progesterone in vitro or in vivo. 23,[103][104][105][106][107][108][109] In airway cells, b-oestradiol was found to promote CFTR protein maturation by upregulating the CFTR-interacting protein Na + /H + exchanger regulatory factor (NHERF) 1. 110 A recent study using nucleosome mapping across the CFTR locus identified the glucocorticoid receptor as a trans-acting factor regulating CFTR transcription.…”

Testosterone regulates levels of cystic fibrosis transmembrane regulator, adenylate cyclase, and cAMP in the seminal vesicles of orchidectomized rats

“…Cystic Fibrosis transmembrane regulator (CFTR) is a cAMP-dependent Cl -channel which mediates luminal transport of Cl -and HCO 3 - [11]. Defective CFTR gene was observed in autosomal recessive disease of Cystic Fibrosis (CF) [12].…”