Combinatorial effects of genistein and sex-steroids on the level of cystic fibrosis transmembrane regulator (CFTR), adenylate cyclase (AC) and cAMP in the cervix of ovariectomised rats

Reprod Toxicol. 2015 Dec:58:194-202. doi: 10.1016/j.reprotox.2015.10.017. Epub 2015 Oct 31.

Abstract

The combinatorial effects of genistein and estrogen (E) or estrogen plus progesterone (E+P) on CFTR, AC and cAMP levels in cervix were investigated. Ovariectomised adult female rats received 50 or 100mg/kg/day genistein with E or E followed by E+P [E+(E+P)] for seven consecutive days. Cervixes were harvested and analyzed for CFTR mRNA levels by Real-time PCR. Distribution of AC and CFTR proteins in endocervix were observed by immunohistochemistry. Levels of cAMP were measured by enzyme-immunoassay. Molecular docking predicted interaction between genistein and AC. Our results indicate that levels of CFTR, AC and cAMP in cervix of rats receiving genistein plus E were higher than E-only treatment (p<0.05) while genistein plus [E+(E+P)] were higher than E+(E+P)-only treatment (p<0.05). In conclusions, increased levels of CFTR, AC and cAMP in cervix of E and E+(E+P)-treated rats by genistein could affect the cervical secretory function which could influence the female reproductive processes.

Keywords: AC; CFTR; Cervix; Genistein; Sex-steroids; cAMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / chemistry
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Cervix Uteri / drug effects*
  • Cervix Uteri / enzymology
  • Cyclic AMP / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Estrogens / pharmacology*
  • Female
  • Genistein / chemistry
  • Genistein / metabolism
  • Genistein / pharmacology*
  • Genistein / toxicity
  • Molecular Docking Simulation
  • Ovariectomy*
  • Progesterone / pharmacology*
  • Protein Binding
  • Protein Conformation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Time Factors
  • Up-Regulation

Substances

  • CFTR protein, rat
  • Estrogens
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Progesterone
  • Genistein
  • Cyclic AMP
  • Adenylyl Cyclases