Effects of agonists for estrogen receptor α and β on ovariectomy-induced lower urinary tract dysfunction in the rat

Am J Physiol Renal Physiol. 2014 Jan;306(2):F181-7. doi: 10.1152/ajprenal.00298.2013. Epub 2013 Nov 20.


The postmenopausal hypoestrogen status induces various lower urinary tract dysfunctions. Ovariectomized (OVX) rats exhibit voiding abnormalities, including increased postvoiding residual urine (PVR), decreased voiding efficiency (VE), and altered coordination between the detrusor and external urethral sphincter (EUS). Estradiol replacement partially normalizes voiding function in OVX rats. We determined if selective agonists for estrogen receptor (ER)α and/or ERβ can reverse lower urinary tract dysfunction in OVX rats. Cystometry and EUS electromyograms (EMGs) were recorded 6 wk after bilateral OVX in urethane-anesthetized female Sprague-Dawley rats. Animals received daily subcutaneous injections of selective ERα [propylpyrazole triol (PPT)] or ERβ [diarylpropionitrile (DPN)] agonists or vehicle for 1 wk starting on the fifth week after OVX. PPT (1 mg·kg(-1)·day(-1)) decreased PVR, improved VE, and shortened the EUS EMG active period (AP) during voiding. DPN (2 or 5 mg·kg(-1)·day(-1)) did not alter cystometric parameters or EUS EMG activity. Combined PPT + DPN treatment elicited changes in PVR, VE, and AP, similar to those induced by PPT alone, but also increased the EUS EMG silent period and volume threshold for triggering micturition. PPT increased uterine weight fourfold and decreased body weight by 11%. DPN increased uterine weight 30-45% but decreased body weight by 3-5%. Reduced voiding efficiency in OVX rats can be reversed by 1-wk drug treatment that selectively targets ERα and reduces AP during EUS bursting. Combined pharmacological activation of ERα and ERβ further enhanced EUS bursting by increasing the EUS EMG silent period and also facilitated bladder storage mechanisms by increasing the volume threshold.

Keywords: bladder; estrogen receptors; external urethral sphincter; lower urinary tract; ovariectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Electromyography
  • Estrogen Receptor alpha / agonists*
  • Estrogen Receptor beta / agonists*
  • Female
  • Nitriles / pharmacology
  • Organ Size / drug effects
  • Ovariectomy*
  • Phenols
  • Propionates / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiology
  • Urodynamics / drug effects
  • Urologic Diseases / drug therapy*
  • Urologic Diseases / physiopathology


  • 2,3-bis(4-hydroxyphenyl)-propionitrile
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Nitriles
  • Phenols
  • Propionates
  • Pyrazoles
  • 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol