Administration of leuprolide acetate, a GnRH agonist, improves urodynamic parameters in ovariectomized rats

Neurourol Urodyn. 2018 Jun;37(5):1574-1582. doi: 10.1002/nau.23505.

Abstract

Aim: To evaluate the effects of a treatment with leuprolide acetate (LA) on bladder overactivity as well as the expression of gonadotropin releasing hormone receptor (GnRH-R), and neurofilaments NF68 and NF200 in female rats with overactive bladder induced by castration.

Methods: Changes in the urodynamic parameters were determined in SHAM, ovariectomized (OVX) and ovariectomized rats treated with LA (OVX-LA). A semi-quantitative analysis for the expression pattern of GnRH-R and neurofilaments NF68 and NF200 were determined.

Results: Forty-three days after ovariectomy, rats from the OVX group have significant lower values for intercontractile interval (ICI) and compliance (C); as well as higher values for basal bladder pressure (BP) and frequency of non-voiding contractions (NVC). The systemic application of LA increased voiding volume (Vv) and pressure threshold (ThP) in the OVX-LA animals. The application of LA reduced the high frequency of NVC in the OVX rats. No significant differences were found for Vv and NVCs between the OVX-LA vs SHAM groups. At the mid part of the bladder, the presence of GnRH-R was evidenced in the urothelium of the SHAM group. The OVX animals showed different pattern of immunolabeling for GnRH-R as well as for neurofilaments NF200 and NF68, whereas in the OVX-LA group the immunofluorescence pattern was similar to the one seen in SHAM bladders (P < 0.05 for OVX vs OVX + LA).

Conclusions: the results suggest that systemic application of LA can improve bladder dysfunction in castrated rats, and perhaps considered as a treatment for overactive bladder conditions secondary to menopause.

Keywords: GnRH receptor; cystometry; menopause; neuroregeneration; overactive bladder.

MeSH terms

  • Animals
  • Compliance / drug effects
  • Female
  • Leuprolide / pharmacology*
  • Muscle Contraction / drug effects
  • Neurofilament Proteins / biosynthesis
  • Neurofilament Proteins / genetics
  • Ovariectomy*
  • Rats
  • Rats, Wistar
  • Receptors, LHRH / agonists*
  • Receptors, LHRH / biosynthesis
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism
  • Urodynamics / drug effects*
  • Urothelium / drug effects
  • Urothelium / metabolism

Substances

  • Neurofilament Proteins
  • Receptors, LHRH
  • neurofilament protein NF 68
  • neurofilament protein H
  • Leuprolide