Effect of 5β-dihydrotestosterone on vasodilator function and on cell proliferation

PLoS One. 2024 Oct 23;19(10):e0312080. doi: 10.1371/journal.pone.0312080. eCollection 2024.

Abstract

Aging is one of the main factors associated with cardiovascular diseases. Androgens exert beneficial effects on the cardiovascular system and testosterone (TES) replacement therapy improves cardiometabolic risk factors. However, TES is contraindicated in patients with prostate cancer due to its proliferative effects on prostatic tumor cells. Additionally, TES and its reduced metabolites 5α- and 5β-dihydrotestosterone (5α-DHT and 5β-DHT) exert vasodilatory effects. Since androgen levels decrease during aging and 5β-DHT lacks genomic effects, this study is focused on analyzing its effect on vasodilator function and the proliferation rate of prostatic tumor and vascular smooth muscle cells. To study the vascular function, mesenteric arteries from aged-orchidectomized Sprague-Dawley rats were used. Mesenteric segments were divided into one control (without treatment) and three groups with the androgens (10 nM, 30 min) to analyze: acetylcholine- and sodium nitroprusside-induced responses and nitric oxide and superoxide anion production. To analyze cell proliferation, the effect of androgens on cell viability was determined. The results showed that 5β-DHT improves vasodilator function in arteries from aged-orchidectomized rats and induces antioxidant action, while the proliferation rate of the androgen-dependent prostatic tumor cells remains unaltered. These results make 5β-DHT a promising therapeutic agent for the treatment of cardiovascular pathologies.

MeSH terms

  • Acetylcholine / pharmacology
  • Androgens / pharmacology
  • Animals
  • Cell Proliferation* / drug effects
  • Dihydrotestosterone* / pharmacology
  • Humans
  • Male
  • Mesenteric Arteries / drug effects
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Nitric Oxide / metabolism
  • Nitroprusside / pharmacology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Rats
  • Rats, Sprague-Dawley*
  • Superoxides / metabolism
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Dihydrotestosterone
  • Vasodilator Agents
  • Nitric Oxide
  • Superoxides
  • Nitroprusside
  • Acetylcholine
  • Androgens

Grants and funding

This study was supported by a grant from the Instituto de Salud Carlos III (PI19/01282) and Fondo Europeo de Desarrollo Regional to M. Ferrer, and a grant from the Ministry of Science and Innovation of Spain (PID2020-115371RB-I00) to L.M. Botella. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.