Effects of finasteride on steroid production and gene expression in male fathead minnow (Pimephales promelas) and medaka (Oryzias latipes)
Abstract:
The presence of pharmaceuticals in aquatic environments raises concerns due to their specific modes of action on conserved molecular targets. Finasteride (FIN), a human pharmaceutical that inhibits 5α-reductase (5αR) and reduces dihydrotestosterone (DHT) synthesis, is known to suppress masculine traits in mammals. Two aquatic laboratory studies were conducted to investigate whether FIN exerts similar effects in fish by exposing adult male fathead minnows and Japanese medaka – two phylogenetically distinct species with different androgen receptor subtypes – to 1 mg/L of dissolved FIN under flow-through conditions. Time-course samplings were performed at six time points, as fish were sacrificed after 2, 6, 24, 48, 168, and 504 hours. Endpoints included plasma testosterone (T) and DHT concentrations, testes srd5a2 (5αR) gene expression, secondary sex characteristics, and internal plasma FIN concentrations. In fathead minnows, plasma DHT was significantly reduced (p<0.001), and in both species, srd5a2 expression was significantly upregulated (fathead minnow: p<0.001; medaka: p=0.006), suggesting a conserved role of DHT and 5αR in fish and higher vertebrate androgen regulation. Plasma FIN concentrations exceeded surrounding water concentrations after 48 hours. However, high individual variability in plasma FIN concentrations and hormone levels limited direct concentration-response assessments. These findings support read-across approaches for endocrine-active pharmaceuticals and reinforce the relevance of fish models for ecological hazard and risk assessment, potentially reducing vertebrate use in toxicological testing.
Advisor: Professor Kenneth Oliveira
Committee Members:
- Professor Whitney Hable
- Professor Robert Drew
SENG 118
Kenneth Oliveira
508.999.8208
koliveira@umassd.edu