title: Drospirenone intake alters plasmatic steroid levels and cyp17a1 expression in gonads of juvenile sea bass.
abstract: Drospirenone (DRO) is one of the most widely used progestins in contraceptive treatments and hormone replacement therapies. The pharmacokinetics and potential toxicological effects of DRO were investigated in juvenile sea bass (Dicentrarchus labrax) exposed through the diet (0.01-10 μg DRO/g) for up to 31 days. DRO was detected in the blood (4-27 ng/mL) of fish exposed to the highest concentration, with no significant bioaccumulation over time and no alteration of hepatic metabolizing enzymes, namely, CYP1A and CYP3A-catalysed activities and UDP-glucuronyltransferase (UGT). Pregnenolone (P5), progesterone (P4), 17α-hydroxyprogesterone (17P4), 17α-hydroxypregnenolone (17P5), androstenedione (AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a and cyp11β analysed by qRT-PCR in gonads. The significant increase in plasmatic levels of 17P5, 17P4 and AD detected after 31 days exposure to 10 ng DRO/g together with the increased expression of cyp17a1 in females evidence the ability of DRO to alter steroid synthesis at low intake concentrations (7 ng DRO/day). However, the potential consequences of this steroid shift for female reproduction remain to be investigated.
authors.affiliation: Environmental Chemistry Department, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Blanco
authors.affiliation: Environmental Chemistry Department, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona, Spain; CIMA, University of Algarve, FCT, Campus de Gambelas, 8005-139 Faro, Portugal.
authors.forename: Denise
authors.initials: D
authors.lastname: Fernandes
authors.affiliation: Instituto de Ciencias del Mar, ICM-CSIC, Passeig Maritim 37-49, 08003 Barcelona, Spain; University of Antofagasta, Av. Angamos 601, Antofagasta, Chile.
authors.forename: Paula
authors.initials: P
authors.lastname: Medina
authors.affiliation: Instituto de Ciencias del Mar, ICM-CSIC, Passeig Maritim 37-49, 08003 Barcelona, Spain. Electronic address: blazquez@icm.csic.es.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Blázquez
authors.affiliation: Environmental Chemistry Department, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona, Spain. Electronic address: cinta.porte@cid.csic.es.
authors.forename: Cinta
authors.initials: C
authors.lastname: Porte
mesh_terms: D000736:Androstenes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001492:Bass / Q000378:metabolism*; D003270:Contraceptive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D029941:Fish Proteins / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006066:Gonads / Q000187:drug effects; D000451:Mineralocorticoid Receptor Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D000736:Androstenes; D003270:Contraceptive Agents; D029941:Fish Proteins; D012739:Gonadal Steroid Hormones; D000451:Mineralocorticoid Receptor Antagonists; C035144:drospirenone
keywords: Metabolism; Progestins; Sea bass; Sex steroids; cyp17a1