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 (0.01e10 mg DRO/g) for up to
31 days. DRO was detected in the blood (4e27 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), 17a-hydroxyprogesterone (17P4), 17a-hydroxypregnenolone (17P5), androstenedione
(AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a and
cyp11b 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.
Drospirenone (DRO) is one of the most widely used progestins in contraceptive treatments and hormonereplacement therapies. The pharmacokinetics and potential toxicological effects of DRO were investigatedin juvenile sea bass (Dicentrarchus labrax) exposed through the diet (0.01e10 mg DRO/g) for up to31 days. DRO was detected in the blood (4e27 ng/mL) of fish exposed to the highest concentration, withno 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), 17a-hydroxyprogesterone (17P4), 17a-hydroxypregnenolone (17P5), androstenedione(AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a andcyp11b analysed by qRT-PCR in gonads. The significant increase in plasmatic levels of 17P5, 17P4 and ADdetected after 31 days exposure to 10 ng DRO/g together with the increased expression of cyp17a1 infemales 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 beinvestigated.
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