Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are uncertainties regarding the role of sex steroids in sexual development and reproduction of gastropods, leading to the recent doubts as to whether organotin compounds do inhibit steroidogenic enzymes in these species. These doubts have led us to suspect that organotin compounds may affect other target molecules, particularly signal transduction molecules or secondary mediators of steroid hormone and lipid synthesis/metabolism. Therefore, we have studied the effects of TBT exposure through food on acute steroidogenesis, PPARs and CYP3A responses in the presence and absence of a cyclic AMP (cAMP) activator, forskolin. Two experiments were performed. Firstly, juvenile salmon were force-fed once with diet containing TBT doses (0.1, 1 and 10mg/kg fish) dissolved in ethanol and sampled after 72h. Secondly, fish exposed to solvent control and 10mg/kg TBT for 72h were transferred to new tanks and exposed to waterborne forskolin (200microg/L) for 2 and 4h. Our data show that juvenile salmon force-fed TBT showed modulations of multiple biological responses in interrenal tissues that include, steroidogenesis (cAMP/PKA activities; StAR and P450scc mRNA, and plasma cortisol), and mRNA for peroxisome proliferator-activated receptor (PPAR) isoforms (alpha, beta, gamma), acyl-CoA oxidase-1 (ACOX1) and CYP3A/PXR (pregnan X receptor). In addition, forskolin produced differential effects on these responses both singly and also in combination with TBT. Overall, combined forskolin and TBT exposure produced higher effects compared with TBT exposure alone, for most of the responses (cortisol, PPARbeta, ACOX1 and CYP3A). Interestingly, forskolin produced PPAR isoform-specific effects when given singly or in combination with TBT. Several TBT mediated toxicity in fish that includes thymus reduction, decrease in numbers of lymphocytes, inhibition of gonad development and masculinization, including the imposex phenomenon have been reported. When these effects are considered with the present findings, it suggests that studies on mechanisms of action or field studies may reveal endocrine, reproductive or other effects of TBT at lower concentrations than those reported to date from subchronic tests of fishes. Since the metabolic fate of organotin compounds may contribute to the toxicity of these chemicals, the present findings may represent some new aspects of TBT toxicity not previously reported.
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PMID:Modulation of acute steroidogenesis, peroxisome proliferator-activated receptors and CYP3A/PXR in salmon interrenal tissues by tributyltin and the second messenger activator, forskolin. 2021 Nov 55

Reproduction is the goal of living organisms, and environmental conditions that influence sexual development are therefore critical to understanding adaptation in natural populations. It is not surprising that so much attention has been devoted to the impacts of the physical and chemical environment on this process (Vandenberg et al.2012). Chemicals of concern include a variety of endocrine disruptors (EDs) including oestrogen and oestrogen mimics that directly lead to malformation of the gonad. On the molecular side, the impact that EDs have on genes directly involved in the feminization or masculinization of the gonad such as Cyp 19A (or aromatase), foxl2,Sox9, Dmrt1 and NrOb1, has received considerable attention due to their direct involvement in the regulation of oestrogen and testosterone. In this issue of Molecular Ecology, Pascoal et al. (2013) examine the impact of a known endocrine disruptor (tributyltin or TBT) on the transcriptome of the dog whelk, Nucella lapillus (Fig. 1),in relation to the formation of imposex individuals (masculinized females). They conclude that TBT mimics the endogenous ligand of the nuclear retinoid X receptor (RXR) and/or peroxisome profilerator-activated receptor (PPAR) disrupting pathways.
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PMID:Contaminants and impoSEX: transcriptomics of contaminant-induced sex change. 2320 77