Biomedical subjects

Gemma Janer

Publications and source records attributed to Gemma Janer.

12 recordsLinked to original sources

PubMed2007

Sex steroids and potential mechanisms of non-genomic endocrine disruption in invertebrates.

The review reports on the presence and metabolism of sex steroids in several invertebrate species and provides detailed information on possible mechanisms of endocrine disruption other than the interaction with nuclear receptors. The presence of most vertebrate sex steroids in invertebrate tissues has been demonstrated by liquid or gas chromatography coupled to mass spectrometry. In addition, enzymatic pathways involved in the steroidogenic pathway have been described in at least some invertebrate phyla. Some endocrine disruptors induce alterations in these metabolic pathways and might lead to changes in steroid levels. Growing evidence suggests that estradiol can act through non-genomic pathways in molluscs, and that xenobiotics can as well interfere in these signalling cascades. In spite of these recent advances, most question marks on the action and function of sex steroids in invertebrates remain to be answered.

Animals↗

PubMed2006

Sexual dimorphism in esterified steroid levels in the gastropod Marisa cornuarietis: the effect of xenoandrogenic compounds.

Molluscs can conjugate a variety of steroids to form fatty acid esters. In this work, the freshwater ramshorn snail Marisa cornuarietis was used to investigate sex differences in endogenous levels of esterified steroids. Testosterone and estradiol were mainly found in the esterified form in the digestive gland/gonad complex of M. cornuarietis, and males had higher levels of esterified steroids than females (4-10-fold). Additionally, the ability of several xenobiotics, namely tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN) to interfere with the esterification of testosterone and estradiol was investigated. All three compounds induced imposex - appearance of male sexual characteristics in females. Exposure to TBT led to a decrease in both esterified testosterone (60-85%) and estradiol (16-53%) in females after 100 days exposure, but had no effect on males. Exposure to FEN and MT did not alter levels of esterified steroids in males or in females, although exposed females developed imposex after 150 days exposure. The decrease in esterified steroids by TBT could not be directly linked with a decrease in microsomal acyl-CoA:testosterone acyltransferase (ATAT) activity, which catalyzes the esterification of steroids. In fact, ATAT activity was marginally induced in organisms exposed to TBT for 50 days (1.3-fold), and significantly induced in males and females exposed to MT for 50 days (1.8- and 1.5-fold, respectively), whereas no effect on ATAT activity was observed after 150 days exposure.

Androgens↗

PubMed2006

Steroid levels and steroid metabolism in the mussel Mytilus edulis: the modulating effect of dispersed crude oil and alkylphenols.

Significant amounts of oil and alkylphenols are released into the sea by petroleum installations as a result of discharges of produced water. Some of these pollutants elicit estrogenic responses in fish, but their effects on the endocrine system of molluscs are largely unknown. In this study, mussels Mytilus edulis were exposed to North Sea oil (O) and the mixture of North Sea oil+alkylphenols (OAP), and the effects on tissue steroid levels and steroid metabolism (P450-aromatase and estradiol-sulfotransferase) were monitored. Levels of free testosterone and free estradiol were much higher in gonad tissue than in peripheral tissue, whereas esterified steroids (released after saponification) were of the same order of magnitude in both tissues. Levels of free steroids determined in gonads were not affected by exposure, but esterified steroids significantly increased in OAP exposed mussels (up to 2.4-fold). The sulfation of estradiol was investigated as a conjugation pathway, and increased activities were observed in digestive gland cytosol of both O and OAP exposure groups (up to 2.8-fold). Additionally, increased P450-aromatase activity was determined in OAP exposed mussels (up to three-fold, both in gonad and digestive gland), but not in the O group. Altogether, the results indicate that North Sea oil leads to increased sulfation of estradiol, and that in combination with alkylphenols, additional alterations are observed: increased P450-aromatase, and increased levels of esterified-steroids in gonads. Nonetheless, mussels are able to maintain gonad concentrations of free steroids unaltered, possibly via homeostatic mechanisms such as the conjugation with fatty acid or the formation of sulphate conjugates.

Analysis of Variance↗

PubMed2006

COMPRENDO: Focus and approach.

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose-response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters--Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates) .

Androgens↗

PubMed2005

Effects of 17beta-estradiol exposure in the mussel Mytilus galloprovincialis: a possible regulating role for steroid acyltransferases.

Mussels (Mytilus galloaprovincialis) were exposed to different concentrations of estradiol (20, 200, and 2000 ng/L) in a semi-static regime (1-day dosing intervals) for up to 7 days in an attempt to see how mussels deal with exogenous estrogenic compounds. Whole tissue free-estradiol levels were only significantly elevated at the high exposure dose, whereas total-estradiol (free+esterified) sharply increased in a dose-dependent manner, from 2 ng/g in controls to 258 ng/g at the high exposure group. Neither free nor esterified testosterone levels showed significant differences between control and exposed organisms. The results suggest the existence of mechanisms that allow mussels to maintain their hormonal levels stable, with the exception of the high exposure dose, and the important role that fatty acid esterification, e.g. palmitoyl-CoA:estradiol acyltransferases, may play within those mechanisms. Additionally, the activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase, P450-aromatase, and estradiol-sulfotransferases were investigated in digestive gland microsomal and cytosolic fractions. All these activities were differently affected by estradiol exposure. Overall, the study contributes to the better knowledge of molluscan endocrinology, and defines new mechanisms of regulation of free steroid-levels in mussels.

Acyltransferases↗

PubMed2004

Esterification of vertebrate-type steroids in the Eastern oyster (Crassostrea virginica).

Characteristics of acyl-coenzyme A (acyl-CoA):steroid acyltransferase from the digestive gland of the oyster Crassostrea virginica were determined by using estradiol (E2) and dehydroepiandrosterone (DHEA) as substrates. The apparent Km and Vmax values for esterification of E2 with the six fatty acid acyl-CoAs tested (C20:4, C18:2, C18:1, C16:1, C18:0, and C16:0) were in the range of 9-17 microM E2 and 35-74 pmol/min/mg protein, respectively. Kinetic parameters for esterification of DHEA (Km: 45-120 microM; Vmax: 30-182 pmol/min/mg protein) showed a lower affinity of the enzyme for this steroid. Formation of endogenous fatty acid esters of steroids by microsomes of digestive gland and gonads incubated in the presence of ATP and CoA was assessed, and at least seven E2 fatty acid esters and five DHEA fatty acid esters were observed. Some peaks eluted at the same retention times as palmitoleoyl-, linoleoyl-, oleoyl/palmitoyl-, and stearoyl-E2; and palmitoleoyl-, oleoyl/palmitoyl-, and stearoyl-DHEA. The same endogenous esters, although in different proportions, were produced by gonadal microsomes. The kinetic parameters for both E2 (Km: 10 microM; Vmax: 38 pmol/min/mg protein) and DHEA (Km: 61 microM; Vmax: 60 pmol/min/mg protein) were similar to those obtained in the digestive gland. Kinetic parameters obtained are similar to those observed in mammals; thus, fatty acid esterification of sex steroids appears to be a well-conserved conjugation pathway during evolution.

Acyltransferases↗

PubMed2004

Interaction of tributyltin with hepatic cytochrome P450 and uridine diphosphate-glucuronosyl transferase systems of fish: in vitro studies.

Hepatic microsomes of red mullet (Mullus barbatus) and flounder (Platichthys flesus) were preincubated in the presence of a concentration range of the antifouling agent tributyltin (TBT) chloride, and the interactions of TBT with cytochrome P450 and uridine diphosphate-glucuronyl transferase systems were investigated. The enzyme systems were examined in terms of cytochrome P4501A (CYP1A)-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity and benzo[a]pyrene (BaP) metabolism and in terms of glucuronidation of testosterone and 17beta-estradiol, respectively. Ethoxyresorufin O-deethylase and BaP hydroxylase (BPH) activities of both fish species were progressively inhibited by increasing concentrations of TBT, and the effects were more pronounced for EROD than for BPH (maximal inhibition at 100 microM TBT for EROD and 250-500 microM TBT for BPH). Hydroxylated metabolites of BaP (3-hydroxy-, 7,8-dihydrodiol, and 9,10-dihydrodiol), representing 95% of the total metabolites formed, were reduced up to 75% in the presence of 100 to 500 microM TBT, whereas the formation of other metabolites was less affected. This may alter BaP toxicity and carcinogenicity. Overall, the results were consistent with a specific inhibitory effect of TBT on CYP1A in the two fish species. Additionally, the conjugation of testosterone was significantly inhibited (20%) at low TBT doses (5 microM), with no effect on the glucuronidation of estradiol.

Animals↗

PubMed2003

Social context for workplace health promotion: feasibility considerations in Costa Rica, Finland, Germany, Spain and Sweden.

We constructed a simple, flexible procedure that facilitates the pre-assessment of feasibility of workplace health promotion (WHP) programmes. It evaluates cancer hazards, workers' need for hazard reduction, acceptability of WHP, and social context. It was tested and applied in 16 workplace communities and among 1085 employees in industry, construction, transport, services, teaching and municipal works in Costa Rica, Finland, Germany, Spain and Sweden. Social context is inseparable from WHP. It covers workers' organizations and representatives, management, safety committees, occupational health services, health and safety enforcement agencies, general health services, non-government organizations, insurance systems, academic and other institutions, regulatory stipulations pertaining WHP, and material resources. Priorities, risk definitions, attitudes, hazard profiles, motivations and assessment methods were highly contextual. Management preferred passive interventions, helping cover expert costs, participating in planning and granting time. Trade unions, workers' representatives, safety committees and occupational health services appeared to be important operational partners. Occupational health services may however be loaded with curative and screening functions or be non-existent. We advocate participatory, multifaceted WHP based on the needs and empowerment of the workers themselves, integrating occupational and lifestyle hazards. Workforce in irregular and shift work, in agriculture, in small enterprises, in the informal sector, and immigrant, seasonal and temporary workers represent groups in need of particular strategies such as community health promotion. In a more general framework, social context itself may become a target for intervention.

Attitude to Health↗

PubMed2002

Assessment of feasibility of workplace health promotion.

BACKGROUND: A simple empirically based method for assessment of the feasibility of workplace health promotion programs is described, focusing on cancer hazards (lifestyles, workplace hazards, deficient early detection). The basic components of feasibility are addressed: extent of hazards; needs of employees for hazard reduction and acceptability of WHP; and social context. METHODS: The procedure consists of six modules: guidelines on feasibility assessment; employee questionnaire; interview checklists for probing attitudes of management and partners (social context); data form; debriefing; and assessment of feasibility. Pretesting was completed in 16 workplace communities representing industry, construction, transport, telecommunications, health care, lodging and catering, teaching, and municipality jobs in five countries; a total of 1,085 subjects completed the employee questionnaire on health hazards, needs, and acceptability. RESULTS: The method demonstrated its utility in obtaining and summarizing the necessary data. Feasibility was assessed for the 16 test communities. CONCLUSION: The procedure can be customized; it has a high degree of face validity or understandability, and it is applicable in a wide variety of settings.

Attitude to Health↗

PubMed2002

Health promotion trials at worksites and risk factors for cancer.

Studies of worksite health promotion have frequently reported larger effects than those at the community level. Many of these studies have serious methodological problems. Forty-five worksite health promotion trials following specific quality criteria were selected and estimated for behavioral changes in cancer risk factors and the effectiveness of different intervention components. Tobacco control programs found quit rates of about 5% with relapse rates of 40% to 80% at 6 months after the intervention. Effectiveness increased with the duration of the intervention for at least 6 months, repeated contacts with the participants, continuous support, and tailored messages. There was less evidence for the long-term effectiveness of incentives. Trials on diet, alcohol, physical activity, overweight, and solar radiation showed the same positive trends. The overall evidence indicates a modest but positive effect of health promotion trials at worksites and the effect, for smoking cessation trials, is slightly larger than that of community-based trials. Many of the recommendations made to increase participation and effectiveness were not based on empirical data.

Attitude to Health↗

PubMedDate not supplied

Effects of 17beta-estradiol exposure in the mussel Mytilus galloprovincialis.

Mussels Mytilus galloprovincialis were exposed to different concentrations of estradiol (20, 200, and 2000 ng/l) in a semi-static regime (1-day dosing intervals) for up to 7 days in an attempt to see how mussels dealt with exogenous estrogenic compounds. Sex hormone levels were determined in whole tissue. Free-estradiol was only significantly elevated at the highest exposure dose (up to 10-fold). Most of the estradiol was in the tissues as fatty acid esters (> 78%), which sharply increased in a dose-dependent manner (from 4 ng/g in controls to 258 ng/g at the high exposure group). In contrast, neither free nor esterified testosterone levels showed significant differences between control and exposure groups. The results suggest the existence of mechanisms that allow mussels to maintain their hormonal status, and the important role that fatty acid esterification may play within those mechanisms. Synthesis and conjugation rates of estradiol were further investigated by measuring the activity of P450 aromatase, and palmitoyl-CoA:estradiol acyltransferase, in digestive gland microsomal fractions. Overall, the study contributes to the better knowledge of molluscan endocrinology, and defines new mechanisms of regulation of free steroid-levels in mussels.

Acyl Coenzyme A↗

PubMedDate not supplied

Esterification of vertebrate-like steroids in the eastern oyster (Crassostrea virginica).

The esterification of two model vertebrate steroid hormones - estradiol (E2) and dehidroepiandrosterone (DHEA) - was studied in the oyster Crassostrea virginica. The activity of acyl-CoA:steroid acyltransferase was characterized in microsomal fractions isolated from oyster digestive glands. The apparent Km and Vmax values changed with the fatty acid acyl-CoA used (C20:4, C18:2, C18:1, C16:1, C18:0 or C16:0), and were in the range of 9-17 microM, and 35-74 pmol/min/mg protein for E2, and in the range of 45-120 microM, and 30-182 pmol/min/mg protein for DHEA. Kinetic parameters were also assessed in gonadal tissue. The enzyme saturated at similar concentrations, although conjugation rates were lower than in digestive gland. Preliminary data shows that tributyltin (TBT) in the low microM range (1-50) strongly inhibits E2 and DHEA esterification, the esterification of E2 being more sensitive to inhibition than that of DHEA. Overall, results indicate that apolar conjugation occurs in oysters, in both digestive gland and gonads, at a very similar rate to mammals, suggesting that this is a well conserved conjugation pathway during evolution. Esterification, together with other mechanisms, can modulate endogenous steroid levels in C. virginica, and might be a target for endocrine disrupters, such as TBT.

Animals↗