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- Larsson, Anders, 1977-
(författare)
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Androgen receptors and endocrine disrupting substances
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Throughout the animal kingdom, organisms are dependent on substances such as steroid hormones to help them maintain internal balances. Examples of important tasks that are under regulation of steroid hormones are somatic and gonadal development, sexual performance and behavior (both social and sexual) as well as sex differentiation. Balance in the biology of reproduction is important for all organisms, and is sensitive to alterations and disturbances. If the environment is altered in a manner that lead to higher estrogenic or androgenic levels, the sex ratio of organisms that do not rely on genetic differences in the sex differentiation, will be biased towards more females or males in the population. It has been known for some time that there are pollutants in the environment that affect steroid pathways, such as the estrogenic and thyroid systems, but not much has been known about the androgenic systems. Examples of populations being masculinized have been recorded, and estrogenic compounds have been known to act as antiandrogens, but not until recently the first androgen agonist was identified. We used a combination of in vitro and computational modeling to identify the brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane, as a potent androgen agonist to the human androgen receptor.In addition to this we cloned and characterized the androgen receptor from, a frequently used model organism, zebrafish (Danio rerio) as a receptor primarily activated by 11-ketotestosterone. This is a feature the zebrafish share with several other teleost fishes, such as the three-spined stickleback. Thus fish androgen receptors differ from most mammalian androgen receptors, where dihydrotestosterone is the most potent activator.
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- Mattsson, Anna, et al.
(författare)
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Activation of estrogen receptor alpha disrupts differentiation of the reproductive organs in chicken embryos
- 2011
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 172:2, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Gonadal estrogen plays an important role in the differentiation of a female phenotype in birds. Exogenous compounds that interfere with estrogen signaling, for instance by binding to the estrogen receptors alpha and beta (ER alpha and ER beta), are therefore potential disruptors of sexual differentiation in birds. The ER alpha agonist propyl-pyrazole-triol (PPT), the ER alpha antagonist methyl piperidino pyrazole (MPP) and the ER beta agonist diarylproprionitrile (DPN) were used in the present study to explore the roles of the ERs in normal and disrupted sex differentiation in the chicken embryo. Activation of ER alpha by PPT caused disturbed differentiation of the reproductive organs in both sexes. In male embryos, PPT caused left-side ovotestis formation and retention of the Mullerian ducts. In female embryos, PPT caused retention of the right Mullerian duct (which normally regresses) and malformation of both Mullerian ducts. PPT also induced hepatic expression of mRNA for the estrogen-regulated egg yolk protein apoVLDL II. Notably, none of these effects were observed following treatment with DPN. ER alpha-inactivation by MPP counteracted the action of PPT but had little effect by its own. Our results indicate that ER alpha plays an important role in sex differentiation of the reproductive tract in female chicken embryos and show that ERa can mediate xenoestrogen-induced disturbances of sex differentiation.
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- Mattsson, Anna, et al.
(författare)
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Selective estrogen receptor alpha activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos
- 2008
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Ingår i: Reproduction. - 1470-1626 .- 1476-3990. ; 136:2, s. 175-186
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Tidskriftsartikel (refereegranskat)abstract
- The Japanese quail (Coturnix japonica) is a widely used model species for studying the roles of steroid hormones in avian sex differentiation. The aim of the present study was to elucidate the significance of estrogen receptors alpha and beta (ER alpha and ER beta) in normal sex differentiation of the reproductive organs in the Japanese quail and in xenoestrogen-induced disruption of reproductive organ differentiation. Real-time PCR indicated that ER alpha (ESR1) mRNA is expressed in both right and left gonads and Mullerian ducts (MDs) in both sexes during early morphological differentiation. ER beta (ESR2) transcripts were also detected in gonads and MDs, but at very low levels. Both receptor subtypes were expressed in the liver and may therefore mediate the expression of estrogen-regulated egg-yolk proteins. Aromatase mRNA was expressed at much higher levels in female than male gonads as early as embryonic day 5, indicating early sex differences in estrogen synthesis. Treatment with the ER alpha-selective agonist propyl pyrazole triol showed that frequently reported xenoestrogen effects, such as ovotestis formation, abnormal MD development, and hepatic expression of egg-yolk proteins, were induced by selective activation of ER alpha. Taken together, our results suggest that activation of ER alpha is crucial for estrogen-dependent sex differentiation of the reproductive organs and that ER alpha mediates xenoestrogen-induced toxicity during reproductive development in birds.
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- Strömqvist, Marie, et al.
(författare)
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Transcription of genes involved in fat metabolism in chicken embryos exposed to the peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist GW7647 or to perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA)
- 2012
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Ingår i: Comparative Biochemistry and Physiology - Part C. - : Elsevier. - 1532-0456 .- 1878-1659. ; 156:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl acids (PFAAs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are developmental toxicants in various animal classes, including birds. Both compounds interact with peroxisome proliferator-activated receptors (PPARs), but it is not known whether activation of PPARs is involved in their embryo toxicity in birds. We exposed chicken embryos via egg injection at a late developmental stage to GW7647, a potent PPAR alpha agonist in mammals, and to PFOS or PFOA. Mortality was induced by PFOS and PFOA but not by GW7647. Transcripts of a number of genes activated by PPAR alpha agonists in mammals were analyzed in liver and kidney of 18-day-old embryos. Several of the genes were induced in both liver and kidney following exposure to GW7647. Treatment with PFOA resulted in induction of acylcoenzyme A oxidase mRNA in liver, whereas none of the genes were significantly induced by PFOS treatment. No up-regulation of gene transcription was found in kidney following treatment with PFOS or PFOA. Principal component analysis showed that PFOA caused an mRNA expression pattern in liver more similar to the pattern induced by GW7647 than PFOS did. Our findings do not support that the embryo mortality by PFOS and PFOA in chicken embryos involves PPAR alpha activation.
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