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Environmental Pollutants Alter Estro...

Karim, Silvia.

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Environmental Pollutants Alter Estrogen and Thyroid Hormone Response and Appetite Control in Zebrafish.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Environmental Pollutants Alter Estrogen and Thyroid Hormone Response and Appetite Control in Zebrafish./
作者:	Karim, Silvia.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
面頁冊數:	151 p.
附註:	Source: Dissertations Abstracts International, Volume: 85-02, Section: B.
Contained By:	Dissertations Abstracts International85-02B.
標題:	Bioengineering. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30635462
ISBN:	9798380142434

Environmental Pollutants Alter Estrogen and Thyroid Hormone Response and Appetite Control in Zebrafish.
Karim, Silvia.

Environmental Pollutants Alter Estrogen and Thyroid Hormone Response and Appetite Control in Zebrafish. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 151 p.

Source: Dissertations Abstracts International, Volume: 85-02, Section: B.

Thesis (Ph.D.)--Indiana University, 2023.

Many environmental pollutants are endocrine disruptors; chemicals that interfere with the body's hormones in the endocrine systems. In this thesis, endocrine disruption of estrogen and thyroid hormone signaling were investigated using zebrafish as a model system. A common pollutant is bisphenol A (BPA), an estrogenic endocrine disruptor, which has been suggested to act as an obesity inducing chemical or obesogen. BPA analogues have been synthesized to replace BPA, but they need to be meticulously studied for safety. We used transgenic estrogen reporter Tg (5xERE:GFP) zebrafish to study estrogenic effects of the bisphenols, and found that the BPA analogues BPA, BPAF, BPC, BPE and BPC-Cl have strong estrogenic activities, whereas BPS has a weak estrogenic activity. We further showed that exposure to BPAF and BPC-Cl increase endogenous estrogen 17beta-estradiol (E2) levels in zebrafish larvae, indicating that bisphenol exposures result in a feed-forward response that can further augment the estrogenic activity of these compounds.For thyroid hormone disruption, we evaluated the efficiency of a transgenic thyroid hormone reporter zebrafish to signal perturbations of the hypothalamus-pituitary-thyroid (HPT) axis. We tested 12 different chemicals with known effects on the HPT axis or thyroid hormone (T4) metabolism. We found that the fish correctly responded to exposure to T4 and T3 (the active form of T4) and to the herbicide pronamide and the steroid pregnenolone, which both are known to induce metabolization of T4 via the uridine diphosphate glucuronosyl transferase (UGT) pathways.Over the past few decades, obesity has drastically soared to epidemic levels. To study the obesogenic capacity of BPA and its analogues, the effect of bisphenol exposure on eating behavior and on the gene expression for hormones controlling hunger (ghrelin) and satiety (leptin) were examined. Zebrafish larvae were exposed to the bisphenols, followed by being fed a stained egg yolk powder for an hour. Exposures to BPA, BPAF, BPE, BPC, BPC-Cl and BPS, resulted in increased amounts of food in the gut of the larvae. We further found that leptin mRNA expression was downregulated with the increasing concentrations of BPA, BPAF and BPC-Cl, whereas ghrelin mRNA expression was upregulated by BPC-Cl exposure. Thus, bisphenol exposures resulted in an augmented eating behavior, which correlated to a decreased expression of the satiety gene and an increased expression of the hunger gene. We conclude that the zebrafish embryo is a useful model for studying estrogenicity, obesity, and thyroid hormone function to understand the endocrine disruption activity of environmental pollutants.

ISBN: 9798380142434Subjects--Topical Terms:

657580
Bioengineering.
Subjects--Index Terms:

Agonists

Environmental Pollutants Alter Estrogen and Thyroid Hormone Response and Appetite Control in Zebrafish.
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300 $a 151 p.
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500 $a Advisor: Bondesson, Maria.
502 $a Thesis (Ph.D.)--Indiana University, 2023.
520 $a Many environmental pollutants are endocrine disruptors; chemicals that interfere with the body's hormones in the endocrine systems. In this thesis, endocrine disruption of estrogen and thyroid hormone signaling were investigated using zebrafish as a model system. A common pollutant is bisphenol A (BPA), an estrogenic endocrine disruptor, which has been suggested to act as an obesity inducing chemical or obesogen. BPA analogues have been synthesized to replace BPA, but they need to be meticulously studied for safety. We used transgenic estrogen reporter Tg (5xERE:GFP) zebrafish to study estrogenic effects of the bisphenols, and found that the BPA analogues BPA, BPAF, BPC, BPE and BPC-Cl have strong estrogenic activities, whereas BPS has a weak estrogenic activity. We further showed that exposure to BPAF and BPC-Cl increase endogenous estrogen 17beta-estradiol (E2) levels in zebrafish larvae, indicating that bisphenol exposures result in a feed-forward response that can further augment the estrogenic activity of these compounds.For thyroid hormone disruption, we evaluated the efficiency of a transgenic thyroid hormone reporter zebrafish to signal perturbations of the hypothalamus-pituitary-thyroid (HPT) axis. We tested 12 different chemicals with known effects on the HPT axis or thyroid hormone (T4) metabolism. We found that the fish correctly responded to exposure to T4 and T3 (the active form of T4) and to the herbicide pronamide and the steroid pregnenolone, which both are known to induce metabolization of T4 via the uridine diphosphate glucuronosyl transferase (UGT) pathways.Over the past few decades, obesity has drastically soared to epidemic levels. To study the obesogenic capacity of BPA and its analogues, the effect of bisphenol exposure on eating behavior and on the gene expression for hormones controlling hunger (ghrelin) and satiety (leptin) were examined. Zebrafish larvae were exposed to the bisphenols, followed by being fed a stained egg yolk powder for an hour. Exposures to BPA, BPAF, BPE, BPC, BPC-Cl and BPS, resulted in increased amounts of food in the gut of the larvae. We further found that leptin mRNA expression was downregulated with the increasing concentrations of BPA, BPAF and BPC-Cl, whereas ghrelin mRNA expression was upregulated by BPC-Cl exposure. Thus, bisphenol exposures resulted in an augmented eating behavior, which correlated to a decreased expression of the satiety gene and an increased expression of the hunger gene. We conclude that the zebrafish embryo is a useful model for studying estrogenicity, obesity, and thyroid hormone function to understand the endocrine disruption activity of environmental pollutants.
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650 4 $a Toxicology. $3 556884
650 4 $a Developmental biology. $3 592588
653 $a Agonists
653 $a Bisphenols
653 $a ELISA
653 $a Estrogen receptor
653 $a Estrogen reporter cells
653 $a Transgenic fish
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690 $a 0383
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710 2 $a Indiana University. $b Intelligent Systems Engineering. $3 3685331
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793 $a English
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