Hormone Disruption by PBDEs in Adult Male Sport Fish Consumers
Hormone Disruption by PBDEs in Adult Male Sport Fish Consumers
Background: Persistent pollutants, such as polychlorinated biphenyls (PCBs), affect endocrine function. Human exposure to polybrominated diphenyl ethers (PBDEs), which are similar in structure to PCBs, has increased recently, but health effects have not been well studied.
Objectives: Our goal in this study was to determine whether PBDE body burdens are related to thyroid and steroid hormone levels, thyroid antibodies, and thyroid disease in a cohort of frequent and infrequent adult male sport fish consumers.
Methods: We tested serum from 405 adult males for PBDE congeners, PCB congeners, testosterone, sex-hormone-binding globulin (SHBG), SHBG-bound testosterone, thyroglobulin antibodies, and the thyroid hormones thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG). We collected data on demographics, fish consumption, medical diseases, and medication use.
Results: The median sum of PBDEs was 38 ng/g lipid. In 308 men without thyroid disease or diabetes, PBDEs were positively related to measures of T4 and reverse T3 and inversely related to total T3 and TSH. PBDEs were positively related to the percentage of T4 bound to albumin, and inversely related to the percentage of T4 bound to TBG. Associations of BDE congeners with hormones varied. BDE-47 was positively associated with testosterone levels. Participants with PBDEs over the 95th percentile were more likely to have thyroglobulin antibodies, although high PBDE exposure was not associated with thyroid disease. PBDE effects were independent of PCB exposure and sport fish consumption.
Conclusions: PBDE exposure, at levels comparable with those of the general U.S. population, was associated with increased thyroglobulin antibodies and increased T4 in adult males.
Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in electronic equipment, home furnishings, textiles, and construction materials. They are similar to polychlorinated biphenyls (PCBs) in structure and in their persistence and bioaccumulative properties (Birnbaum and Staskal 2004). Over the last 20 years, PBDE levels have increased in human samples, whereas PCBs have declined (Schecter et al. 2005).
Because PBDEs are similar in structure to thyroxine (T4) and triiodothyronine (T3) (Hamers et al. 2006), concerns have been raised regarding their effect on thyroid function, which is regulated by the hypothalamo-pituitary-thyroid axis and influences development and gene expression in vertebrates (Zoeller et al. 2007). Reduction of circulating thyroid hormone is compensated for by release of thyroid-releasing hormone from the hypothalamus, which in turn increases thyroid-stimulating hormone (TSH) release from the pituitary, ultimately stimulating thyroid hormone production. T4 and T3 are transported to peripheral tissues bound to proteins, primarily T4-binding globulin (TBG), but also to albumin and transthyretin (TTR). TBG production is stimulated by estrogen and inhibited by testosterone. T4 is the major hormone produced by the thyroid. Some T3 is produced directly by the thyroid, but most is derived from peripheral deiodination of T4. T3 and T4 are primarily metabolized by deiodination to diiodothyronine and reverse T3 (rT3), with some metabolism through glucuronidation, sulfonation, and other pathways. This complex system is vulnerable to disruption by a variety of chemicals through changes in hormone production, transport, and/or metabolism (Zoeller et al. 2007).
Biologic effects of PBDEs in rodents are similar to those of PCBs, with increased risks for reproductive and endocrine disruption (Ellis-Hutchings et al. 2006; Lilienthal et al. 2006; Stoker et al. 2004; Zhou et al. 2002), and neurodevelopmental problems (Kuriyama et al. 2005). In humans, PCBs have been associated with disruption of thyroid hormone homeostasis (Langer et al. 2007; Persky et al. 2001; Turyk et al. 2007), but the effects of PBDEs on thyroid hormones have been investigated only in a few smaller studies (Bloom et al. 2008; Hagmar et al. 2001; Julander et al. 2005; Yuan et al. 2008).
In 2001, we reported that PCBs were associated with lower levels of T4 and free T4 index in women and T4 and sex-hormone-binding globulin (SHBG)-bound testosterone in men from a cohort of frequent and infrequent Great Lakes fish consumers (Persky et al. 2001). In 2003, we invited participants from the original cohort to participate in a follow-up study to explore potential mechanisms by which PBDEs, PCBs, and p,p′-diphenyl-dichloroethene (DDE) might be affecting thyroid hormone balance. In addition to the standard hormones (free and total T4 and T3, as well as TSH), we explored via additional laboratory parameters specific mechanisms of action suggested by laboratory studies, such as changes in transport by serum-binding proteins (Hallgren et al. 2001; Hamers et al. 2006) and increase in thyroglobulin antibodies (Langer et al. 2007). In this study we explored the relationship of PBDE exposure with hormone homeostasis, thyroglobulin antibodies, and thyroid disease in men. Associations of thyroid hormones with PCB congeners and DDE will be reported separately.
Abstract and Introduction
Abstract
Background: Persistent pollutants, such as polychlorinated biphenyls (PCBs), affect endocrine function. Human exposure to polybrominated diphenyl ethers (PBDEs), which are similar in structure to PCBs, has increased recently, but health effects have not been well studied.
Objectives: Our goal in this study was to determine whether PBDE body burdens are related to thyroid and steroid hormone levels, thyroid antibodies, and thyroid disease in a cohort of frequent and infrequent adult male sport fish consumers.
Methods: We tested serum from 405 adult males for PBDE congeners, PCB congeners, testosterone, sex-hormone-binding globulin (SHBG), SHBG-bound testosterone, thyroglobulin antibodies, and the thyroid hormones thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG). We collected data on demographics, fish consumption, medical diseases, and medication use.
Results: The median sum of PBDEs was 38 ng/g lipid. In 308 men without thyroid disease or diabetes, PBDEs were positively related to measures of T4 and reverse T3 and inversely related to total T3 and TSH. PBDEs were positively related to the percentage of T4 bound to albumin, and inversely related to the percentage of T4 bound to TBG. Associations of BDE congeners with hormones varied. BDE-47 was positively associated with testosterone levels. Participants with PBDEs over the 95th percentile were more likely to have thyroglobulin antibodies, although high PBDE exposure was not associated with thyroid disease. PBDE effects were independent of PCB exposure and sport fish consumption.
Conclusions: PBDE exposure, at levels comparable with those of the general U.S. population, was associated with increased thyroglobulin antibodies and increased T4 in adult males.
Introduction
Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in electronic equipment, home furnishings, textiles, and construction materials. They are similar to polychlorinated biphenyls (PCBs) in structure and in their persistence and bioaccumulative properties (Birnbaum and Staskal 2004). Over the last 20 years, PBDE levels have increased in human samples, whereas PCBs have declined (Schecter et al. 2005).
Because PBDEs are similar in structure to thyroxine (T4) and triiodothyronine (T3) (Hamers et al. 2006), concerns have been raised regarding their effect on thyroid function, which is regulated by the hypothalamo-pituitary-thyroid axis and influences development and gene expression in vertebrates (Zoeller et al. 2007). Reduction of circulating thyroid hormone is compensated for by release of thyroid-releasing hormone from the hypothalamus, which in turn increases thyroid-stimulating hormone (TSH) release from the pituitary, ultimately stimulating thyroid hormone production. T4 and T3 are transported to peripheral tissues bound to proteins, primarily T4-binding globulin (TBG), but also to albumin and transthyretin (TTR). TBG production is stimulated by estrogen and inhibited by testosterone. T4 is the major hormone produced by the thyroid. Some T3 is produced directly by the thyroid, but most is derived from peripheral deiodination of T4. T3 and T4 are primarily metabolized by deiodination to diiodothyronine and reverse T3 (rT3), with some metabolism through glucuronidation, sulfonation, and other pathways. This complex system is vulnerable to disruption by a variety of chemicals through changes in hormone production, transport, and/or metabolism (Zoeller et al. 2007).
Biologic effects of PBDEs in rodents are similar to those of PCBs, with increased risks for reproductive and endocrine disruption (Ellis-Hutchings et al. 2006; Lilienthal et al. 2006; Stoker et al. 2004; Zhou et al. 2002), and neurodevelopmental problems (Kuriyama et al. 2005). In humans, PCBs have been associated with disruption of thyroid hormone homeostasis (Langer et al. 2007; Persky et al. 2001; Turyk et al. 2007), but the effects of PBDEs on thyroid hormones have been investigated only in a few smaller studies (Bloom et al. 2008; Hagmar et al. 2001; Julander et al. 2005; Yuan et al. 2008).
In 2001, we reported that PCBs were associated with lower levels of T4 and free T4 index in women and T4 and sex-hormone-binding globulin (SHBG)-bound testosterone in men from a cohort of frequent and infrequent Great Lakes fish consumers (Persky et al. 2001). In 2003, we invited participants from the original cohort to participate in a follow-up study to explore potential mechanisms by which PBDEs, PCBs, and p,p′-diphenyl-dichloroethene (DDE) might be affecting thyroid hormone balance. In addition to the standard hormones (free and total T4 and T3, as well as TSH), we explored via additional laboratory parameters specific mechanisms of action suggested by laboratory studies, such as changes in transport by serum-binding proteins (Hallgren et al. 2001; Hamers et al. 2006) and increase in thyroglobulin antibodies (Langer et al. 2007). In this study we explored the relationship of PBDE exposure with hormone homeostasis, thyroglobulin antibodies, and thyroid disease in men. Associations of thyroid hormones with PCB congeners and DDE will be reported separately.
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