Abstract
A role for dietary phytoestrogens in preventing thyroid disease remains controversial. Previously, we showed that thyroid-targeted
overexpression of the proto-oncogene PTTG-binding factor (PBF) induced striking thyroid gland enlargement in transgenic mice (PBFTg)1
.
We have now investigated whether PBF-Tg mice fed on diets with
different amounts of phytoestrogens affect goitrogenesis and the development of hyperplastic lesions.
PBF-Tg mice fed on a low-phytoestrogen (PE) diet showed an
approximate doubling of thyroid weight (mean = 5.9 – 0.9 mg; n = 75)
at 6 weeks of age compared to PBF-Tg mice fed a high-PE diet
(3.3 – 0.8 mg; n = 98; p < 0.0001). In contrast, the thyroid weight of wildtype (WT) mice increased only marginally when fed the low-PE diet
(mean = 2.17 – 0.5 mg; n = 60) compared to the high-PE diet (1.8 – 0.4
mg; n = 68). This increase in thyroid weight was not related to differences in body weight (25.0 – 1.9g v 24.7 – 2.4g; p = 0.3) or thyroid
function, as measured by serum analysis of T3 (172.7 – 25.9 versus
154.1 – 46.9 ng/dL, p = 0.5), and T4 levels (2.7 – 0.7 versus 3.2 – 1.2 lg/
dL, p = 0.5), between PBF-Tg mice fed either the low- or high-PE diet,
respectively. Analysis of mRNA showed a significant increase in cyclin D1 expression (1.6 – 0.2-fold, p = 0.008), as well as mRNAs encoding for growth factor receptors known to induce thyroid cell
proliferation, such as PDGFR (1.6 – 0.3-fold, p = 0.0001), FGFR2
(1.5 – 0.2-fold, p = 0.0001), and KDR (1.4 – 0.2-fold, p = 0.003), in thyroids from PBF-Tg mice fed the low-PE diet compared to those on the
high-PE diet. Furthermore, histological examination detected a
greater frequency of focal hyperplastic lesions in thyroids from 12-
month-old PBF-Tg mice fed the low-PE diet (83% of mice; n = 10/12)
versus the high PE diet (8.3% of mice; n = 1/12; p < 0.0001). No hyperplastic lesions were detected in thyroids from age-matched WT
mice (n = 0/12). Positive immunostaining with antibodies targeted to
Rad6, Ung1, and Trex1 also indicated extensive DNA damage within
hyperplastic lesions.
These results suggest that phytoestrogens can influence goitrogenesis and hyperplasia in PBF-Tg mice, thus implicating a role for
phytoestrogens in modulating thyroid disease. 1
Read ML et al., (2011)
Cancer Research 71(19), 6153–6164.
overexpression of the proto-oncogene PTTG-binding factor (PBF) induced striking thyroid gland enlargement in transgenic mice (PBFTg)1
.
We have now investigated whether PBF-Tg mice fed on diets with
different amounts of phytoestrogens affect goitrogenesis and the development of hyperplastic lesions.
PBF-Tg mice fed on a low-phytoestrogen (PE) diet showed an
approximate doubling of thyroid weight (mean = 5.9 – 0.9 mg; n = 75)
at 6 weeks of age compared to PBF-Tg mice fed a high-PE diet
(3.3 – 0.8 mg; n = 98; p < 0.0001). In contrast, the thyroid weight of wildtype (WT) mice increased only marginally when fed the low-PE diet
(mean = 2.17 – 0.5 mg; n = 60) compared to the high-PE diet (1.8 – 0.4
mg; n = 68). This increase in thyroid weight was not related to differences in body weight (25.0 – 1.9g v 24.7 – 2.4g; p = 0.3) or thyroid
function, as measured by serum analysis of T3 (172.7 – 25.9 versus
154.1 – 46.9 ng/dL, p = 0.5), and T4 levels (2.7 – 0.7 versus 3.2 – 1.2 lg/
dL, p = 0.5), between PBF-Tg mice fed either the low- or high-PE diet,
respectively. Analysis of mRNA showed a significant increase in cyclin D1 expression (1.6 – 0.2-fold, p = 0.008), as well as mRNAs encoding for growth factor receptors known to induce thyroid cell
proliferation, such as PDGFR (1.6 – 0.3-fold, p = 0.0001), FGFR2
(1.5 – 0.2-fold, p = 0.0001), and KDR (1.4 – 0.2-fold, p = 0.003), in thyroids from PBF-Tg mice fed the low-PE diet compared to those on the
high-PE diet. Furthermore, histological examination detected a
greater frequency of focal hyperplastic lesions in thyroids from 12-
month-old PBF-Tg mice fed the low-PE diet (83% of mice; n = 10/12)
versus the high PE diet (8.3% of mice; n = 1/12; p < 0.0001). No hyperplastic lesions were detected in thyroids from age-matched WT
mice (n = 0/12). Positive immunostaining with antibodies targeted to
Rad6, Ung1, and Trex1 also indicated extensive DNA damage within
hyperplastic lesions.
These results suggest that phytoestrogens can influence goitrogenesis and hyperplasia in PBF-Tg mice, thus implicating a role for
phytoestrogens in modulating thyroid disease. 1
Read ML et al., (2011)
Cancer Research 71(19), 6153–6164.
| Original language | English |
|---|---|
| Article number | P196 |
| Journal | Thyroid |
| Volume | 22(1_Suppl) |
| Publication status | Published - 2012 |
| Event | 82nd Annual Meeting of the American Thyroid Association - Quebec City, Canada Duration: 19 Sept 2012 → 23 Sept 2012 |
