Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease.
OBJECTIVE
To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms.


METHODS
Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg·kg(-1)·d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR.


RESULTS
The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice.


CONCLUSIONS
Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.
1] Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China [2] Shandong Clinical Medical Center of Endocrinology and Metabolism, Ji-nan 250011, China [3] Department of Endocrinology, Taizhou First Peoples' Hospital, Taizhou 318000, China.
Hu
H
Cai
Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China.
Zhe
Z
Wang
1] Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China [2] Shandong Clinical Medical Center of Endocrinology and Metabolism, Ji-nan 250011, China [3] Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan 250011, China.
Hai-qing
HQ
Zhang
Department of Pharmacology, Shandong University of Traditional Chinese Medicine, Ji-nan 250011, China.
Fu-rong
FR
Wang
1] Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China [2] Shandong Clinical Medical Center of Endocrinology and Metabolism, Ji-nan 250011, China [3] Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan 250011, China.
Chun-xiao
CX
Yu
1] Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China [2] Shandong Clinical Medical Center of Endocrinology and Metabolism, Ji-nan 250011, China [3] Department of Neurology, Hospital affiliated to Shandong University of Traditional Chinese Medicine, Ji-nan 250011, China.
Feng-xia
FX
Zhang
1] Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China [2] Shandong Clinical Medical Center of Endocrinology and Metabolism, Ji-nan 250011, China [3] Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan 250011, China.
Ling
L
Gao
Department of Pharmacy, Shandong Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China.
Jian
J
Zhang
1] Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Ji-nan 250011, China [2] Shandong Clinical Medical Center of Endocrinology and Metabolism, Ji-nan 250011, China [3] Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Ji-nan 250011, China.
Jia-jun
JJ
Zhao
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004144:Diosgenin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006042:Goiter / Q000188:drug therapy / Q000473:pathology; D006111:Graves Disease / Q000188:drug therapy* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects*
D004144:Diosgenin