J Korean Soc Endocrinol.  2006 Feb;21(1):32-39. 10.3803/jkes.2006.21.1.32.

Effect of High Concentration of Estradiol on Thyroid Specific Genes Expression and Cell Growth

Affiliations
  • 1Department of Internal Medicine, Dankook University, School of Medicine, Cheonam, Korea.

Abstract

BACKGROUND: Since various thyroid diseases have dominant prevalence in women, it has been suggested that female sex hormone have important role on thyroid cell physiology. Interestingly, many thyroid disorders are newly diagnosed or changed their course around the period of high estrogen status, such as pregnancy. In this study, we questioned whether high concentration of estrogen could modulate thyroid cell function.
METHODS
We treated normal rat thyroid FRTL-5 cell line with different time and concentration of estradiol. Using cell count, FACscan, and Northern blot analysis, we compared the changes of cell growth, cell cycle progression and thyroid specific genes expression. To evaluate the influence of thyroid stimulating hormone (TSH), all experiment was designed as two different sets, with (6H) or without TSH (5H).
RESULTS
The concentration of 10-1000 nM estradiol had definite stimulatory function on thyroid cell growth in 5H condition as concentration dependent manner. FACscan revealed the increased cell growths were related to G1/S progression. The Pax-8, TTF-1 and NIS gene expressions were dramatically increased in 10-1000 nM of estradiol, too. With TSH (6H), however, we could not find any cell growth stimulating effects with 10-1000 nM of estradiol.
CONCLUSION
High concentration of estradiol is one of important control factor for thyroid growth and thyroid specific genes expression, especially in 5H condition. It indicate that exposure to high concentration of female sex hormone, such as pregnancy, can be a direct stimulating factor to various thyroid function and related to autoimmune or nodular thyroid diseases around the period of pregnancy.


MeSH Terms

Animals
Blotting, Northern
Cell Count
Cell Cycle
Cell Line
Cell Physiological Phenomena
Estradiol*
Estrogens
Female
Gene Expression
Humans
Pregnancy
Prevalence
Rats
Thyroid Diseases
Thyroid Gland*
Thyrotropin
Estradiol
Estrogens
Thyrotropin

Figure

  • Fig. 1 Estradiol effects on FRTL-5 cell growth. Quiescent FRTL-5 cells were incubated with 10-1000 nM estradiol in the absence (5H) or presence (6H) of TSH for 1-5 days. Cell number was monitored every 24h for 5 consecutive days, and viable cell number is represented. The data are the mean ± SD of three independent experiments. *, P < 0.05 vs. control.

  • Fig. 2 Effect of high concentration of estradiol on cell cycle distribution of FRTL-5 cells. Flow cytometric histograms of FRTL-5 cells maintained in 5H medium for 72h, stimulated with different concentration of estradiol in the absence or presence of TSH are represented. Samples were collected after 24h of treatment for FACS analysis. The intensity of the propidium iodide statining vs. cell number is represented. The percentage of the cell cycle distribution is shown in Table 1.

  • Fig. 3 Effect of high concentration of estradiol on NIS RNA levels in FRTL-5 cells. Different time and concentration of estradiol in the absence (a) or presence (b) of TSH were compared. In contrast of continuous estradiol stimulation for 4 days (No.2-4), 2 days withdrawals after 2 days stimulations (No. 5-7) were also compared. Ability of estradiol to modulate NIS mRNA levels was significant in 5H condition (A). The ratio of the binding of each probe to β actin was calculated, and ratio of No.1 was set as 1 (B). Data are the mean ± SD of three different experiments, each performed in duplicate. *, P < 0.05 vs. control.

  • Fig. 4 Effect of high concentration of estradiol on Pax-8 RNA levels in FRTL-5 cells. Each number represents the different estradiol and TSH condition as indicated in Fig. 3 (A). The ratio of the binding of each probe to β actin was calculated, and ratio of No.1 was set as 1 (B). Data are the mean ± SD of three different experiments, each performed in duplicate. *, P < 0.05 vs. control.

  • Fig. 5 Effect of high concentration of estradiol on TTF-1 RNA levels in FRTL-5 cells. Each number represents the different estradiol and TSH condition as indicated in Fig. 3 (A). The ratio of the binding of each probe to β actin was calculated, and ratio of No.1 was set as 1 (B). Data are the mean ± SD of three different experiments, each performed in duplicate. *, P < 0.05 vs. control.


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