Testosterone and estradiol modulate TSH-binding in the thyrocytes of Wistar rats: influence of age and sex

Testosterone and estradiol modulate TSH-binding in the thyrocytes of Wistar rats: influence of age and sex
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DOI:
10.1016/s0960-0760(01)00107-8
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发表时间:
2001-10-01
影响因子:
4.1
通讯作者:
Aruldhas, MM
Aruldhas, MM
中科院分区:
生物学2区
文献类型:
--
作者:
Banu, KS;Govindarajulu, P;Aruldhas, MM

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年龄和性别是影响甲状腺病理生理的重要因素。虽然已知性类固醇可增强促甲状腺激素(TSH)mRNA的表达和甲状腺肿瘤的发病率,但在正常生理条件下,尚无关于其对TSH作用的影响的报道。在本研究中,睾酮(T)和雌二醇(E-2)对甲状腺TSH受体(TSH-R)浓度的影响,和TSH结合甲状腺细胞(体外)在未成年和成年Wistar大鼠阐明。将未成熟(10天)和成年(120天)的雄性大鼠进行性腺切除(GDX),一组GDX大鼠用生理剂量的T治疗,另一组用E-2治疗。未成熟的GDX大鼠补充类固醇10天,成年大鼠补充类固醇30天。虽然未成熟大鼠在手术后立即开始补充类固醇,但成年大鼠在性腺切除术后10天开始。实验结束时处死大鼠。在体内条件下,性腺切除显著降低血清TSH和TSH-R浓度,在体外条件下显著降低[I-125]-TSH与甲状腺细胞的结合。雄性GDX大鼠补充T和雌性GDX大鼠补充E-2后,这些参数恢复正常。未成熟雄性大鼠的甲状腺细胞用线性增加剂量的TSH或T(6.25-800 ng/ml)激发,显示TSH结合的剂量依赖性增加。然而,未成熟的雌性大鼠甲状腺细胞与T的挑战表现出性别特异性的反应。虽然有一个线性增加,男性甲状腺细胞中的TSH结合,双相反应是明显的女性甲状腺细胞。在成年大鼠甲状腺细胞的情况下,T诱导雄性TSH结合的剂量依赖性变化,在12.5 ng T时达到峰值。此后,逐渐减少。相反,E-2抑制TSH结合成年雄性大鼠的甲状腺细胞。另一方面,E-2对女性甲状腺细胞中的TSH结合表现出明显的性别特异性刺激,而对男性甲状腺细胞中的TSH结合则表现出抑制作用。促甲状腺激素和性类固醇上调促甲状腺激素受体在未成年大鼠,而在成年大鼠甲状腺细胞的效果是双相的。它的结论是从目前的研究表明,性类固醇调节TSH结合在大鼠甲状腺细胞,这可能会根据动物的年龄和性别。(C)2001爱思唯尔科技有限公司版权所有。
Age and sex are important factors that influence thyroid pathophysiology. Though sex steroids are known to enhance thyrotropin (TSH) mRNA expression and incidence of thyroid tumours, there is no report on their effects on TSH action under normal physiological conditions. In the present study, the effects of testosterone (T) and estradiol (E-2) on thyroidal TSH-receptor (TSH-R) concentration, and TSH-binding to thyrocytes (in vitro) were elucidated in immature and mature Wistar rats. Immature (10 days old) and adult (120 days old) rats of either sex were gonadectomized (GDX) and one group of GDX rats was treated with physiological doses of T and another with E-2. Immature GDX rats were supplemented with the steroids for 10 days and adults were supplemented with the steroids for 30 days. While supplementation of steroids to immature rats was begun immediately after surgery, for adult rats it was started 10 days after gonadectomy. The rats were killed at the end of the experimental period. Gonadectomy significantly decreased serum TSH, and TSH-R concentration under in vivo condition and [I-125]-TSH binding to thyrocytes under in vitro conditions. Supplementation of T to male and E-2 to female GDX rats restored normality of the parameters. Thyrocytes of immature male rats challenged with linearly increasing doses of TSH or T (6.25-800 ng/ml) showed a dose-dependent increase in TSH-binding. However, thyrocytes of immature female rats challenged with T showed a gender-specific response. While there was a linear increase in TSH-binding in thyrocytes of males, a biphasic response was evident in thyrocytes of females. In the case of thyrocytes from adult rats, T induced a dose-dependent change in TSH-binding in males, which reached the peak in response to 12.5 ng T. and diminished thereafter. In contrast, E-2 was inhibitory to TSH-binding to thyrocytes of adult male rats. On the other hand, E-2 showed a clear gender-specific stimulation of TSH-binding in thyrocytes of females and an inhibition of the same in males. TSH and sex steroids upregulated TSH receptors in immature rats, whereas the effect was biphasic in adult rat thyrocytes. It is concluded from the present study that sex steroids modulate TSH-binding in rat thyrocytes, which may vary according to the age and sex of the animals. (C) 2001 Elsevier Science Ltd. All rights reserved.