Denereaz N, Lemarchand-Beraud T
Department of Internal Medicine, University Hospital, Lausanne, Switzerland.
Endocrinology. 1995 Apr;136(4):1694-700. doi: 10.1210/endo.136.4.7895680.
TSH initiates its action by binding to specific membrane receptors' thyroid cells and induces activation of the adenylate cyclase-cAMP cascade. The factors involved in the regulation of TSH receptors are poorly known, except for the TSH dose-dependent regulatory effect. The fact that the thyroid gland of Graves' patients has a normal density of TSH receptors with suppressed TSH and high T4 and T3 levels suggests a modulatory role of thyroid hormones on TSH receptors. To evaluate this hypothesis, the density of TSH receptors and the activity of adenylate cyclase were determined in the thyroid membranes from hyperthyroid and hypothyroid adult male rats; they were rendered hyperthyroid either with bovine TSH, TRH, or T3 for 7 days and hypothyroid by propylthiouracil treatment or by hypophysectomy. NaCl was given to the control group. Plasma T4, T3, and TSH were also quantified. Bovine TSH and TRH treatments induced mild hyperthyroidism with a small goiter and a 50% reduction in the density of TSH receptors due to hyperstimulation of the gland by either exogenous or endogenous high TSH levels. Severe hyperthyroidism caused by T3 treatment resulted in low T4, high T3, and suppressed TSH thyrocyte stimulation; it was associated with a significant increase in the number of TSH receptors (29.6 +/- 2.3 vs. control 17.9 +/- 1.7 mU TSH/mg protein). These last results suggest a putative positive effect of T3 on TSH receptors. To confirm this effect, hypothyroid rats were investigated. Severe primary hypothyroidism due to propylthiouracil treatment was associated with a large goiter, high plasma TSH levels (11.8 +/- 1.2 vs. control 1.5 +/- 0.1 mU TSH/ml), low plasma T4 and T3, and a 70% reduction in TSH receptors, confirming the down-regulatory effect of high TSH on the thyroid cell. However, in hypophysectomized rats, a 45% reduction in the density of TSH receptors was also observed in the absence of TSH. Injections of either TSH or T3 to these hypophysectomized rats restored a normal number of TSH-binding sites, and simultaneous TSH and T3 treatments resulted in a mildly additive effect in the number of TSH receptors, which was slightly greater than that of the controls. No important changes were found in the adenylate cyclase activity in the thyroid membrane preparations from hyperthyroid and hypothyroid rats despite variations in the density of TSH receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
促甲状腺激素（TSH）通过与甲状腺细胞的特定膜受体结合来启动其作用，并诱导腺苷酸环化酶 - cAMP级联反应的激活。除了TSH剂量依赖性调节作用外，参与TSH受体调节的因素鲜为人知。格雷夫斯病患者的甲状腺具有正常密度的TSH受体，但TSH受到抑制，T4和T3水平升高，这一事实表明甲状腺激素对TSH受体具有调节作用。为了评估这一假设，测定了成年雄性甲亢和甲减大鼠甲状腺膜中TSH受体的密度以及腺苷酸环化酶的活性；通过给予牛TSH、促甲状腺激素释放激素（TRH）或T3 7天使大鼠甲亢，通过丙硫氧嘧啶治疗或垂体切除使大鼠甲减。对照组给予氯化钠。还对血浆T4、T3和TSH进行了定量。牛TSH和TRH治疗诱导轻度甲亢，伴有小甲状腺肿，由于外源性或内源性高TSH水平对腺体的过度刺激，TSH受体密度降低50%。T3治疗引起的严重甲亢导致T4降低、T3升高以及TSH对甲状腺细胞刺激的抑制；这与TSH受体数量显著增加有关（29.6±2.3对对照组17.9±1.7 mU TSH/mg蛋白）。这些最后的结果表明T3对TSH受体有假定的正向作用。为了证实这一作用，对甲减大鼠进行了研究。丙硫氧嘧啶治疗导致的严重原发性甲减与大甲状腺肿、高血浆TSH水平（11.8±1.2对对照组1.5±0.1 mU TSH/ml）、低血浆T4和T3以及TSH受体减少70%有关，证实了高TSH对甲状腺细胞的下调作用。然而，在垂体切除的大鼠中，在没有TSH的情况下也观察到TSH受体密度降低了45%。向这些垂体切除的大鼠注射TSH或T3可恢复正常数量的TSH结合位点，同时给予TSH和T3治疗在TSH受体数量上产生轻度累加效应，略大于对照组。尽管TSH受体密度有所变化，但甲亢和甲减大鼠甲状腺膜制剂中的腺苷酸环化酶活性未发现重要变化。（摘要截取自400字）
