Hayashi M, Maruo T, Matsuo H, Mochizuki M
Department of Obstetrics and Gynecology, Kobe University School of Medicine.
Nihon Naibunpi Gakkai Zasshi. 1987 Oct 20;63(10):1231-40. doi: 10.1507/endocrine1927.63.10_1231.
In order to elucidate the mechanism of thyroid hormone action on the ovary, direct effects of L-thyroxine (T4) or L-triiodothyronine (T3) on steroidogenic enzyme induction were investigated in vitro using a monolayer culture system of porcine granulosa cells obtained from small follicles. The cells were cultured in the absence or presence of porcine FSH (20ng/ml) for 6 days, with or without T4 or T3, under sparsely (4%) serum supplemented condition. The mechanism of thyroid hormone action on the granulosa cells was studied by testing the capability of thyroid hormone to enhance the steroidogenesis in response to exogenously provided substrates. Concomitant treatment with FSH (20ng/ml) and T4 (10(-7) M) caused a further increased production of progesterone in response to the addition of pregnenolone compared to that in the absence of pregnenolone. The same treatment with FSH and T4 also caused a further increased production of estrone in response to the addition of androstenedione. Concomitant treatment with 10(-9) MT3 demonstrated similar stimulatory effects on the steroidogenesis in cultured granulosa cells. T4 or T3 alone without FSH was incapable of exhibiting these stimulatory effects. Furthermore, aromatase activity in cultured granulosa cells assessed by the release of tritiated water from [1 beta-3H, 4-14C] androstenedione was significantly higher in the cells treated concomitantly with FSH (20ng/ml) and T4 (10(-7) M) than that in the cells treated with FSH alone. These results suggest that thyroid hormone synergizes with FSH and increases FSH-mediated induction of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and aromatase activity in immature granulosa cells. Since the effective dose of T4 and T3 observed in our studies is in the physiological range of circulating total levels of T4 and T3, it can be concluded that the synergism between FSH and thyroid hormone is of physiological importance to the full expression of FSH actions in the functional differentiation of immature granulosa cells.
为阐明甲状腺激素对卵巢的作用机制，我们使用从小卵泡获取的猪颗粒细胞单层培养系统，在体外研究了L-甲状腺素（T4）或L-三碘甲状腺原氨酸（T3）对类固醇生成酶诱导的直接影响。细胞在添加或不添加猪促卵泡素（FSH，20ng/ml）的情况下培养6天，培养条件为添加或不添加T4或T3，且血清浓度较低（4%）。通过检测甲状腺激素增强对外源提供底物的类固醇生成的能力，研究甲状腺激素对颗粒细胞的作用机制。与未添加孕烯醇酮相比，同时用FSH（20ng/ml）和T4（10⁻⁷M）处理，在添加孕烯醇酮后孕酮产量进一步增加。FSH和T4的相同处理在添加雄烯二酮后也使雌酮产量进一步增加。用10⁻⁹M T3同时处理对培养的颗粒细胞类固醇生成表现出类似的刺激作用。单独的T4或T3而无FSH不能表现出这些刺激作用。此外，在同时用FSH（20ng/ml）和T4（10⁻⁷M）处理的细胞中，通过[1β-³H, 4-¹⁴C]雄烯二酮释放氚化水评估的培养颗粒细胞中的芳香化酶活性显著高于仅用FSH处理的细胞。这些结果表明，甲状腺激素与FSH协同作用，增加FSH介导的未成熟颗粒细胞中3β-羟基类固醇脱氢酶（3β-HSD）和芳香化酶活性的诱导。由于我们研究中观察到的T4和T3有效剂量处于循环中T4和T3总水平的生理范围内，因此可以得出结论，FSH与甲状腺激素之间的协同作用对于FSH在未成熟颗粒细胞功能分化中的作用的充分表达具有生理重要性。
