Kieffer J D, Ross D S, Shupnik M A, Ridgway E C
Endocrinology. 1985 Oct;117(4):1418-23. doi: 10.1210/endo-117-4-1418.
We have recently documented the spontaneous development of a mouse pituitary tumor line (MGH 101A) secreting only the alpha-subunit of the glycoprotein hormones. Secretion of alpha-subunit by MGH 101A was not inhibited by either physiological or pharmacological levels of thyroid hormones. The present study demonstrates that combined treatment with bromocriptine and pharmacological doses of T4 for 1 month significantly decreased both tumor growth and alpha-subunit secretion of MGH 101A in thyroidectomized host mice. Either treatment alone was ineffective. The fall in plasma alpha-subunit concentrations after the combined treatment was probably due to the inhibition of tumor growth, since the decreases in plasma alpha-subunit levels and tumor weights were quantitatively similar, and there was no significant change in tumor steady state concentrations of alpha-subunit mRNA. In two of three experiments, the combined treatment resulted in a significant fall in tumor total DNA concentrations; this suggests that decreased tumor growth was at least in part due to inhibition of tumor cell replication. To compare the effects of the various treatments on the pure alpha-subunit-producing pituitary tumor with their effects on non-tumorous pituitary, we also measured secretion of TSH and PRL into plasma by the host pituitary. Treatment with T4 alone profoundly suppressed plasma concentrations of TSH and significantly reduced plasma PRL levels compared to levels in the thyroidectomized controls. Surprisingly, both thyroidectomized and euthyroid tumor hosts treated with bromocriptine alone showed no suppression of plasma PRL levels. However, combined treatment with bromocriptine and pharmacological doses of T4 resulted in plasma PRL concentrations significantly lower than those after treatment with T4 alone. Thus, the tumor and nontumorous host pituitaries differed in their responses to T4 alone. However, the two tissues were similar in their responses to bromocriptine alone and to combined treatment with bromocriptine and T4. We conclude that combined treatment with T4 and bromocriptine inhibited the growth and secretion of the pure alpha-subunit-secreting tumor MGH 101A. The data on PRL secretion by the host pituitary suggest that T4 may have acted by enhancing the function of dopamine receptors.
我们最近记录了一种小鼠垂体肿瘤细胞系（MGH 101A）的自发形成，该细胞系仅分泌糖蛋白激素的α亚基。甲状腺激素的生理或药理水平均不能抑制MGH 101A分泌α亚基。本研究表明，在甲状腺切除的宿主小鼠中，用溴隐亭和药理剂量的T4联合治疗1个月可显著降低MGH 101A的肿瘤生长和α亚基分泌。单独使用任何一种治疗方法均无效。联合治疗后血浆α亚基浓度的下降可能是由于肿瘤生长受到抑制，因为血浆α亚基水平和肿瘤重量的下降在数量上相似，且肿瘤α亚基mRNA的稳态浓度没有显著变化。在三个实验中的两个实验中，联合治疗导致肿瘤总DNA浓度显著下降；这表明肿瘤生长的降低至少部分是由于肿瘤细胞复制受到抑制。为了比较各种治疗方法对纯α亚基分泌性垂体肿瘤的影响及其对非肿瘤性垂体的影响，我们还测量了宿主垂体向血浆中分泌TSH和PRL的情况。与甲状腺切除的对照组相比，单独用T4治疗可显著抑制血浆TSH浓度，并显著降低血浆PRL水平。令人惊讶的是，单独用溴隐亭治疗的甲状腺切除和甲状腺功能正常的肿瘤宿主，其血浆PRL水平均未受到抑制。然而，溴隐亭和药理剂量的T4联合治疗导致血浆PRL浓度显著低于单独用T4治疗后的浓度。因此，肿瘤性和非肿瘤性宿主垂体对单独T4的反应不同。然而，这两种组织对单独溴隐亭以及溴隐亭和T4联合治疗的反应相似。我们得出结论，T4和溴隐亭联合治疗可抑制纯α亚基分泌肿瘤MGH 101A的生长和分泌。宿主垂体PRL分泌的数据表明，T4可能通过增强多巴胺受体的功能发挥作用。
