Goldring S R, Dayer J M, Krane S M
Calcif Tissue Int. 1979;29(3):193-200. doi: 10.1007/BF02408080.
Cells dispersed from human giant cell tumors of bone and grown in monolayer culture increase intracellular cyclic AMP (cAMP) when incubated with parathyroid hormone (PTH) or prostaglandin E2 (PGE2). When cells are continuously exposed to PTH, cAMP levels increase acutely but then decrease rapidly to pretreatment values despite continued presence of hormone or addition of new hormone. Preincubation of cells with PTH for periods as short as 10 min results in a decrease in the capacity of cells to increase cAMP content when re-exposed to maximal stimulatory concentrations of PTH. The decrease in the magnitude of the PTH-induced cAMP response observed in cells pretreated with this hormone is dependent on the concentration of PTH present during the preincubation. The loss of cAMP response in cells pretreated with either PGE2 or PTH is hormone specific in that cells made refractory by pretreatment with one hormone still increase cAMP content when exposed to the other. Although the cells are not releasing measurable amounts of prostaglandins into the medium, pretreatment with indomethacin results in an increase in the magnitude of the cAMP response to PGE2. The PTH-induced cAMP response is not affected by indomethacin pretreatment. The loss of PTH responsiveness produced by hormone preincubation is consistent with the phenomenon of "down-regulation" observed with ligand-receptor interactions in a variety of tissues.
从人骨巨细胞瘤中分离并在单层培养中生长的细胞，在与甲状旁腺激素（PTH）或前列腺素E2（PGE2）孵育时，细胞内的环磷酸腺苷（cAMP）会增加。当细胞持续暴露于PTH时，cAMP水平会急剧升高，但随后会迅速下降至预处理值，尽管激素持续存在或添加了新的激素。用PTH对细胞进行短至10分钟的预孵育，会导致细胞在再次暴露于最大刺激浓度的PTH时，增加cAMP含量的能力下降。在用这种激素预处理的细胞中观察到的PTH诱导的cAMP反应幅度的降低，取决于预孵育期间存在的PTH浓度。用PGE2或PTH预处理的细胞中cAMP反应的丧失是激素特异性的，因为用一种激素预处理而变得不应答的细胞，在暴露于另一种激素时仍会增加cAMP含量。尽管细胞没有向培养基中释放可测量量的前列腺素，但用吲哚美辛预处理会导致对PGE2的cAMP反应幅度增加。吲哚美辛预处理不会影响PTH诱导的cAMP反应。激素预孵育导致的PTH反应性丧失与在多种组织中观察到的配体-受体相互作用的“下调”现象一致。
