Schwartz J, Pham T, Rao A, Funder J W
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Am J Physiol. 1991 Jun;260(6 Pt 1):E905-9. doi: 10.1152/ajpendo.1991.260.6.E905.
Although exposure to arginine vasopressin (AVP) has been reported to induce anterior pituitary corticotrophs to bind and become responsive to corticotropin-releasing factor (CRF), the identity of these inducible CRF target cells is unknown. Such cells may themselves be the AVP-responsive corticotrophs or other cells that become CRF targets secondary to a paracrine signal from AVP target cells. The present study used a cytotoxin (Cx), specific for CRF target cells, that eliminates responses of treated cells to a subsequent challenge with CRF but leaves responses to AVP intact. We hypothesized that, if AVP target corticotrophs themselves become CRF targets, then the addition of AVP during treatment with Cx should render these cells susceptible to the cytotoxin and should eliminate the response to subsequent AVP as well. Ovine pituitary cells were chosen for the study because they respond more robustly than rat cells to AVP. Pretreatment of ovine pituitary cells with Cx (400 pM) or Cx plus AVP (10 nM) eliminated the adrenocorticotropic hormone (ACTH) secretory response to CRF (10 nM), as assessed 3 days later. Cx alone also reduced the secretory response to AVP from 23.9 +/- 3.4 to 11.5 +/- 1.9 ng ACTH/3 h (P less than 0.05). However, pretreatment with AVP (10 nM) plus Cx caused no further reduction in the secretory response to AVP (10.1 +/- 2.6 ng ACTH/3 h). These data suggest that, if AVP induces erstwhile non-CRF target cells to become CRF targets, then these induced cells are not themselves initially AVP target corticotrophs.
尽管已有报道称，接触精氨酸加压素（AVP）可诱导垂体前叶促肾上腺皮质激素细胞结合促肾上腺皮质激素释放因子（CRF）并对其产生反应，但这些可诱导的CRF靶细胞的身份尚不清楚。这类细胞可能本身就是对AVP有反应的促肾上腺皮质激素细胞，或者是因来自AVP靶细胞的旁分泌信号而成为CRF靶细胞的其他细胞。本研究使用了一种对CRF靶细胞具有特异性的细胞毒素（Cx），它可消除处理过的细胞对随后CRF刺激的反应，但对AVP的反应保持不变。我们推测，如果AVP靶促肾上腺皮质激素细胞本身成为CRF靶细胞，那么在用Cx处理期间添加AVP应会使这些细胞对细胞毒素敏感，并应消除对随后AVP的反应。本研究选择绵羊垂体细胞，因为它们对AVP的反应比大鼠细胞更强烈。用Cx（400 pM）或Cx加AVP（10 nM）预处理绵羊垂体细胞3天后，可消除对CRF（10 nM）的促肾上腺皮质激素（ACTH）分泌反应。单独使用Cx也将对AVP的分泌反应从23.9±3.4降至11.5±1.9 ng ACTH/3 h（P<0.05）。然而，用AVP（10 nM）加Cx预处理并未使对AVP的分泌反应进一步降低（10.1±2.6 ng ACTH/3 h）。这些数据表明，如果AVP诱导以前的非CRF靶细胞成为CRF靶细胞，那么这些诱导细胞最初本身不是AVP靶促肾上腺皮质激素细胞。
