Schwartz J, Ray D W, Perez F M
Department of Obstetrics, Wake Forest University School of Medicine, Winston-Salem, N.C., USA.
Neuroendocrinology. 1999 Jan;69(1):34-43. doi: 10.1159/000054401.
In the normal anterior pituitary, intercellular interactions are important for the expression of hormones including adrenocorticotropin (ACTH). Leukemia inhibitory factor (LIF) is secreted by anterior pituitary cells and stimulates both basal and corticotropin-releasing hormone (CRH)-stimulated ACTH secretion in AtT20 cells. To determine the effects of LIF on normal pituitary cells, we measured the effects of LIF and an immunoneutralizing antiserum against LIF on ACTH secretion by cultured sheep anterior pituitary cells. In intact populations of anterior pituitary cells, LIF (10 nM) stimulated ACTH secretion (from 0.30 +/- 0.06 to 0.77 +/- 0.01 ng/well per 3 h) and antiserum to LIF (by itself) had no effect (0.29 +/- 0.05 ng/well per 3 h). In marked contrast, following pharmacological elimination of CRH-target cells, a condition known to disinhibit ACTH secretion, basal ACTH secretion was elevated (0.74 +/- 0.13 ng/well per 3 h); LIF produced no further stimulation (0.73 +/- 0.22 ng/well per 3 h) but immunoneutralization of LIF significantly reduced secretion to 0.50 +/- 0.10 ng/well per 3 h. Medium, conditioned by exposure to CRH-target-depleted cultures of anterior pituitary cells, increased net ACTH secretion (from 0.29 +/- 0.03 to 6.54 +/- 0.71 ng/well per 3 h), when added as a challenge to naive, cultured anterior pituitary cells. Inclusion of antiserum to LIF significantly attenuated (5.29 +/- 0.62 ng/well per 3 h) this response. The presence in and secretion of LIF by normal individual pituitary cells was detected using immunocytochemical methods. Seven to 8% of all cells stained positively for LIF, with 66 +/- 11% of those secreting detectable amounts of LIF under unstimulated conditions. LIF colocalized with TSH and LH in pituitary cells. Taken together, these data suggest that LIF can stimulate ACTH secretion by normal anterior pituitary cells, and potentially plays a role as an intrapituitary stimulator of ACTH secretion under certain conditions.
在正常的垂体前叶中，细胞间相互作用对于包括促肾上腺皮质激素（ACTH）在内的激素表达很重要。白血病抑制因子（LIF）由垂体前叶细胞分泌，并刺激AtT20细胞中基础及促肾上腺皮质激素释放激素（CRH）刺激的ACTH分泌。为了确定LIF对正常垂体细胞的影响，我们测量了LIF和抗LIF免疫中和抗血清对培养的绵羊垂体前叶细胞ACTH分泌的影响。在完整的垂体前叶细胞群体中，LIF（10 nM）刺激ACTH分泌（每3小时从0.30±0.06增加到0.77±0.01 ng/孔），而单独的LIF抗血清没有作用（每3小时0.29±0.05 ng/孔）。形成鲜明对比的是，在用药物消除CRH靶细胞后（一种已知可解除对ACTH分泌抑制的情况），基础ACTH分泌升高（每3小时0.74±0.13 ng/孔）；LIF没有进一步刺激作用（每3小时0.73±0.22 ng/孔），但LIF的免疫中和显著降低分泌至每3小时0.50±0.10 ng/孔。用暴露于CRH靶细胞耗竭的垂体前叶细胞培养物条件化的培养基，当作为刺激物添加到未处理的培养垂体前叶细胞中时，增加了ACTH的净分泌（每3小时从0.29±0.03增加到6.54±0.71 ng/孔）。加入LIF抗血清显著减弱了这种反应（每3小时5.29±0.62 ng/孔）。使用免疫细胞化学方法检测了正常单个垂体细胞中LIF的存在和分泌情况。所有细胞中有7%至8%对LIF呈阳性染色，其中66±11%在未刺激条件下分泌可检测量的LIF。LIF在垂体细胞中与促甲状腺激素（TSH）和促黄体生成素（LH）共定位。综上所述，这些数据表明LIF可以刺激正常垂体前叶细胞分泌ACTH，并可能在某些条件下作为垂体内部ACTH分泌的刺激物发挥作用。
