Atkin S L, Landolt A M, Jeffreys R V, Diver M, Radcliffe J, White M C
University Department of Medicine and Chemical Pathology, Liverpool University, United Kingdom.
J Clin Endocrinol Metab. 1993 Sep;77(3):831-7. doi: 10.1210/jcem.77.3.8370706.
The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro.
研究了人重组碱性成纤维细胞生长因子（bFGF）对26例分别单独分泌催乳素（PRL）（6例肿瘤）、PRL和生长激素（GH）（18例肿瘤）或单独分泌GH（2例肿瘤）的人垂体前叶腺瘤的分泌和/或增殖的影响。分泌研究在4小时、4天和21天进行，增殖研究在4天进行。在10例肿瘤中检测了bFGF在4小时内对分泌的急性影响。与对照组相比，bFGF（10 nmol/L）使2例肿瘤中的PRL增加（126%和290%；P<0.05），在第3例肿瘤中使PRL和GH增加（分别为183%和133%；P<0.05），而7例肿瘤未受影响。对14例肿瘤进行了4天的研究。bFGF（10 nmol/L）使11例同时分泌PRL和GH的肿瘤中的9例（117 - 525%；P<0.05）以及所有3例单独分泌PRL的肿瘤中的PRL分泌增加（156%、183%和691%；P<0.01）。在其中2例同时分泌GH和PRL的肿瘤中，用0.1、1和10 nmol/L的bFGF绘制的剂量反应曲线表明，所有3种浓度均能产生刺激作用。bFGF（10 nmol/L）使11例混合性肿瘤中的2例的GH分泌增加（分别为159%和196%；P<0.05）。在2例进行了3周研究的肿瘤中，5 nmol/L的bFGF逐渐刺激PRL分泌而不影响GH分泌（106%和207%；P<0.05）。在4天后对7例肿瘤进行1小时溴脱氧尿苷掺入后的双重免疫染色来测定组织增殖。在任何肿瘤中标记指数均未超过1.2%，10 nmol/L的bFGF对腺癌细胞的增殖没有影响。这些结果表明，bFGF可能在人垂体腺瘤中PRL分泌的刺激调节中起旁分泌作用，并且这些作用很可能是由于激素合成增加所致。体外细胞培养系统可用于研究增殖潜能。然而，bFGF在体外对分泌PRL以及分泌PRL加GH的人垂体前叶腺瘤没有促有丝分裂作用。
