Hofland Leo J, van der Hoek Joost, van Koetsveld Peter M, de Herder Wouter W, Waaijers Marlijn, Sprij-Mooij Diana, Bruns Christian, Weckbecker Gisbert, Feelders Richard, van der Lely Aart-Jan, Beckers Albert, Lamberts Steven W J
Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2004 Apr;89(4):1577-85. doi: 10.1210/jc.2003-031344.
To determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenomas. OCT (10 nM) significantly inhibited GH release in seven of nine GH-secreting pituitary adenoma cultures (range, -26 to -73%), SOM230 (10 nM) in eight of nine cultures (range, -22 to -68%), and SRIF-14 (10 nM) in six of six cultures (range, -30 to -75%). The sst analysis showed predominant but variable levels of somatostatin receptor (sst)(2) and sst(5) mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH release in a dose-dependent manner with an IC(50) value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH release inhibition (IC(50), 0.5 nM), compared with OCT (IC(50), 0.02 nM) and SRIF-14 (IC(50), 0.02 nM). A positive correlation was found between sst(2) but not sst(5) mRNA levels in the adenoma cells and the inhibitory potency of OCT on GH release in vivo and in vitro, and the effects of SOM230 and SRIF-14 in vitro. In three prolactinoma cultures, 10 nM OCT weakly inhibited prolactin (PRL) release in only one (-28%), whereas 10 nM SOM230 significantly inhibited PRL release in three of three cultures (-23, -51, and -64.0%). The inhibition of PRL release by SOM230 was related to the expression level of sst(5) but not sst(2) mRNA. Several conclusions were reached. First, SOM230 has a broad profile of inhibition of tumoral pituitary hormone release in the low nanomolar range, probably mediated via both sst(2) and sst(5) receptors. The higher number of responders of GH-secreting pituitary adenoma cultures to SOM230, compared with OCT, suggest that SOM230 has the potency to increase the number of acromegalic patients which can be biochemically controlled. Second, compared with OCT, SOM230 is more potent in inhibiting PRL release by mixed GH/PRL-secreting adenoma and prolactinoma cells.
为了确定具有广泛生长抑素（SRIF）受体结合能力的新型生长抑素（SRIF）类似物SOM230的抑制谱，我们比较了SOM230、奥曲肽（OCT）和SRIF - 14对不同类型分泌性垂体腺瘤培养物激素释放的体外作用。OCT（10 nM）在9种生长激素分泌性垂体腺瘤培养物中的7种中显著抑制生长激素（GH）释放（范围为 - 26%至 - 73%），SOM230（10 nM）在9种培养物中的8种中（范围为 - 22%至 - 68%），SRIF - 14（10 nM）在6种培养物中的6种中（范围为 - 30%至 - 75%）。生长抑素受体（sst）分析显示生长抑素受体（sst）(2)和sst(5) mRNA表达水平占主导但存在差异。在一种对OCT完全耐药的培养物中，SOM230和SRIF - 14以剂量依赖方式显著抑制GH释放，IC(50)值在低纳摩尔范围内。在其他培养物中，与OCT（IC(50)，0.02 nM）和SRIF - 14（IC(50)，0.02 nM）相比，SOM230对GH释放的抑制效力较低（IC(50)，0.5 nM）。在腺瘤细胞中，sst(2)而非sst(5) mRNA水平与OCT在体内和体外对GH释放的抑制效力以及SOM230和SRIF - 14在体外的作用之间存在正相关。在3种催乳素瘤培养物中，10 nM OCT仅在1种培养物中微弱抑制催乳素（PRL）释放（ - 28%），而10 nM SOM230在3种培养物中的3种中显著抑制PRL释放（ - 23%、 - 51%和 - 64.0%）。SOM230对PRL释放的抑制与sst(5)而非sst(2) mRNA的表达水平相关。得出了几个结论。首先，SOM230在低纳摩尔范围内对垂体肿瘤激素释放具有广泛的抑制谱，可能通过sst(2)和sst(5)受体介导。与OCT相比，生长激素分泌性垂体腺瘤培养物对SOM230有反应者数量更多，这表明SOM230有能力增加可通过生化方式控制的肢端肥大症患者数量。其次，与OCT相比，SOM230在抑制混合性生长激素/催乳素分泌腺瘤和催乳素瘤细胞释放PRL方面更有效。
