Sze Lisa, Tschopp Oliver, Neidert Marian C, Bernays René L, Ghirlanda Claudia, Zwimpfer Cornelia, Wiesli Peter, Schmid Christoph
Division of Endocrinology and Diabetology, Kantonsspital Winterthur, Brauerstrasse 15, CH-8401 Winterthur, Switzerland; Division of Endocrinology and Diabetology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Division of Endocrinology and Diabetology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Growth Horm IGF Res. 2019 Apr;45:20-24. doi: 10.1016/j.ghir.2019.02.002. Epub 2019 Feb 18.
GH excess in acromegaly leads to lower fat mass and insulin resistance; both reverse following pituitary surgery. Soluble delta like-1 homolog (sDlk1) inhibits adipocyte differentiation and may mediate the antiadipogenic effects of GH. It is released into the circulation by ectodomain shedding through 'A Disintegrin And Metalloproteinase domain 17' (ADAM17), which also sheds soluble α-Klotho (sKlotho). Klotho is a transmembrane protein, which influences life span. sKlotho inhibits insulin signalling, and is markedly elevated in acromegaly and decreases after surgery. Therefore, we examined if sDlk1 parallels the course of sKlotho, which could explain the well-known changes in fat mass in patients with acromegaly after surgery.
We measured serum levels of GH, IGF-1, sDlk1 and sKlotho (both by ELISA) in 42 treatment-naïve acromegaly patients (20 females/22 males) before and 1-3 months after transsphenoidal surgery. Data are presented as median(interquartile range).
GH decreased in all patients postoperatively (in 32/42 to <1 ng/ml during oral glucose tolerance testing). Likewise, IGF-1 and sKlotho decreased in all patients, from 587 (432-708) to 195 (133-270) ng/ml, and from 4.0 (2.7-5.9) to 0.7 (0.6-1.2) ng/ml, respectively; sDlk1 fell in 40/42 subjects, from 10.7 (5.8-13.4) to 7.1 (3.7-10.4) ng/ml following pituitary surgery. P < 0.0001 for all parameters.
sDlk1 declined after pituitary surgery in our patients with acromegaly, but to a lesser extent than sKlotho. It remains to be seen whether this may contribute to the well-known postoperative changes in body composition. Our findings may extend beyond the scope of acromegaly, and thus further elucidate mechanisms in the fields of obesity and anti-ageing.
肢端肥大症患者生长激素（GH）分泌过多会导致脂肪量减少和胰岛素抵抗；垂体手术后这些情况会逆转。可溶性δ样1同源物（sDlk1）可抑制脂肪细胞分化，并可能介导GH的抗脂肪生成作用。它通过“解整合素和金属蛋白酶结构域17”（ADAM17）介导的胞外域脱落释放到循环中，ADAM17同时也会使可溶性α-klotho（sKlotho）脱落。Klotho是一种跨膜蛋白，会影响寿命。sKlotho抑制胰岛素信号传导，在肢端肥大症患者中显著升高，术后降低。因此，我们研究了sDlk1是否与sKlotho的变化过程相似，这可以解释肢端肥大症患者术后众所周知的脂肪量变化。
我们在42例未经治疗的肢端肥大症患者（20名女性/22名男性）经蝶窦手术前及术后1 - 3个月测量了血清GH、胰岛素样生长因子-1（IGF-1）、sDlk1和sKlotho的水平（均采用酶联免疫吸附测定法）。数据以中位数（四分位间距）表示。
所有患者术后GH均下降（口服葡萄糖耐量试验期间，32/42例患者降至<1 ng/ml）。同样，所有患者的IGF-1和sKlotho均下降，分别从587（432 - 708）ng/ml降至195（133 - 270）ng/ml，以及从4.0（2.7 - 5.9）ng/ml降至0.7（0.6 - 1.2）ng/ml；垂体手术后，40/42例受试者的sDlk1下降，从10.7（5.8 - 13.4）ng/ml降至7.1（3.7 - 10.4）ng/ml。所有参数的P<0.0001。
在我们的肢端肥大症患者中，垂体手术后sDlk1下降，但幅度小于sKlotho。这是否会导致众所周知的术后身体成分变化还有待观察。我们的发现可能超出肢端肥大症的范围，从而进一步阐明肥胖和抗衰老领域的机制。
