Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Urol Oncol. 2012 Sep;30(5):596-601. doi: 10.1016/j.urolonc.2010.11.001. Epub 2011 Apr 1.
Luteinizing hormone (LH) during androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone analogues (GnRHa) has been thought to be biologically inactive, and the regulation of LH during ADT with GnRHa is thus unknown. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and differentiation, and IGF-1 production in the liver is dependent on growth hormone (GH) secretion from the anterior pituitary. Despite the presence of IGF-1 receptors in the gonadotroph, associations between the GH/IGF-1 and pituitary-gonadal axes, e.g., whether IGF-1 elicits the LH secretion, remain unclear.
Seventy-one patients with localized prostate cancer, who received ADT with GnRHa, were prospectively studied based on their blood samples before treatment and after ADT for 6 months. We employed highly sensitive assays for measurement of serum testosterone (electrochemiluminescence immunoassay), GH/IGF-1 (radioimmunoassay), adrenocorticotropic hormone (ACTH: immunoradiometric assay), LH (chemiluminescent immunoassay), and dehydroepiandrosterone sulfate (DHEA-S: chemiluminescent enzyme immunoassay).
No correlation was noted between the pretreatment LH and IGF-1 levels; after ADT, the serum LH level was closely correlated with the IGF-1 concentration [Spearman's correlation coefficient (rs) = 0.370, P = 0.001]. The serum levels of androgens and gonadotropins reduced following ADT (P < 0.001 in all). The serum IGF-1 level increased (22 ± 6 nmol/L) compared with that at the baseline (19 ± 5 nmol/L) (P < 0.001), but no change was observed in the serum GH concentration between before and after ADT (1.4 ± 2.3 vs. 0.9 ± 0.9 μg/L, respectively, P = 0.691). The serum testosterone level was not correlated with the LH level either before or after ADT. The testosterone and DHEA-S levels after ADT were correlated with ACTH concentration (rs = 0.367, P = 0.002 and rs = 0.354, P = 0.002, respectively). We did not identify any correlations between the serum IGF-1 concentration and Gleason score, PSA value, or androgen levels.
During ADT with GnRHa, IGF-1 possibly promotes LH production, although its role is unclear. Associations among pituitary-gonadal, pituitary-adrenal, and GH/IGF-1 axes represented by IGF-1-mediated LH secretion and ACTH-mediated androgen synthesis are of interest, since both prostate epithelium proliferation and male anabolic activity are involved in these 3 axes. Assessment of oncologic outcomes is warranted for their significance in patients with prostate cancer.
促性腺激素释放激素类似物（GnRHa）去势治疗期间的黄体生成素（LH）被认为是生物活性的，因此 GnRHa 去势治疗期间 LH 的调节尚不清楚。胰岛素样生长因子-1（IGF-1）参与细胞增殖和分化的调节，肝脏中 IGF-1 的产生依赖于垂体前叶分泌的生长激素（GH）。尽管在促性腺激素细胞中存在 IGF-1 受体，但 GH/IGF-1 和垂体性腺轴之间的关联，例如 IGF-1 是否引发 LH 分泌，仍不清楚。
71 例局部前列腺癌患者接受 GnRHa 去势治疗，根据治疗前和去势治疗 6 个月后的血液样本进行前瞻性研究。我们采用高度敏感的检测方法测量血清睾酮（电化学发光免疫测定法）、GH/IGF-1（放射免疫测定法）、促肾上腺皮质激素（ACTH：免疫放射测定法）、LH（化学发光免疫测定法）和硫酸脱氢表雄酮（DHEA-S：化学发光酶免疫分析法）。
预处理 LH 和 IGF-1 水平之间无相关性；去势治疗后，血清 LH 水平与 IGF-1 浓度密切相关[Spearman 相关系数（rs）=0.370，P=0.001]。去势治疗后血清雄激素和促性腺激素水平降低（所有 P<0.001）。与基线相比，血清 IGF-1 水平升高（22±6nmol/L）（P<0.001），但去势治疗前后血清 GH 浓度无变化（分别为 1.4±2.3 和 0.9±0.9μg/L，P=0.691）。去势治疗前后，血清睾酮水平与 LH 水平也无相关性。去势治疗后，睾酮和 DHEA-S 水平与 ACTH 浓度相关（rs=0.367，P=0.002 和 rs=0.354，P=0.002）。我们没有发现血清 IGF-1 浓度与 Gleason 评分、PSA 值或雄激素水平之间存在任何相关性。
在 GnRHa 去势治疗期间，IGF-1 可能促进 LH 的产生，但其作用尚不清楚。通过 IGF-1 介导的 LH 分泌和 ACTH 介导的雄激素合成代表的垂体性腺、垂体肾上腺和 GH/IGF-1 轴之间的关联很有趣，因为前列腺上皮细胞增殖和男性合成代谢活性都涉及这 3 个轴。评估这些关联对前列腺癌患者的意义是必要的。
