Madersbacher S, Untergasser G, Gerth R, Hermann M, Schwärzler P, Dirnhofer S, Berger P
Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck.
Exp Clin Endocrinol Diabetes. 1998;106(1):61-7. doi: 10.1055/s-0029-1211952.
The recent demonstration of ectopic production of human placental lactogen (PL) in the human testis and ovary prompted us to reassess its role under non-pregnant physiological and pathological conditions. Possible physiological hPL concentrations and potential age-related changes in the sera of healthy young and elderly individuals (n = 75) selected according to the SENIEUR-protocol were investigated by a highly sensitive (detection limit: 2 pg/ml) and specific (cross-reactivity with prolactin and human growth hormone (hGH) of less than 0.001% and 0.0001%, respectively) monoclonal antibody-based time-resolved fluoroimmunoassay (IFMA) established in our laboratory. All individuals, even the aged probands (mean age: 72 +/- 3a), had hPL-levels below 20 pg/ml, in contrast to glycoprotein hormones, such as luteinizing hormone or human chorionic gonadotropin (hCG). To determine the significance of hPL as a tumour marker, serum samples of 12 testicular cancer patients with highly elevated levels of holo-hCG (mean: 42.490 ng/ml) at diagnosis were followed over 6-12 months and analysed with the hPL-IFMA. Elevation of hPL was seen in 10 patients, but the respective levels were 2-3 orders of magnitude smaller than those of holo-hCG and returned earlier to undetectable values. These in vivo data were compared to the hPL secretion pattern of the choriocarcinoma cell lines JAR and BeWo in vitro. In tissue culture supernatants of the two cell lines hPL was detected only in JAR cells, whereas both cell lines secreted holo-hCG. In conclusion, the fact that hPL is not physiologically present in peripheral blood but is produced ectopically in the human testis and ovary suggest auto/paracrine functions of this molecule. The significance of hPL as a tumour marker for patients with testicular cancer is limited as it provides no additional information to holo-hCG.
近期在人类睾丸和卵巢中发现人胎盘催乳素(PL)的异位产生,这促使我们重新评估其在非妊娠生理和病理条件下的作用。我们采用在本实验室建立的高灵敏度(检测限:2 pg/ml)和特异性(与催乳素和人生长激素(hGH)的交叉反应率分别小于0.001%和0.0001%)的基于单克隆抗体的时间分辨荧光免疫测定法(IFMA),对根据SENIEUR方案选取的健康青年和老年个体(n = 75)血清中可能的生理性hPL浓度以及潜在的年龄相关变化进行了研究。所有个体,甚至是老年受试者(平均年龄:72±3岁),其hPL水平均低于20 pg/ml,这与促黄体生成素或人绒毛膜促性腺激素(hCG)等糖蛋白激素不同。为了确定hPL作为肿瘤标志物的意义,对12例诊断时全hCG水平高度升高(平均:42,490 ng/ml)的睾丸癌患者的血清样本进行了6至12个月的随访,并采用hPL-IFMA进行分析。10例患者出现hPL升高,但相应水平比全hCG低2至3个数量级,且更早恢复到不可检测值。将这些体内数据与体外绒癌细胞系JAR和BeWo的hPL分泌模式进行了比较。在这两种细胞系的组织培养上清液中,仅在JAR细胞中检测到hPL,而两种细胞系均分泌全hCG。总之,hPL在外周血中并非生理性存在,而是在人类睾丸和卵巢中异位产生,这表明该分子具有自分泌/旁分泌功能。hPL作为睾丸癌患者肿瘤标志物的意义有限,因为它并未为全hCG提供额外信息。