Stojanovic Marko, Wu Zida, Stiles Craig E, Miljic Dragana, Soldatovic Ivan, Pekic Sandra, Doknic Mirjana, Petakov Milan, Popovic Vera, Strasburger Christian, Korbonits Márta
Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia.
University of Belgrade, Medical Faculty, Belgrade, Serbia.
Endocr Connect. 2019 Apr;8(4):326-337. doi: 10.1530/EC-19-0082.
Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients.
Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP.
Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT.
Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact.
芳烃受体相互作用蛋白（AIP）在进化上保守，在整个生物体中广泛表达。功能丧失的AIP突变易导致青年期垂体腺瘤。AIP在正常和肿瘤性生长激素分泌细胞的分泌小泡中与生长激素共定位。AIP蛋白在循环中可检测到。我们旨在通过研究生长激素缺乏症（GHD）和肢端肥大症患者基线时以及生长激素刺激或抑制后的血清AIP和生长激素水平，来调查AIP和生长激素可能的共同分泌情况。
对GHD患者（n = 13）和年龄-体重指数匹配的正常生长激素轴对照患者（n = 31）进行胰岛素耐量试验（ITT）。对活动性肢端肥大症患者（n = 26）和年龄-体重指数匹配的正常生长激素轴对照患者（n = 18）进行口服葡萄糖耐量试验（OGTT）。开发了用于测量循环AIP的内部免疫测定法。
血清AIP水平在0.1 ng/mL范围内，与性别、年龄或体重指数无关。GHD与非GHD患者之间或肢端肥大症与无肢端肥大症患者之间的基线AIP无差异。OGTT或ITT期间的峰值、谷值或曲线下面积无变化。ITT或OGTT期间血清AIP与生长激素无相关性。
通过一种新型免疫测定法评估了体内人循环血清AIP。AIP水平与年龄、性别或体重指数无关，且不受低血糖或高血糖影响。尽管在分泌小泡中共定位，但AIP和生长激素在基线时或生长激素刺激或抑制试验期间无相关性。建立了可靠的血清AIP测量平台，以进一步研究其循环来源、作用和影响。
