Mashiter K, De Marco L, Van Noorden S, Adams E, Loizou M, Joplin G F, Peters T J
Metabolism. 1982 Sep;31(9):931-6. doi: 10.1016/0026-0495(82)90184-6.
A patient with galactorrhea, amenorrhae and severe acromegaly was found to have a large pituitary adenoma. In view of the severity of the disease the serum growth hormone (GH) level (22.5 mlU/liter) was considered inappropriately low. Tissue from the adenoma was obtained during successful treatment with interstitial irradiation. (90Yttrium). Trypsin-dispersed biopsy cells in culture for 12 days secreted low amounts of GH compared to the same number of adenoma cells from 5 other unselected acromegalics or a normal pituitary. No other hormones were secreted in culture. Immunocytochemical staining was positive only with GH antisera but showed low intracellular content. This was confirmed by direct analysis of the tumor tissue which showed the GH content to be only 20% of that found in 5 normal pituitaries and 4% of that found in 8 other adenomas from acromegalics. Electron microscopy showed a striking appearance, with GH secretory granules that were sparse in number, smaller than usual, and in the main arranged around numerous intracellular profiles with double membranes and low electron density that were tentatively identified as autophagic vacuoles (secondary lysosomes). Subcellular fractionation showed the distribution of the radioimmunoassayable GH in the gradient to be coincident with the peak of the lysosomes whereas in 2 other acromegalics the GH peak was clearly separated from the lysosomes. We conclude that the simultaneous appearance in our patient of the relatively low serum GH together with a large tumor and severe acromegaly can be explained biochemically by the striking finding of crinophagy - disposal of hormone secretory granules within the somatotroph cells themselves.
一名患有溢乳、闭经和严重肢端肥大症的患者被发现患有巨大垂体腺瘤。鉴于病情严重程度，血清生长激素（GH）水平（22.5 mIU/升）被认为过低。在成功进行间质内照射（钇-90）治疗期间获取了腺瘤组织。与来自其他5例未经挑选的肢端肥大症患者的相同数量腺瘤细胞或正常垂体相比，培养12天的经胰蛋白酶分散的活检细胞分泌的GH量较低。培养过程中未分泌其他激素。免疫细胞化学染色仅对GH抗血清呈阳性，但细胞内含量较低。对肿瘤组织的直接分析证实了这一点，结果显示GH含量仅为5例正常垂体中所发现含量的20%，以及8例其他肢端肥大症患者腺瘤中所发现含量的4%。电子显微镜检查显示出一种显著的外观，GH分泌颗粒数量稀少、比通常的小，并且主要围绕着许多具有双膜且电子密度低的细胞内结构排列，这些结构初步被确定为自噬泡（次级溶酶体）。亚细胞分级分离显示，梯度中可通过放射免疫测定的GH分布与溶酶体峰一致，而在另外2例肢端肥大症患者中，GH峰与溶酶体明显分离。我们得出结论，在我们的患者中，血清GH相对较低与巨大肿瘤和严重肢端肥大症同时出现，从生化角度可以通过显著的自噬现象来解释，即生长激素分泌细胞自身内激素分泌颗粒的处置。
