Asa S L, Kovacs K, Horvath E, Singer W, Smyth H S
Department of Pathology, St. Michael's Hospital, Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 1992 Jul;75(1):68-75. doi: 10.1210/jcem.75.1.1352308.
Pituitary tumors producing GH and PRL are morphologically classified as monomorphous bihormonal acidophil stem cell adenomas (ASCAs) which cause hyperprolactinemia and two tumor types which are usually associated with acromegaly, the monomorphous plurihormonal mammosomatotroph adenomas (MSAs) and bimorphous mixed somatotroph-lactotroph adenomas. We studied 12 MSAs, 2 ASCAs, and 10 mixed adenomas in vitro to assess the secretory behavior of these tumors diagnosed by immunohistochemistry and electron microscopy. GH release by MSAs and all but one mixed tumor was greater than that of PRL; the opposite was true of the ASCAs. One mixed tumor which caused impotence and hyperprolactinemia contained predominantly lactotrophs and released greater amounts of PRL than of GH in vitro. All 12 MSAs and 6 of 10 mixed tumors released alpha-subunit of glycoprotein hormones. Incubation with GHRH increased release of GH and PRL by all tumors and of alpha-subunit when present; the responses of all hormones were parallel among MSAs whereas among mixed adenomas, GH and alpha-subunit had greater responses than PRL. TRH stimulated GH, PRL, and alpha-subunit release by MSAs in parallel; among mixed adenomas, PRL response was generally greater than that of GH or alpha-subunit. SRIH markedly reduced GH release by all MSAs; it inhibited GH and alpha-subunit release by mixed tumors more than it affected PRL. Bromocriptine inhibited GH, PRL, and alpha-subunit release by most MSAs and mixed tumors but did not inhibit GH or PRL release by ASCAs. This study demonstrates release of GH, PRL, and alpha-subunit by these morphologically classified plurihormonal tumors in vitro. Variable quantities of GH and PRL released by the different tumor types correlate with immunohistochemical and clinical data. The dynamic studies indicate that regulation of GH, PRL, and alpha-subunit release can be affected by GHRH, TRH, SRIH, and bromocriptine in these adenomas and suggest differences in receptor status. Our data strengthen the view that these three plurihormonal adenomas of the acidophil cell line are not only morphologically but also functionally different and warrant separation.
分泌生长激素（GH）和催乳素（PRL）的垂体瘤在形态学上被分类为单形双激素嗜酸干细胞腺瘤（ASCA），其可导致高催乳素血症，还有两种通常与肢端肥大症相关的肿瘤类型，即单形多激素乳腺生长激素细胞腺瘤（MSA）和双形混合生长激素 - 催乳激素细胞腺瘤。我们对12例MSA、2例ASCA和10例混合腺瘤进行了体外研究，以评估这些经免疫组织化学和电子显微镜诊断的肿瘤的分泌行为。MSA和除1例混合瘤外的所有混合瘤释放的GH均多于PRL；ASCA则相反。1例导致阳痿和高催乳素血症的混合瘤主要由催乳激素细胞组成，体外释放的PRL量多于GH。所有12例MSA和10例混合瘤中的6例释放糖蛋白激素的α亚基。与生长激素释放激素（GHRH）一起孵育可增加所有肿瘤释放的GH和PRL，以及存在时α亚基的释放；在MSA中，所有激素的反应是平行的，而在混合腺瘤中，GH和α亚基的反应比PRL更大。促甲状腺激素释放激素（TRH）平行刺激MSA释放GH、PRL和α亚基；在混合腺瘤中，PRL的反应通常大于GH或α亚基。生长抑素（SRIH）显著降低所有MSA释放的GH；它对混合瘤释放GH和α亚基的抑制作用比对PRL的影响更大。溴隐亭抑制大多数MSA和混合瘤释放GH、PRL和α亚基，但不抑制ASCA释放GH或PRL。本研究证明了这些形态学分类的多激素肿瘤在体外释放GH、PRL和α亚基。不同肿瘤类型释放的不同量的GH和PRL与免疫组织化学和临床数据相关。动态研究表明，在这些腺瘤中，GHRH、TRH、SRIH和溴隐亭可影响GH、PRL和α亚基的释放调节，并提示受体状态存在差异。我们的数据强化了这样一种观点，即嗜酸细胞系的这三种多激素腺瘤不仅在形态学上不同，而且在功能上也不同，需要进行区分。
