Desai B J, Monson J P, Holdstock J G, Aylwin S J, Geddes J F, Wood D F, Burrin J M
Department of Clinical Biochemistry, Royal London Hospital, United Kingdom.
J Clin Endocrinol Metab. 1994 Dec;79(6):1771-7. doi: 10.1210/jcem.79.6.7527412.
Hormone release in culture in response to pituitary adenylate cyclase-activating polypeptide (PACAP) was examined in 28 human pituitary adenomas: 10 null cell adenomas, 4 gonadotropin-, 6 GH-, 6 ACTH-, and 2 PRL-producing adenomas. The effects of PACAP38 were compared with those of the classical hypothalamic releasing hormones and other activators of intracellular signaling pathways. PACAP38 significantly stimulated GH release from 1 somatotrope tumor (125 +/- 3% of control; P < 0.05) and ACTH release from 3 corticotrope tumors (134 +/- 6%, 136 +/- 7%, and 137 +/- 9% of control; P < 0.05). The effects of PACAP38 were less potent than either GHRH on GH release in the somatotrope tumor or CRH on ACTH release in the corticotrope tumors but similar to the responses seen with the cAMP analog 8-bromo-cAMP (8-Br-cAMP). No detectable effects of PACAP38 on hormone release from null cell, gonadotropin-, or PRL-producing adenomas were observed. Of the 5 somatotrope tumors that failed to respond to PACAP38, all also failed to respond to either 8-Br-cAMP, TRH, or GHRH. Of the corticotrope tumors that failed to respond, 2 of the 3 also failed to respond to CRH. In addition to eliciting hormone release appropriate to the tumor type, PACAP38 also stimulated glycoprotein hormone alpha-subunit (alpha SU) release from one somatotrope tumor (229 +/- 35% of control, P < 0.01) and one corticotrope tumor (149 +/- 4% of control; P < 0.01). This response was not mimicked by 8-Br-cAMP in the somatotrope tumor, but in the corticotrope tumor a significant alpha SU release was also seen after stimulation with the protein kinase C activator 12-O-tetradecanoyl-phorbol-13-acetate and 8-Br-cAMP. These results suggest that the novel hypothalamic peptide PACAP38 has a modest role in the regulation of GH, ACTH, and alpha SU secretion from some human tumourous pituitary corticotropes and somatotropes. Further studies are needed to elucidate the intracellular signaling pathways that mediate the effects of PACAP on hormone secretion by these tumor types.
在28例人类垂体腺瘤中检测了垂体腺苷酸环化酶激活多肽（PACAP）刺激下的激素释放情况，其中包括10例无功能细胞腺瘤、4例促性腺激素腺瘤、6例生长激素腺瘤、6例促肾上腺皮质激素腺瘤和2例催乳素腺瘤。将PACAP38的作用与经典下丘脑释放激素及细胞内信号通路其他激活剂的作用进行了比较。PACAP38显著刺激了1例生长激素瘤释放生长激素（为对照的125±3%；P<0.05）以及3例促肾上腺皮质激素瘤释放促肾上腺皮质激素（分别为对照的134±6%、136±7%和137±9%；P<0.05）。在生长激素瘤中，PACAP38对生长激素释放的作用不如生长激素释放激素（GHRH），在促肾上腺皮质激素瘤中，其对促肾上腺皮质激素释放的作用不如促肾上腺皮质激素释放激素（CRH），但与环磷酸腺苷（cAMP）类似物8-溴环磷酸腺苷（8-Br-cAMP）的作用相似。未观察到PACAP38对无功能细胞腺瘤、促性腺激素腺瘤或催乳素腺瘤释放激素有可检测到的作用。在5例对PACAP38无反应的生长激素瘤中，所有瘤对8-Br-cAMP、促甲状腺激素释放激素（TRH）或GHRH均无反应。在对PACAP38无反应的促肾上腺皮质激素瘤中，3例中有2例对CRH也无反应。除了引发与肿瘤类型相符的激素释放外，PACAP38还刺激了1例生长激素瘤（为对照的229±35%，P<0.01）和1例促肾上腺皮质激素瘤（为对照的149±4%；P<0.01）释放糖蛋白激素α亚基（αSU）。在生长激素瘤中，8-Br-cAMP未模拟出这种反应，但在促肾上腺皮质激素瘤中，蛋白激酶C激活剂12-O-十四烷酰佛波醇-13-乙酸酯和8-Br-cAMP刺激后也观察到了显著的αSU释放。这些结果表明，新型下丘脑肽PACAP38在调节某些人类肿瘤性垂体促肾上腺皮质激素细胞和生长激素细胞分泌生长激素、促肾上腺皮质激素和αSU方面起适度作用。需要进一步研究以阐明介导PACAP对这些肿瘤类型激素分泌作用的细胞内信号通路。
