Miller G M, Alexander J M, Bikkal H A, Katznelson L, Zervas N T, Klibanski A
Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
J Clin Endocrinol Metab. 1995 Apr;80(4):1386-92. doi: 10.1210/jcem.80.4.7714115.
Somatostatin (SRIF) exerts its diverse biological effects through a family of membrane receptors. In addition to inhibiting GH secretion, SRIF has antiproliferative effects and has been used clinically in the treatment of pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in pituitary adenomas, and it is unknown whether differential expression of SSTR subtypes predicts clinical responses to SRIF analogs. We therefore determined which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma phenotypes and in normal human pituitary tissue using reverse transcriptase-polymerase chain reaction and tested whether expression of specific SSTR subtype mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA was detected in only one somatotroph adenoma as well as in control insulinoma tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To determine whether specific SSTR subtype mRNA expression is required for SRIF inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7) mol/L SRIF in vitro, and significant inhibition of GH release occurred in all adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5 mRNA, which has not been reported in other human endocrine tumor types, is expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5 mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are responsive to SRIF in vitro. Further understanding of SSTR gene expression in pituitary adenomas will facilitate our understanding of the pathogenetic mechanisms of tumorigenesis and may provide a rationale for the use of specific SRIF analogs for clinical application.
生长抑素（SRIF）通过一族膜受体发挥其多样的生物学效应。除了抑制生长激素（GH）分泌外，SRIF还具有抗增殖作用，并已在临床上用于治疗垂体肿瘤。最近在垂体腺瘤中发现了生长抑素受体（SSTR）的表达，而SSTR亚型的差异表达是否能预测对SRIF类似物的临床反应尚不清楚。因此，我们使用逆转录聚合酶链反应确定了哪些SSTR亚型信使核糖核酸（mRNA）在垂体腺瘤表型和正常人体垂体组织中表达，并测试了特定SSTR亚型mRNA的表达对于SRIF在体外抑制人生长激素腺瘤中GH分泌是否必要。在所有类型的垂体腺瘤和正常垂体组织中均鉴定出SSTR亚型1、2和5的mRNA表达。相比之下，仅在一例生长激素腺瘤以及对照胰岛素瘤组织（已知表达SSTR3 mRNA的组织）中检测到SSTR3 mRNA，而在正常垂体组织中未检测到。在任何人体垂体组织中均未检测到SSTR4 mRNA。为了确定SRIF抑制GH分泌是否需要特定SSTR亚型mRNA的表达，对五例生长激素腺瘤进行了体外10⁻⁷mol/L SRIF处理，所有腺瘤中GH释放均受到显著抑制。所有五个肿瘤均表达SSTR2 mRNA和SSTR5 mRNA，三个表达SSTR1 mRNA。SSTR1 mRNA表达的缺失并不影响SRIF抑制GH分泌的能力。我们得出以下结论：1）人垂体腺瘤和正常垂体表达多种SSTR基因转录本；2）SSTR5 mRNA在肿瘤性和正常垂体组织中表达，而在其他人类内分泌肿瘤类型中尚未见报道；3）SSTR2 mRNA、SSTR5 mRNA以及可变的SSTR1 mRNA在分泌GH的肿瘤中表达，这些肿瘤在体外对SRIF有反应。对垂体腺瘤中SSTR基因表达的进一步了解将有助于我们理解肿瘤发生的致病机制，并可能为特定SRIF类似物的临床应用提供理论依据。
