Nielsen S, Mellemkjaer S, Rasmussen L M, Ledet T, Astrup J, Weeke J, Jørgensen J O
Medical Department M, Aarhus Kommunehospital, Aarhus University Hospital, Aarhus C, Denmark.
J Clin Endocrinol Metab. 1998 Aug;83(8):2997-3000. doi: 10.1210/jcem.83.8.5046.
Growth hormone (GH)-releasing peptides (GHRP) or secretagogs (GHS) constitute a family of synthetic compounds with potent and specific GH releasing activity. The receptor (GHS-R) has recently been cloned even though the endogenous ligand remains to be identified. GHRPs act both at the hypothalamic and the pituitary level through mechanisms involving amplification of GH-releasing hormone activity and functional somatostatin antagonism. In the present study we examined the co-expression of messenger RNA (mRNA) for GHS-R and all 5 somatostatin receptor subtypes (sstr 1-5) in 28 human pituitary tumors by RT-PCR. GHS-R transcription was detected in 11 out of 12 somatotroph adenomas and in 2 out of 2 prolactinomas, whereas GHS-R expression was detected in only 2 out of 14 clinically nonfunctioning adenomas (NFPA), and no expression was seen in the only ACTH secreting adenoma. Almost all tumors expressed sstr 2 mRNA (n = 24), whereas only 1 tumor expressed sstr 4 mRNA. The expression of sstr 3 mRNA was inversely associated with GHS-R expression (P < 0.001), which could be attributed to a high prevalence of sstr 3 expression in NFPA. This study suggests that GHS-R expression is predominantly observed in somatotroph adenomas and much less so in NFPA. Moreover, the presence of a distinct pattern of somatostatin receptor subtype co-expression is suggested, which may provide a molecular basis for the complex interaction between GHRPs and somatostatin.
生长激素(GH)释放肽(GHRP)或促分泌素(GHS)是一类具有强大且特异性GH释放活性的合成化合物家族。尽管内源性配体仍有待确定,但受体(GHS-R)最近已被克隆。GHRP通过涉及放大GH释放激素活性和功能性生长抑素拮抗作用的机制,在下丘脑和垂体水平发挥作用。在本研究中,我们通过逆转录聚合酶链反应(RT-PCR)检测了28例人类垂体肿瘤中GHS-R信使核糖核酸(mRNA)与所有5种生长抑素受体亚型(sstr 1-5)的共表达情况。在12例生长激素细胞腺瘤中的11例以及2例催乳素瘤中的2例中检测到了GHS-R转录,而在14例临床无功能腺瘤(NFPA)中仅2例检测到GHS-R表达,在唯一的促肾上腺皮质激素分泌腺瘤中未检测到表达。几乎所有肿瘤都表达sstr 2 mRNA(n = 24),而只有1例肿瘤表达sstr 4 mRNA。sstr 3 mRNA的表达与GHS-R表达呈负相关(P < 0.001),这可能归因于NFPA中sstr 3表达的高发生率。本研究表明,GHS-R表达主要见于生长激素细胞腺瘤,在NFPA中则少见得多。此外,提示存在生长抑素受体亚型共表达的独特模式,这可能为GHRP与生长抑素之间的复杂相互作用提供分子基础。