Miller G M, Alexander J M, Klibanski A
Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
J Clin Endocrinol Metab. 1996 Jan;81(1):80-3. doi: 10.1210/jcem.81.1.8550798.
Gonadotroph tumors predominantly secrete FSH or free gonadotropin hormone subunits and rarely LH. In contrast to normal gonadotrophs, a subset of tumors synthesize FSH beta-subunit (SU) in excess of alpha-SU, and the cause of gonadotropin hormone-SU biosynthetic defects in these tumors is unknown. Gonadotropin-releasing hormone (GnRH) is known to modify gonadotropin hormone-SU biosynthesis and secretion and may be an important determinant of gonadotroph tumor hormone regulation. Data in experimental animals have demonstrated that endogenous expression of GnRH may occur in the pituitary. We therefore determined whether 1) the GnRH gene is expressed in gonadotroph tumors and normal pituitaries using reverse transcriptase (RT)-PCR; 2) the GnRH receptor gene is co-expressed in gonadotroph tumors; 3) an alternative upstream transcriptional start site on the GnRH gene is utilized; and 4) media from primary cultures of gonadotroph tumors have detectable GnRH immunoreactivity by RIA. GnRH messenger RNA (mRNA) was detected in 10/10 gonadotroph tumors, eight of which expressed GnRH-Receptor mRNA. Both mRNAs were detected in all normal pituitaries studied (n = 6). Six of 10 gonadotroph tumors and 3/6 normal pituitaries had GnRH transcripts derived from the upstream transcriptional start site (5'GnRH). GnRH immunoreactivity was detected in overnight media from 3/3 primary gonadotroph tumor cultures (range: 1.89-5.86pg/mL; limit of detection (LD) = < 1.58pg/mL) but was not detectable in control media. This is the first study to demonstrate endogenous GnRH gene expression in human pituitary adenomas and normal human pituitary tissue. The presence of both GnRH and GnRH-Rc suggest that GnRH may be a paracrine/autocrine regulator of cell function in the pituitary and may affect gonadotroph tumor hormone phenotype.
促性腺激素瘤主要分泌促卵泡生成素（FSH）或游离促性腺激素亚基，很少分泌促黄体生成素（LH）。与正常促性腺激素细胞相比，一部分肿瘤合成的FSHβ亚基（SU）超过α-SU，而这些肿瘤中促性腺激素-SU生物合成缺陷的原因尚不清楚。已知促性腺激素释放激素（GnRH）可改变促性腺激素-SU的生物合成和分泌，可能是促性腺激素瘤激素调节的重要决定因素。实验动物的数据表明，GnRH的内源性表达可能发生在垂体中。因此，我们确定：1）使用逆转录酶（RT）-PCR检测GnRH基因在促性腺激素瘤和正常垂体中是否表达；2）GnRH受体基因在促性腺激素瘤中是否共表达；3）GnRH基因是否利用了一个替代的上游转录起始位点；4）促性腺激素瘤原代培养物的培养基通过放射免疫分析（RIA）是否具有可检测到的GnRH免疫反应性。在10个促性腺激素瘤中有10个检测到GnRH信使核糖核酸（mRNA），其中8个表达GnRH受体mRNA。在所研究的所有正常垂体（n = 6）中均检测到这两种mRNA。10个促性腺激素瘤中有6个和6个正常垂体中有3个具有源自上游转录起始位点（5'GnRH）的GnRH转录本。在3个促性腺激素瘤原代培养物的过夜培养基中检测到GnRH免疫反应性（范围：1.89 - 5.86pg/mL；检测限（LD）= < 1.58pg/mL），但在对照培养基中未检测到。这是首次证明人垂体腺瘤和正常人垂体组织中存在内源性GnRH基因表达的研究。GnRH和GnRH-Rc的存在表明，GnRH可能是垂体细胞功能的旁分泌/自分泌调节因子，可能影响促性腺激素瘤的激素表型。
