Houben H, Denef C
Laboratory of Cell Pharmacology, University of Leuven School of Medicine, Belgium.
Endocrinology. 1990 May;126(5):2257-66. doi: 10.1210/endo-126-5-2257.
The effect of the bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin-C (NMC), and the ranatensin-like peptides, neuromedin-B (NMB), neuromedin-B30 (NMB30), and neuromedin-B32 (NMB32), on pituitary GH and PRL release was studied in perifused anterior pituitary aggregate cell cultures from 9- to 12-week-old male rats cultured in serum-free defined medium supplemented with 0.05 nM T3 and 4 nM dexamethasone (DEX). All peptides stimulated PRL and GH release. GRP and NMC stimulated hormone release in a concentration-dependent manner between 0.1-10 nM. NMB was slightly more potent than NMB30 and NMB32, but was significantly less potent than GRP and NMC. The magnitude of the PRL response to GRP and NMC inversely correlated with that of the GH response. Cultures with relatively low PRL response levels displayed high GH responses, whereas the opposite was found in cultures with high PRL response levels. The stimulatory actions of GRP, NMC, and NMB were blocked by the bombesin receptor antagonist Leu13 psi (CH2NH) Leu14-bombesin, supporting the specificity of the findings. Addition of 1 nM estradiol (E2) to the culture medium provoked an impressive (4- to 10-fold) increase in the magnitude of the GH response to NMC without changing the EC50 value (0.5 nM). In contrast, E2 significantly decreased the stimulation of GH release by rat GH-releasing factor. In the E2-treated aggregates 3 nM NMC stimulated GH release to a comparable extent as 0.1 nM GRF. 5 alpha-Dihydrotesterone (10 and 100 nM) and DEX (80 nM) also enhanced the GH response to NMC, but to a much smaller extent than E2. E2 had also a stimulatory effect on the PRL response to NMC, particularly in cultures with a low intrinsic PRL response. The PRL response to NMC was decreased by DEX and slightly augmented by 5 alpha-dihydrotestosterone. It is concluded that bombesin- and ranatensin-like peptides have a stimulatory effect on GH and PRL release at the pituitary level. Since their action on GH release is strongly potentiated by E2 and much less so by glucocorticoids, these peptides clearly distinguish their activity and specificity from that of the protagonist releasing factor GH-releasing factor, suggesting a role in sex-related differences in GH release or in the control of GH secretion during sexual maturation.
在添加了0.05 nM三碘甲状腺原氨酸（T3）和4 nM地塞米松（DEX）的无血清限定培养基中培养的9至12周龄雄性大鼠的前脑垂体聚集细胞培养物中，研究了蛙皮素样肽、胃泌素释放肽（GRP）和神经介素C（NMC），以及蛙皮素样肽、神经介素B（NMB）、神经介素B30（NMB30）和神经介素B32（NMB32）对垂体生长激素（GH）和催乳素（PRL）释放的影响。所有肽均刺激PRL和GH释放。GRP和NMC在0.1至10 nM之间以浓度依赖性方式刺激激素释放。NMB的效力略高于NMB30和NMB32，但明显低于GRP和NMC。PRL对GRP和NMC的反应幅度与GH反应幅度呈负相关。PRL反应水平相对较低的培养物显示出高GH反应，而在PRL反应水平高的培养物中则相反。GRP、NMC和NMB的刺激作用被蛙皮素受体拮抗剂Leu13 psi（CH2NH）Leu14-蛙皮素阻断，支持了研究结果的特异性。向培养基中添加1 nM雌二醇（E2）可使GH对NMC的反应幅度显著增加（4至10倍），而不改变半数有效浓度（EC50值，0.5 nM）。相反，E2显著降低了大鼠生长激素释放因子对GH释放的刺激作用。在经E2处理的聚集体中，3 nM NMC刺激GH释放的程度与0.1 nM生长激素释放因子（GRF）相当。5α-二氢睾酮（10和100 nM）和DEX（80 nM）也增强了GH对NMC的反应，但程度远小于E2。E2对PRL对NMC的反应也有刺激作用，特别是在固有PRL反应较低的培养物中。DEX降低了PRL对NMC的反应，而5α-二氢睾酮则使其略有增强。结论是，蛙皮素样肽和蛙皮素样肽在垂体水平对GH和PRL释放有刺激作用。由于它们对GH释放的作用被E2强烈增强，而被糖皮质激素增强的程度要小得多，这些肽明显区别于主要释放因子生长激素释放因子的活性和特异性，提示它们在GH释放的性别相关差异或性成熟期间GH分泌的控制中起作用。
