Knepel W, Schwaninger M, Wesemeyer G, Döhler K D, Sandow J
Endocrinology. 1987 Feb;120(2):732-8. doi: 10.1210/endo-120-2-732.
The effect of GH-releasing hormone (GHRH) on the release of the endogenous opioid dynorphin from rat adenohypophysis was investigated in vitro. Rat anterior pituitary quarters were incubated in vitro, and hormone release into the incubation medium was measured by RIAs. Human pancreatic GHRH [hpGHRH-(1-44)] as well as human Leu27,Gly45-GHRH [GHRH-(1-45)] enhanced the secretion of dynorphin A1-13-like immunoreactivity (Dyn A1-13-IR) in a concentration-dependent manner. The concentrations of hpGHRH-(1-44) that stimulated the release of Dyn A1-13-IR were about 100-fold higher than those that enhanced GH secretion. GH release induced by hpGHRH-(1-44) was blocked by somatostatin (IC50, approximately 10 nM) without affecting hpGHRH-(1-44)-induced release of Dyn A1-13-IR. GH release was elicited by prostaglandin E2, while Dyn A1-13-IR secretion remained unchanged. At concentrations that enhanced Dyn A1-13-IR release, hpGHRH-(1-44) also elicited LH and FSH secretion. The LHRH antagonist D-pGlu1, D-Phe2,D-Trp3,6-LHRH blocked the secretion of Dyn A1-13-IR, LH, and FSH induced by hpGHRH-(1-44), whereas the LHRH antagonist did not influence the simultaneous GH release elicited by hpGHRH-(1-44). A possible direct effect of GHRH on the LHRH receptor was examined in radioligand binding studies using iodinated D-Ala6, des-Gly10-LHRH ethylamide (LHRH-A). The binding of [125I]iodo-LHRH-A to rat anterior pituitary membranes was completely displaced by hpGHRH-(1-44) and GHRH-(1-45). The deduced apparent dissociation constants were about 3 orders of magnitude higher than that of LHRH-A, but were close to those concentrations that enhanced Dyn A1-13-IR release. We conclude that GHRH-induced release of Dyn A1-13-IR is unrelated to GH release. High concentrations of GHRH may interact directly with LHRH receptors on gonadotrophs and thereby enhance the release of LH, FSH, and Dyn A1-13-IR.
在体外研究了生长激素释放激素（GHRH）对大鼠腺垂体中内源性阿片肽强啡肽释放的影响。将大鼠垂体前叶切成小块进行体外培养，通过放射免疫分析法测定培养液中激素的释放量。人胰腺GHRH [hpGHRH-(1-44)] 以及人Leu27,Gly45-GHRH [GHRH-(1-45)] 以浓度依赖的方式增强了强啡肽A1-13样免疫反应性（Dyn A1-13-IR）的分泌。刺激Dyn A1-13-IR释放的hpGHRH-(1-44)浓度比增强生长激素（GH）分泌的浓度高约100倍。生长抑素可阻断hpGHRH-(1-44)诱导的GH释放（IC50约为10 nM），但不影响hpGHRH-(l-44)诱导的Dyn A1-13-IR释放。前列腺素E2可引起GH释放，而Dyn A1-13-IR分泌保持不变。在能增强Dyn A1-13-IR释放的浓度下，hpGHRH-(1-44)也可引起促黄体生成素（LH）和促卵泡生成素（FSH）的分泌。促性腺激素释放激素（LHRH）拮抗剂D-pGlu1,D-Phe2,D-Trp3,6-LHRH可阻断hpGHRH-(1-44)诱导的Dyn A1-13-IR、LH和FSH分泌，而该LHRH拮抗剂不影响hpGHRH-(1-44)同时引起的GH释放。在使用碘化D-Ala6,去-Gly10-LHRH乙酰胺（LHRH-A）的放射性配体结合研究中，检测了GHRH对LHRH受体的可能直接作用。hpGHRH-(1-44)和GHRH-(1-45)可完全取代[125I]碘-LHRH-A与大鼠垂体前叶膜的结合。推导的表观解离常数比LHRH-A高约3个数量级，但接近增强Dyn A1-13-IR释放的浓度。我们得出结论，GHRH诱导的Dyn A1-13-IR释放与GH释放无关。高浓度的GHRH可能直接与促性腺细胞上的LHRH受体相互作用，从而增强LH、FSH和Dyn A1-13-IR的释放。
