Lawton N F, Evans A J, Weller R O
J Neurol Sci. 1981 Feb;49(2):229-39. doi: 10.1016/0022-510x(81)90081-2.
An in vitro technique for continuous perifusion of human pituitary has been developed to study the effect of dopamine on hormone release. Pituitary tissue was obtained from 2 patients with prolactinomas, 3 patients with acromegaly and 2 patients with disseminated malignancy whose pituitaries were normal. During perifusion prolactin release was reversibly inhibited from both normal and adenomatous glands, confirming the direct effect of dopamine on the pituitary. Rebound secretion following inhibition suggested that dopamine acted upon hormone release rather than synthesis under these conditions. Growth hormone (GH) release in vivo is stimulated by levodopa in normal subjects but inhibited in acromegaly. In vitro, however, we have demonstrated inhibition of GH release by dopamine, regardless of whether the pituitary was normal or adenomatous. This finding does not support the view that dopamine receptors are acquired by tumour cells as a result of adenomatous dedifferentiation. It is suggested that the paradoxical GH response to levodopa in acromegaly can be explained by a dual action of dopamine at hypothalamic and pituitary levels. According to this hypothesis GH release is stimulated by a hypothalamic effect, whereas inhibition occurs at pituitary level. The net effect of these opposing stimuli in vivo may depend upon the sensitivity of dopamine receptors at the prevailing concentration of GH.
已开发出一种用于人垂体连续灌流的体外技术,以研究多巴胺对激素释放的影响。垂体组织取自2例催乳素瘤患者、3例肢端肥大症患者和2例垂体正常的播散性恶性肿瘤患者。在灌流过程中,正常腺体和腺瘤性腺体的催乳素释放均受到可逆性抑制,证实了多巴胺对垂体的直接作用。抑制后的反弹分泌表明,在这些条件下多巴胺作用于激素释放而非合成。左旋多巴在正常受试者体内刺激生长激素(GH)释放,但在肢端肥大症患者中则抑制GH释放。然而,在体外,我们已证明多巴胺抑制GH释放,无论垂体是正常的还是腺瘤性的。这一发现不支持肿瘤细胞因腺瘤去分化而获得多巴胺受体的观点。有人提出,肢端肥大症患者对左旋多巴的GH反应矛盾可通过多巴胺在下丘脑和垂体水平的双重作用来解释。根据这一假说,GH释放受下丘脑效应刺激,而抑制发生在垂体水平。这些相反刺激在体内的净效应可能取决于多巴胺受体在当时GH浓度下的敏感性。