Ishibashi M, Yamaji T
J Clin Invest. 1984 Jan;73(1):66-78. doi: 10.1172/JCI111208.
To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)1 and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed. This inhibition was blocked by D2 receptor blockade with metoclopramide or sulpiride, but not by D1 receptor blockade. Similarly, dopamine suppressed GH and PRL release by nonadenomatous pituitary cells in a dose-dependent manner, which was again blocked by D2 receptor blockade. The minimum effective concentration of dopamine required for a significant inhibition of PRL secretion (0.01 microM) was lower than that for GH release (0.1 microM). Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells. This effect was blocked by sulpiride, phentolamine, however, was ineffective. When TRH was added to the media, both GH and PRL secretion were enhanced in adenoma cells, while only the stimulation of PRL release was observed in nonadenomatous pituitary cells. Coincubation of TRH and dopamine resulted in variable effects on GH and PRL secretion. Somatostatin consistently lowered GH and PRL secretion in both adenomatous and nonadenomatous pituitary cells and completely blocked the TRH-induced stimulation of GH and PRL secretion from adenoma cells. Opioid peptides (1 microM) failed to affect hormone release. These results suggest that no qualitative difference in GH and PRL responses to dopaminergic agonists or to somatostatin exists between adenoma cells of acromegalic patients and normal pituitary cells, and that the direct effect of catecholamines on GH and PRL secretion from human pituitary cells is mediated mainly through dopamine receptor activation.
为了确定儿茶酚胺以及包括促甲状腺激素释放激素（TRH）1和生长抑素在内的激素对肢端肥大症患者和正常受试者垂体激素释放的作用机制和作用部位，研究了这些物质对培养的人腺瘤性和非腺瘤性垂体细胞生长激素（GH）和催乳素（PRL）分泌的影响。当向培养基中加入多巴胺（0.01 - 0.1微摩尔）或溴隐亭（0.01 - 0.1微摩尔）时，观察到肢端肥大症患者腺瘤细胞的GH和PRL分泌受到显著抑制。这种抑制作用可被甲氧氯普胺或舒必利阻断D2受体所阻断，但不能被阻断D1受体所阻断。同样，多巴胺以剂量依赖的方式抑制非腺瘤性垂体细胞的GH和PRL释放，这再次被阻断D2受体所阻断。显著抑制PRL分泌所需的多巴胺最小有效浓度（0.01微摩尔）低于抑制GH释放所需的浓度（0.1微摩尔）。去甲肾上腺素同样会抑制腺瘤性和非腺瘤性垂体细胞的PRL分泌。这种作用被舒必利阻断，然而酚妥拉明无效。当向培养基中加入TRH时，腺瘤细胞中的GH和PRL分泌均增强，而在非腺瘤性垂体细胞中仅观察到PRL释放受到刺激。TRH与多巴胺共同孵育对GH和PRL分泌产生不同的影响。生长抑素持续降低腺瘤性和非腺瘤性垂体细胞中的GH和PRL分泌，并完全阻断TRH诱导的腺瘤细胞中GH和PRL分泌的刺激。阿片肽（1微摩尔）未能影响激素释放。这些结果表明，肢端肥大症患者的腺瘤细胞与正常垂体细胞在对多巴胺能激动剂或生长抑素的GH和PRL反应上没有质的差异，并且儿茶酚胺对人垂体细胞GH和PRL分泌的直接作用主要通过多巴胺受体激活介导。
