Prolactin and dopamine: what is the connection? A review article.
Prolactin and dopamine: what is the connection? A review article.
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DOI：
10.1177/0269216307087148
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发表时间：
2008-03-01
期刊：
影响因子：
--
通讯作者：
Dinan, Timothy G
中科院分区：
文献类型：
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作者：
Fitzgerald, Peter;Dinan, Timothy G
多巴胺（DA）在调节催乳素（PRL）分泌中起主导作用。通过直接作用于垂体前叶乳营养因子，DA抑制细胞的碱性高分泌张力。它通过与乳营养菌细胞膜上表达的D2受体结合来实现这一目标，D2受体的激活通过多种细胞内信号传导机制导致PRL胞吐和基因表达的减少。下丘脑多巴胺能神经元为脑垂体前叶提供DA，其自身通过“短回路反馈机制”受到PRL反馈的调节。多种其他催乳素分泌调节剂在下丘脑水平通过多巴胺能张力的去抑制（如血清素、GABA、雌激素和阿片类物质）或通过增强多巴胺能张力（如P物质）起作用。所有典型的抗精神病药物都与持续的高催乳素血症有关，因为它们对D2受体具有高亲和力，并且一旦结合就与受体分离缓慢，但非典型药物在导致长时间高催乳素水平的倾向方面差异很大。在那些与催乳素升高相关的非典型症状中，主要的致病因素似乎是母体药物或其活性代谢物（如利培酮、9-羟基利培酮和氨硫pride）的外周到中枢多巴胺受体效价较高。抗精神病药物很容易穿过血脑屏障，一旦与多巴胺受体结合，就会迅速分离，不会导致持续的高泌乳素血症。
Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms. The hypothalamic dopaminergic neurons, which provide DA to the anterior pituitary gland, are themselves regulated by feedback from PRL through a 'short-loop feedback mechanism'. A variety of other modulators of prolactin secretion act at the hypothalamic level by either disinhibition of the dopaminergic tone (e.g. serotonin, GABA, oestrogens and opioids) or by reinforcing it (e.g. substance P). All typical antipsychotic medications are associated with sustained hyperprolactinaemia due to their high affinity for the D2 receptor and their slow dissociation from the receptor once bound, but atypicals differ quite dramatically in their propensity to cause prolonged high prolactin levels. Of those atypicals that are associated with prolactin elevation, the main causative factor appears to be a higher peripheral-to-central dopamine receptor potency of either the parent drug or its active metabolite (e.g. risperidone, 9-hydroxy-risperidone and amisulpride). Antipsychotics that easily cross the blood-brain barrier and exhibit fast dissociation from the dopamine receptor once bound do not result in sustained hyperprolactinaemia.