Department of Legal Medicine, Osaka City University Medical School, Osaka, Japan.
Forensic Autopsy Section, Medico-legal Consultation and Postmortem Investigation Support Center, c/o Department of Legal Medicine, Osaka City University Medical School, Osaka, Japan.
Hum Exp Toxicol. 2019 Nov;38(11):1244-1253. doi: 10.1177/0960327119864139. Epub 2019 Jul 18.
Prolactin (PRL) levels can usually be controlled by PRL-inhibiting psychiatric drugs that include anti-dopamine agents. However, the use of dopamine (DA) antagonists may lead to hyperprolactinemia under certain clinical conditions. The aim of this study was to investigate postmortem PRL levels as potential markers of drug abuse, especially that of DA antagonists, in autopsy cases. We examined 121 autopsy cases, excluding cases involving acute hypoxia/ischemia, such as asphyxia, because PRL concentrations are reportedly increased under acute hypoxic conditions. Detected drugs were classified as either DA antagonists, stimulants, psychotropic drugs other than DA antagonists, or other non-psychotropic drugs, and many cases had no detected drugs. Samples comprised blood collected from the right heart chamber and cerebrospinal fluid (CSF). PRL protein level was measured by chemiluminescent immunoassay, and gene expression in the anterior pituitary of autopsy cases was analyzed by reverse transcription-polymerase chain reaction. The PRL-positive cell ratio in the anterior pituitary gland was also measured by immunohistochemical analysis. The results indicated that PRL levels in the serum and CSF were higher in DA antagonist cases than in other cases. PRL levels in the serum and CSF also correlated with the PRL gene expression in cases with abuse of DA antagonists. However, no significant difference in the PRL-positive cell ratio in the anterior pituitary gland was evident between any of the classes of drug-detected and drug-undetected cases. These results suggest that postmortem measurements of PRL transcription levels may be useful for diagnosing cases of DA antagonist use.
催乳素 (PRL) 水平通常可以通过包括抗多巴胺药物在内的抑制 PRL 的精神科药物来控制。然而,在某些临床情况下,使用多巴胺 (DA) 拮抗剂可能会导致高催乳素血症。本研究旨在调查死后催乳素水平是否可作为药物滥用的潜在标志物,尤其是 DA 拮抗剂的滥用。我们检查了 121 例尸检病例,排除了涉及急性缺氧/缺血的病例,如窒息,因为据报道在急性缺氧条件下催乳素浓度会升高。检测到的药物分为 DA 拮抗剂、兴奋剂、除 DA 拮抗剂以外的精神药物或其他非精神药物,许多病例未检测到药物。样本包括从右心腔和脑脊液 (CSF) 采集的血液。通过化学发光免疫分析测量 PRL 蛋白水平,并通过逆转录聚合酶链反应分析尸检病例的前垂体基因表达。还通过免疫组织化学分析测量前垂体催乳素阳性细胞的比例。结果表明,DA 拮抗剂病例的血清和 CSF 中的 PRL 水平高于其他病例。DA 拮抗剂滥用病例的血清和 CSF 中的 PRL 水平也与 PRL 基因表达相关。然而,在任何药物检测和未检测病例之间,前垂体催乳素阳性细胞的比例没有明显差异。这些结果表明,死后 PRL 转录水平的测量可能有助于诊断 DA 拮抗剂使用病例。