Cooper D S, Ridgway E C, Kliman B, Kjellberg R N, Maloof F
J Clin Invest. 1979 Dec;64(6):1669-80. doi: 10.1172/JCI109629.
Metabolic clearance rates (MCR) and production rates (PR) of prolactin (PRL) have been determined by the constant infusion to equilibrium technique in 11 normal subjects, 6 patients with hyperthyroidism, 4 patients with hypothyroidism, and 9 patients with hyperprolactinemia. PRL MCR was also determined tin four patients during dopamine infusion. Mean PRL MCR was 46 +/- 1 ml/min per m2 in women and 44 +/- 3 ml/min per m2 in men, and was significantly correlated with body mass (r = 0.84, P less than 0.001). In contrast with controls, PRL MCR was higher in hyperthyroidism (MCR = 52 +/- 8 ml/min per m2, P less than 0.05), was slightly lower in hypothyroidism (MCR = 38 +/- 10 ml/min per m2, P = NS), and was significantly correlated with serum thyroxine (r = 0.46, P less than 0.02). PRL MCR was lower than controls in hyperprolactinemia (MCR = 40 +/- 5 ml/min per m2, P less than 0.01) and was inversely correlated with serum PRL (r = -0.72, P less than 0.001). PRL MCR was not significantly changed by dopamine infusion. Mean PRL PR for women and men was 211 +/- 74 and 187 +/- 44 micrograms/d per m2, respectively (P = NS). In hyperthyroidism the PRL PR was elevated (PR = 335 +/- 68 micrograms/d per m2, P less than 0.02), but in hypothyroidism the increase (PR = 233 +/- 159 micrograms/d per m2) was not significant. In hyperprolactinemia the PRL PR was extremely high (PR = 31,000 +/- 29,000 micrograms/d per m2). Dopamine infusion decreased RPL PR from 270 to 66 micrograms/d per m2 indicating that its effect was on pituitary PRL secretion and not PRL metabolism. To evaluate possible circulating PRL heterogeneity that might arise during infusion, gel filtration of infusate and serum obtained during the MCR procedure was performed. Labeled monomeric PRL (peak III, Kav (partition coefficient) = 0.4) was partially converted to two larger forms (peaks I and II) in vivo. Peak I (Kav = 0) was 30--40% immunoprecipitable, although peak II (Kav = 0.2) was not immunoprecipitable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of peak I resulted in greater than or equal to 90% conversion to peak III and restoration of full immunoactivity. Thus, peak I is a noncovalently linked aggregate that is partially immunoactive, and therefore able to alter MCR determinations. These studies demonstrate the impact of hormone heterogeneity on MCR estimations and suggest that gel filtration of immunoprecipitable material be an integral part of future MCR measurements.
采用持续输注至平衡技术，测定了11名正常受试者、6名甲状腺功能亢进患者、4名甲状腺功能减退患者和9名高泌乳素血症患者的泌乳素（PRL）代谢清除率（MCR）和分泌率（PR）。还对4名患者在多巴胺输注期间测定了PRL MCR。女性的平均PRL MCR为46±1 ml/min per m2，男性为44±3 ml/min per m2，且与体重显著相关（r = 0.84，P＜0.001）。与对照组相比，甲状腺功能亢进患者的PRL MCR较高（MCR = 52±8 ml/min per m2，P＜0.05），甲状腺功能减退患者的PRL MCR略低（MCR = 38±10 ml/min per m2，P =无显著性差异），且与血清甲状腺素显著相关（r = 0.46，P＜0.02）。高泌乳素血症患者的PRL MCR低于对照组（MCR = 40±5 ml/min per m2，P＜0.01），且与血清PRL呈负相关（r = -0.72，P＜0.001）。多巴胺输注对PRL MCR无显著影响。女性和男性的平均PRL PR分别为211±74和187±44 μg/d per m2（P =无显著性差异）。甲状腺功能亢进时PRL PR升高（PR = 335±68 μg/d per m2，P＜0.02），但甲状腺功能减退时升高（PR = 233±159 μg/d per m2）不显著。高泌乳素血症时PRL PR极高（PR = 31,000±29,000 μg/d per m2）。多巴胺输注使RPL PR从270降至66 μg/d per m2，表明其作用于垂体PRL分泌而非PRL代谢。为评估输注期间可能出现的循环PRL异质性，对MCR测定过程中获得的输注液和血清进行了凝胶过滤。标记的单体PRL（峰III，分配系数Kav = 0.4）在体内部分转化为两种较大形式（峰I和峰II）。峰I（Kav = 0）30 - 40%可被免疫沉淀，而峰II（Kav = 0.2）不可被免疫沉淀。峰I的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳导致≥90%转化为峰III并恢复完全免疫活性。因此，峰I是一种部分具有免疫活性的非共价连接聚集体，能够改变MCR测定结果。这些研究证明了激素异质性对MCR估计的影响，并表明对可免疫沉淀物质进行凝胶过滤应成为未来MCR测量的一个组成部分。
