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人绒毛膜促性腺激素、雄激素、促肾上腺皮质激素、地塞米松及高催乳素血症对血浆性类固醇结合蛋白的影响

Effects of human chorionic gonadotropin, androgens, adrenocorticotropin hormone, dexamethasone and hyperprolactinemia on plasma sex steroid-binding protein.

作者信息

Forest M G, Lecoq A, David M, Pugeat M

机构信息

INSERM U.34, Hôpital Debrousse, Lyon, France.

出版信息

Ann N Y Acad Sci. 1988;538:214-34. doi: 10.1111/j.1749-6632.1988.tb48867.x.

Abstract

This presentation reports the effects of androgens, glucocorticoids and some pituitary hormones on plasma sex steroid-binding protein (SBP). The latter was measured by a solid phase method after desteroidation of the plasma. An hCG test (1500 I.U. every other day X 7) was given to 60 boys. In the children with a normal testosterone (T) rise, plasma SBP decreased (% of basal values) either significantly (38.3 +/- 9.3%, group A; n = 29), or moderately (13.4 +/- 4.4%, group B; n = 9) or did not change (-1.6 +/- 6.4%, group C; n = 10). In the 3 infants tested at an age when SBP normally rise sharply, hCG partially prevented this rise. The administration of either fluoxymesterone (10 mg/m2 for 10 days) or depot-T (4 I.M. injections of 100 mg/m2 every 2 weeks) induced a significant drop (about 2-fold) in plasma SBP in a control group of infants or children, but did not change SBP in 3 infants with the androgen insensitivity syndrome. A single injection of 0.25 mg of ACTH did not significantly alter SBP levels. In contrast, at the end of a 3-day ACTH test (0.5 mg/m2 12 hourly X 6) SBP levels had significantly decreased (mean 35% fall) with no age or sex differences, and with no correlation with the cortisol levels reached. However, the lowering effect of ACTH on SBP levels is likely mediated by glucocorticoids, since its effect was reproduced by high doses (8 mg/day for 3 days) of dexamethasone given at once or after 3 days of treatment at lower dose (20 micrograms/kg BW). It would appear that the depressive effect of ACTH and/or dexamethasone is observed for a threshold dose of glucocorticoids (greater than 5-fold physiological levels) and a certain time (greater than or equal to 3 days) of exposure. The mechanism by which androgens and glucocorticoids lower SBP levels in vivo is not yet understood. From recent experiments, showing that both stimulate the secretion of SBP in hepatoma cells in vitro, it would appear that both hormones may alter SBP metabolism. In a selected population of hyperprolactinemic women, with normal weight and no hirsutism, plasma SBP levels were found in the normal female range. The discrepancy with previous studies in the literature may be explained by differences in the degree of hyperprolactinemia and/or associated hyperandrogenim. This study further documents the multifactorial and intricated hormonal influences involved in the regulation of plasma SBP in vivo.

摘要

本报告阐述了雄激素、糖皮质激素及某些垂体激素对血浆性类固醇结合蛋白(SBP)的影响。血浆经去类固醇化处理后,采用固相法测定SBP。对60名男孩进行了人绒毛膜促性腺激素(hCG)试验(每隔一天注射1500国际单位,共7次)。在睾酮(T)正常升高的儿童中,血浆SBP降低(相对于基础值的百分比),其中显著降低的有(38.3±9.3%,A组;n = 29),中度降低的有(13.4±4.4%,B组;n = 9),未发生变化的有(-1.6±6.4%,C组;n = 10)。在3名处于SBP通常会急剧升高年龄阶段的婴儿中进行测试,hCG部分抑制了这种升高。在一组婴儿或儿童对照组中,给予氟甲睾酮(10 mg/m²,持续10天)或长效睾酮(每2周肌肉注射4次,每次100 mg/m²)均导致血浆SBP显著下降(约2倍),但在3名患有雄激素不敏感综合征的婴儿中,SBP未发生变化。单次注射0.25 mg促肾上腺皮质激素(ACTH)并未显著改变SBP水平。相反,在为期3天的ACTH试验结束时(每12小时注射0.5 mg/m²,共6次),SBP水平显著下降(平均下降35%),且无年龄或性别差异,与所达到的皮质醇水平也无相关性。然而,ACTH对SBP水平的降低作用可能是由糖皮质激素介导的,因为高剂量(8 mg/天,共3天)的地塞米松一次性给药或在较低剂量(20 μg/kg体重)治疗3天后给药,均可重现其作用。似乎对于糖皮质激素的阈值剂量(大于生理水平的5倍)和一定的暴露时间(大于或等于3天),可观察到ACTH和/或地塞米松的抑制作用。雄激素和糖皮质激素在体内降低SBP水平的机制尚不清楚。近期实验表明,二者均可在体外刺激肝癌细胞分泌SBP,因此这两种激素可能都会改变SBP的代谢。在一群体重正常且无多毛症的高催乳素血症女性中,血浆SBP水平处于正常女性范围内。与文献中先前的研究结果存在差异,可能是由于高催乳素血症的程度和/或相关的高雄激素血症不同所致。本研究进一步证明了体内血浆SBP调节涉及多种因素且错综复杂的激素影响。

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