Moritz K, Butkus A, Hantzis V, Peers A, Wintour E M, Dodic M
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville 3052, Victoria, Australia.
Endocrinology. 2002 Apr;143(4):1159-65. doi: 10.1210/endo.143.4.8747.
Low-dose dexamethasone (D) treatment is used in pregnancies where the fetus is suspected to be at risk of congenital/virilizing adrenal hyperplasia. To study if this treatment had any immediate or long-term effects in normal fetuses, pregnant ewes were treated with D (20 microg/kg maternal body weight x d) or saline (S), from d 25-45 of gestation. Tissue was collected from fetuses killed at 45 d (S = 6; D = 8), 130 d (S = 8; D = 8), or lambs at 2 months of age (S = 6; D = 6) and mRNA levels measured using real-time PCR. D treatment reduced adrenal wt at 45 d (S, 12.2 +/- 0.7 mg; D, 6.3 +/- 0.4 mg) and significantly decreased adrenal mRNA for P(450scc). At 130 d, fetuses from the D treatment were growth retarded (S, 3.2 +/- 0.1 kg; D, 2.5 +/- 0.1 g), but the adrenals were appropriate for the body weight. mRNA levels of angiotensinogen, the AT(1) receptor and mineralocorticoid receptor (MR) and GR were similar in kidney and brain (hypothalamus, hippocampus, medulla oblongata) except for hippocampal expression of MR and GR, which was significantly decreased by D treatment. By 2 months, BW and hippocampal MR and GR mRNA levels were similar, and lambs were normotensive (S, 83 +/- 3 mm Hg; D, 78 +/- 3 mm Hg). Thus, there were no persistent, long-term effects of prolonged low-dose D treatment in normal ovine fetuses.
低剂量地塞米松(D)治疗用于怀疑胎儿有先天性/男性化肾上腺增生风险的妊娠。为了研究这种治疗对正常胎儿是否有任何即时或长期影响,在妊娠第25至45天,对怀孕母羊给予D(20微克/千克母体体重×天)或生理盐水(S)。在妊娠45天(S组=6只;D组=8只)、130天(S组=8只;D组=8只)处死胎儿收集组织,或在2月龄时收集羔羊组织(S组=6只;D组=6只),并使用实时PCR测量mRNA水平。D治疗使45天时肾上腺重量降低(S组,12.2±0.7毫克;D组,6.3±0.4毫克),并显著降低P(450scc)的肾上腺mRNA水平。在130天时,接受D治疗的胎儿生长受限(S组,3.2±0.1千克;D组,2.5±0.1克),但其肾上腺与体重相称。除海马体中MR和GR的表达外,肾和脑(下丘脑、海马体、延髓)中血管紧张素原、AT(1)受体、盐皮质激素受体(MR)和糖皮质激素受体(GR)的mRNA水平相似,D治疗使海马体中MR和GR的表达显著降低。到2月龄时,体重和海马体中MR和GR的mRNA水平相似,羔羊血压正常(S组,83±3毫米汞柱;D组,78±3毫米汞柱)。因此,延长的低剂量D治疗对正常绵羊胎儿没有持续的长期影响。