Effect of early glucocorticoid treatment on MR and GR in late gestation ovine kidney

被引:19
作者
Hantzis, V
Albiston, A
Matsacos, D
Wintour, EM
Peers, A
Koukoulas, I
Myles, K
Moritz, K
Dodic, M [1 ]
机构
[1] Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Melbourne, Vic 3010, Australia
[2] Baker Med Res Inst, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
cortisol; dexamethasone; glucocorticoid receptor; mineralocorticoid receptor; ontogeny; sheep; development;
D O I
10.1046/j.1523-1755.2002.00157.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. The ontogeny of the renal mineralocorticoid (MR) and glucocorticoid (GR) receptors in the ovine fetus, and the effects of early exposure to synthetic or natural gluco-corticoids on the expression of these genes in late gestation were examined. Methods. A partial cDNA sequence for the ovine MR was cloned and used to generate primers and probes to measure MR mRNA expression by real-time polymerase chain reaction (PCR). GR mRNA was also measured. Kidneys were collected from ovine fetuses at various stages of gestation (days 60 to 140), twin ovine fetuses at 130 days, from ewes treated at days 26 to 28 with either saline, dexamethasone or cortisol, and adult sheep. Ligand binding was used to determine both GR and MR protein levels in all 130-day-old fetuses and adults. Results. No significant changes in the expression of either renal MR or GR were detected throughout gestation. Cytosolic protein levels were higher in the fetal kidneys than in the adult. There was a significant increase in both fetal MR and GR mRNA expression, but not protein levels in kidneys from ewes pretreated with dexamethasone. Conclusions. MR and GR mRNA are expressed throughout development in ovine fetal kidneys. Dexamethasone treatment resulted in increased expression of MR and GR mRNA but not protein levels. The dissociation between fetal mRNA and protein levels, relative to adult kidneys, suggests that it may be confounding to draw conclusions based on mRNA levels alone.
引用
收藏
页码:405 / 413
页数:9
相关论文
共 41 条
[31]   Differential effects of pregnancy on mineralocorticoid and glucocorticoid receptor availability and immunoreactivity in cortisol feedback sites [J].
Roesch, DM ;
Keller-Wood, M .
NEUROENDOCRINOLOGY, 1999, 70 (01) :55-62
[32]   Developmental changes and molecular weight of immunoreactive glucocorticoid receptor protein in the ovine fetal hypothalamus and pituitary [J].
Saoud, CJ ;
Wood, CE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 229 (03) :916-921
[33]   GESTATIONAL CHANGES IN RENAL RESPONSIVENESS TO CORTISOL IN THE OVINE FETUS [J].
TOWSTOLESS, MK ;
MCDOUGALL, JG ;
WINTOUR, EM .
PEDIATRIC RESEARCH, 1989, 26 (01) :6-10
[34]   Glucocorticoid receptor β:: View I [J].
Vottero, A ;
Chrousos, GP .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 1999, 10 (08) :333-338
[35]  
Webster JC, 1997, J BIOL CHEM, V272, P9287
[36]  
Wintour E, 1998, PRINCIPLES PERINATAL, P511
[37]   PLACENTAL-TRANSFER OF ALDOSTERONE IN THE SHEEP [J].
WINTOUR, EM ;
COGHLAN, JP ;
HARDY, KJ ;
LINGWOOD, BE ;
RAYNER, M ;
SCOGGINS, BA .
JOURNAL OF ENDOCRINOLOGY, 1980, 86 (02) :305-310
[38]   Fetal origins of adult hypertension: a renal mechanism? [J].
Woods, LL .
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2000, 9 (04) :419-425
[39]   CHANGES IN GLUCOCORTICOID RECEPTOR NUMBER IN THE HYPOTHALAMUS AND PITUITARY OF THE SHEEP FETUS WITH GESTATIONAL-AGE AND AFTER ADRENOCORTICOTROPIN TREATMENT [J].
YANG, K ;
JONES, SA ;
CHALLIS, JRG .
ENDOCRINOLOGY, 1990, 126 (01) :11-17
[40]   Tissue-specific expression of alpha and beta messenger ribonucleic acid isoforms of the human mineralocorticoid receptor in normal and pathological states [J].
Zennaro, MC ;
Farman, N ;
Bonvalet, JP ;
Lombes, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (05) :1345-1352