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Estrogen is nephroprotective in the rat remnant kidney in a rat model of intrauterine growth restriction
Author(s) -
Grigore Daniela,
Ojeda Norma B.,
Alexander Barbara T.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.941.6
Subject(s) - endocrinology , medicine , intrauterine growth restriction , estrogen , kidney , offspring , blood pressure , fetus , biology , pregnancy , genetics
Recent epidemiological studies suggest that an enhanced susceptibility to renal injury may originate in fetal life. Our laboratory utilizes a model of placental insufficiency in the rat to induce intrauterine growth restriction (IUGR) and hypertension in IUGR offspring. Pre‐pubertal female IUGR are hypertensive; however, blood pressure (BP) returns to normotensive values after puberty. Ovariectomy (OVX) leads to a significant increase in BP (plus 17 mmHg) in IUGR with no effect in control suggesting estradiol may contribute to BP regulation in female IUGR. We hypothesized that susceptibility to renal injury may be enhanced by IUGR, an effect exacerbated by OVX. Despite the increase in BP by ovariectomy, IUGR did not manifest renal injury as determined by expression of TGFβ1, a cytokine key to the progression of renal disease; mRNA expression measured by Real‐Time PCR. Exposure to a secondary insult, reduction of renal mass (RRM), also did not lead to renal injury in intact control or IUGR. However, RRM did elicit a marked 4‐fold increase in remnant kidney TGFβ1 mRNA expression in OVX IUGR with no effect in OVX control. At the protein level, TGFβ1 was also significantly increased by RRM in OVX IUGR compared to OVX control (507 pgTGFβ1/ml vs. 344 pgTGFβ1/ml). Thus, renal TGFβ1 was enhanced in response to RRM in OVX IUGR, suggesting that estradiol plays a protective role against the development of renal injury in a model of IUGR.