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J Am Soc Nephrol 14:3102-3110, 2003
© 2003 American Society of Nephrology

BASIC SCIENCE

Decreases in Renal Functional Reserve and Proximal Tubular Fluid Output in Conscious Oophorectomized Rats: Normalization with Sex Hormone Substitution

Camilla Birch Nielsen*,{dagger}, Allan Flyvbjerg{dagger}, Jens Meldgaard Bruun{ddagger}, Axel Forman§, Lise Wogensen|| and Klaus Thomsen*

*Department of Biological Psychiatry, Institute for Basic Psychiatric Research, {dagger}Medical Research Laboratories, Institute of Experimental Clinical Research, {ddagger}Department of Endocrinology and Metabolism, §Department of Gynecology, and ||Research Laboratory for Biochemical Pathology, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark.

Correspondence to Dr. Klaus Thomsen, Department of Biological Psychiatry, Institute for Basic Psychiatric Research, Skovagervej 2, DK-8240 Risskov, Denmark. Phone: +45-7789-3512; Fax: +45-7789-3549; E-mail: klt{at}psykiatri.aaa.dk

ABSTRACT. Age-dependent glomerulosclerosis with reduced GFR develops earlier among men than among women. Therefore, whether female sex hormones could prevent the age-dependent decrease in GFR was investigated. The kidney function in oophorectomized rats treated with placebo (OOX group), estrogen (OOX+E2 group), or estrogen plus progesterone (OOX+E2+P group) for 5 mo and in sham-operated rats (sham group) was examined. The rats were 13 mo of age at the time of the investigation. They were conscious and chronically instrumented. The results demonstrated that estrogen, alone or in combination with progesterone, was without effect on the baseline GFR and effective renal plasma flow but prevented severe decreases in the renal functional reserve and fractional proximal tubular fluid output (lithium clearance technique, fractional lithium excretion), which were observed in the OOX group. The renal functional reserve (estimated by stimulation with glycine) was -223 ± 151, 483 ± 129, 675 ± 76, and 208 ± 140 µl/min in the OOX, OOX+E2, OOX+E2+P, and sham groups, respectively. Fractional lithium excretion was 12.4 ± 3.1, 26.8 ± 2.0, 31.8 ± 2.5, and 23.6 ± 3.3% in the OOX, OOX+E2, OOX+E2+P, and sham groups, respectively. In conclusion, oophorectomy at the age of 8 mo did not produce a decrease in baseline GFR in female rats within a period of 5 mo. However, oophorectomy led to severe decreases in the renal functional reserve and fractional proximal tubular fluid output. Both effects were prevented with administration of estrogen. Sham-operated rats demonstrated values for renal functional reserve and fractional lithium excretion that were between those observed for the OOX group and the groups treated with sex hormones.




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