progesterone receptor mRNA upregulation in a rat model of hepatic
Respiratory alkalosis from hyperventilation is seen frequently in patients with hepatic cirrhosis. Although the etiology is unknown, we previously demonstrated that estradiol and progesterone concentrations correlated with a decreased PaCO2 in cirrhotic patients, suggesting that hormonal changes might stimulate respiratory centers in the brain. The present study explores the possibility that hormonal changes induced by end stage liver disease mediate hyperventilation through the upregulation of brainstem progesterone receptors. Sprague-Dawley rats received CCL4 to induce cirrhosis; control animals were given mineral oil. PaCO2, serum estradiol, and progesterone levels were measured. Cirrhosis was documented by liver biopsy. RT-PCR was used to determine progesterone receptor mRNA expression. CCL4 treatment resulted in decreased serum progesterone (2.5 ng/mL vs 18.8, P=0.002) and increased estradiol (57.8 ± 8.47 pg/mL vs 31.9 ± 6.96, P < 0.001). CCL4 treated animals had significantly increased brainstem progesterone receptor expression ratios (0.1502 ± 0.0637 vs 0.0853 ± 0.0348, P=0.04). There was no statistically significant decrease in PaCO2 among cirrhotic rats (35.3 vs 39.2, P=0.18). This is the first study to show estradiol induced upregulation of progesterone receptors in the brainstem of cirrhotic animals. Further study is needed to determine if this upregulation is responsible for the hyperventilation common in cirrhotic patients.
Keywords: Carbon tetrachloride, estradiol, respiratory alkalosis, cirrhosis, progesterone
Cardiopulmonary Pathophysiology 9: 33-39, 2000
L. Abt, M.D.
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