Brainstem progesterone receptor mRNA upregulation in a rat model of hepatic cirrhosis

Respiratory alkalosis from hyperventilation is seen frequently in patients with hepatic cirrhosis. Although the etiology is unknown, we previously dem onstrated that estradiol and progesterone concentrations correlated with a decreased PaCO2 in cirrhotic patients, suggesting that hormonal changes mig ht stimulate respiratory centers in the brain. The present study explores t he possibility that hormonal changes induced by end stage liver disease med iate hyperventilation through the upregulation of brainstem progesterone re ceptors. Sprague-Dawley rats received CCL4 to induce cirrhosis; control ani mals were given mineral oil. PaCO2, serum estradiol, and progesterone level s 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 express ion ratios (0.1502 +/- 0.0637 vs 0.0853 +/- 0.0348, P=0.04). There was no s tatistically 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 s tudy is needed to determine if this upregulation is responsible for the hyp erventilation common in cirrhotic patients.