Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

George B. Richerson


Purpose: To determine if the deficiency in the hypercapnic ventilatory response as a result of 70% loss of serotonergic neurons in male Pet-1 knockout mice and the sparing of the female Pet-1 knockout mice can been accounted for and corrected by supplementation with estrogen and progesterone. Methods: Using whole-body flow-through plethysmography, 5 male Pet-1 -/- mice and 5 wild type mice were exposed to room air, 3%, 5%, 7%, and 10% CO2 and VE measured. All mice were then treated with oral 17β-estradiol (2500 nM) for 48 hours followed by a SC injection of progesterone (2 mg/kg). One hour after injection all plethysmography studies were repeated. Results: Before treatment Pet-1 knockout mice showed a trend towards decreased VE at room air, 3%, and 7% CO2, with statistical significance at 5% CO2 (p <0.05), and an identical VE only at 10% CO2. Absolute changes in VE after treatment were insignificant; the differences in VE between genotypes achieved significance at control, 3%, and 5% CO2 (p <0.05) while now VE at 7% and 10% CO2 exposures were identical (p < 0.05). Conclusion: The partial recovery of the male Pet-1 knockout phenotype provides evidence that the remaining serotonergic neurons can recover some chemoreceptor function under the influence of female sex hormones, which in turn may partially explain the female Pet-1 knockout phenotype.