Influence of ovariectomy on catecholamine synthesis in rats exposed to dexamethasone in utero

Previous studies have demonstrated that when pregnant rat dams are administered the synthetic glucocorticoid, dexamethasone (DEX), in late gestation, the female offspring exhibit altered autonomic regulation compared to females exposed to vehicle (Veh). This altered autonomic regulation is characterized by a reduced high frequency power component of heart rate variability and increased stress-responsive blood pressure and heart rate. Moreover, we have recently determined that heart rate in DEX-exposed females shows a greater reliance on sympathetic nervous system at rest and during stress, as compared to Veh-exposed rats. The purpose of the current project was to further investigate the effect of in-utero DEX exposure and gonadal steroid hormones on local autonomic regulation in adult female offspring. Specifically, we measured left ventricular and adrenal expression of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and catechol-o-methyltransferase (COMT) as indicators of sympathetic regulation. Pregnant dams were administered DEX (0.4mg/kg per day) or Veh on gestation days 18-21. At 9 weeks, the female offspring underwent an OVX or Sham surgery. At 12 weeks, these rats were euthanized on diestrus and the left ventricles and adrenals were processed and subjected to western blot analysis to quantify protein expression of interest. TH expression tended to be reduced in left ventricle (0.57-fold, p>0.05) yet increased (1.5-fold, p>0.05) in adrenal gland in rats prenatally exposed to DEX. In both cases, there was no difference in expression of TH between vehicle and DEX rats following OVX. DBH expression was not different in adrenal gland, regardless of prenatal exposure or OVX. However, in the left ventricle, OVX resulted in an overall reduction in DBH expression that reached statistical significance in the DEX OVX rats (-50%, p=0.0079 vs Veh Sham). COMT expression was not influenced by prenatal DEX or OVX in the left ventricle. Taken together, the findings reveal a differential regulation of catecholamine synthesis in adrenal gland as compared to the left ventricle of the heart. The findings suggest that local regulation of catecholamine synthesis does not underlie our previous findings of increased sympathetic nervous system activation of females exposed to DEX in utero. Additional investigation of cardiac beta-adrenergic receptor expression, as well measures of the central autonomic nervous system circuitry, may provide further insight into the sex-dependent impact of DEX and gonadal hormones on local autonomic regulation. NIH U54 MH118919, University of Arizona Clinical Translational Sciences, Maximizing Student Development Graduate Access Fellowship This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.