Professor and Chair
PhD, Endocrinology, University of
California, San Francisco
Overall Research Interests
My overall research interest is the physiologic adaptations to pregnancy and effects of maternal physiology on fetal maturation and growth. The laboratory is focusing on changes related to the effects of the adrenal hormone cortisol in late gestation. This hormone acts on two receptor types, the glucocorticoid and the mineralocorticoid receptor. These receptors mediate physiologic effects necessary for regulating blood glucose, blood pressure, fluid and electrolyte excretion, appetite, and mood. In women and in sheep secretion of cortisol is increased during pregnancy. We are interested in the role of the increased cortisol and its action via these receptors in two inter-related adaptations of pregnancy: changes in regulation of maternal blood pressure, fluid balance, and uterine blood flow, and changes in maternal metabolism of glucose, and in the corresponding changes in fetal physiology caused by the changes in maternal physiology. We study these using pregnant and nonpregnant ewes.
There are two major areas of funded research in the laboratory. The first are studies in the pregnant ewe to examine the interaction of the placental hormone progesterone and the adrenal hormone, cortisol in regulation of blood pressure and blood volume in pregnancy. A second area of research involves examining the physiologic significance of the increased maternal cortisol during pregnancy on the fetus. Although actions at the glucocorticoid receptors are known to be crucial for normal lung and GI development at the time of birth, we are interested in whether cortisol action at the higher affinity mineralocorticoid receptors occurs earlier in gestation and results in induction of genes important for normal fluid regulation and maturation in the fetus. These effects are related to maternal physiology, because the maternal adrenal is the major source of cortisol in fetal blood before the fetal adrenal matures near the time of birth. We have found that the normal increase in maternal cortisol is important for maternal volume expansion and normal uterine blood flow in late gestation, and contributes to fetal well-being and fetal growth. We are testing the effect of blocking cortisol action at MR and GR in the fetus to test for effects on fetal lung and kidney and on genes induced by MR and GR in late gestation. We also will investigate the role of maternally secreted cortisol on fetal glucose and fat metabolism, fetal skeletal and organ growth, and on neonatal metabolism, adiposity and responses to stress.
Reini SA, Dutta G, Wood CE, Keller-Wood M. Cardiac corticosteroid receptors mediate the enlargement of the ovine fetal heart induced by chronic increases in maternal cortisol. J Endocrinol. 2008 Aug;198(2):419-27.
Li F, Wood CE, Keller-Wood M. Adrenalectomy alters regulation of blood pressure and endothelial nitric oxide synthase in sheep: modulation by estradiol. Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R257-66.
Keller-Wood M, Powers MJ, Gersting JA, Ali N, Wood CE. Genomic analysis of neuroendocrine development of fetal brain-pituitary-adrenal axis in late gestation. Physiol Genomics. 2006 Feb 14;24(3):218-24.
Keller-Wood M, Wood CE, Hua Y, Zhang D. Mineralocorticoid receptor expression in late-gestation ovine fetal lung. J Soc Gynecol Investig. 2005 Feb;12(2):84-91.