Menu UF Health Home Menu
 

Charles E. Wood, Ph.D.

Professor and Chair

Charles E. Wood, Ph.D.

Charles E. Wood, Ph.D.

(352) 294-5064
Office: MSB M556
woodc@ufl.edu
PubMed Listing

The research performed in the laboratory of Dr. Charles Wood is focused on the mechanisms controlling the responses to stress in the fetus in utero and on the mechanisms controlling the timing of birth. These two areas of research are related because both involve the neuroendocrinology of the fetal hypothalamus-pituitary-adrenal (HPA) endocrine axis, as well as other hormonal systems. This laboratory has published research results which have played a leading role in elucidating the function of the fetal arterial baroreceptors and chemoreceptors in the control of fetal cardiovascular and endocrine function. Other research performed in this laboratory has identified the cardiovascular neural receptors which are involved in the integrated cardiovascular and endocrine response to alterations in blood gases and blood pressure in the fetus. Other, more purely endocrine experiments performed in this laboratory, have demonstrated important changes in the sensitivity of cortisol negative feedback regulation of fetal adrenocorticotropic hormone (ACTH) secretion which allow parturition in term fetuses. The discovery that the sensitivity of the fetal hypothalamo-pituitary unit to the negative feedback effects of cortisol decreases just prior to the term has been widely recognized as the discovery of an important link in the chain of events which initiates the process of labor and delivery. A recent publication from this laboratory has, however, also demonstrated that unprocessed or partially processed forms of ACTH are synthesized and released by peripheral fetal tissues, most notably the fetal lung, leading to the hypothesis that fetal visceral maturation might influence the timing of birth via the release of endocrine signals which modify the basic endocrine mechanism of parturition.

Present work in this laboratory focuses on three projects: 1) the interaction of prostanoids with the cardiovascular and endocrine controlling elements of the brain and the role of the locally-generated prostanoids in brain in the control of fetal stress responses (hypoxia and hypotension); 2) the influence of estrogen on the fetal brain regions which are important for cardiovascular and endocrine responsiveness to stress; and 3) the biological activity of sulfoconjugated estrogens in fetal plasma. This work is predicated on the observation that the fetal HPA axis is involved both in coordinating fetal stress responses (and thus is involved in the fetal survival of stress) and in coordinating the initiation of parturition. Identifying the basic neural mechanisms controlling fetal HPA function will yield a better understanding of both processes, as well as providing new strategies for therapeutic interventions. On this basic level, information gained in the ovine model will likely be directly applicable to the human being. We have found that prostaglandins generated within the fetal brain exert a profound influence on fetal HPA activity. The fetal response to hypotension, for example, is partially blocked using an inhibitor of prostaglandin biosynthesis. Hypotension stimulates the biosynthesis of the inducible form of the enzyme critically important for prostaglandin biosynthesis, cyclooxygenase-2 (COX-2), within the pathways in the fetal brain which impinge on the paraventricular nucleus, which sits at the head of the HPA axis. However, we have also reported that the expression of both COX-1 and COX-2 are increased in these regions as a function of development, supporting the notion that the increase in HPA axis activity which initiates parturition is itself dependent upon prostaglandin production. Recently, we have explored this ontogenetic regulation by demonstrating that fetal estrogen, which is released by the placenta prior to term, augments COX-2 expression in fetal brainstem and hypothalamus. Finally, we have initiated studies which demonstrate that estradiol-3-sulfate, the most abundant estrogen in fetal plasma, yet a steroid which has long been thought to be inactive, is converted in the fetal brain to its active form, 17β-estradiol, where it increases HPA axis activity. All of these studies, which are funded on multiple extramural grants, interrelate to each other and will provide a more mechanistic understanding of fetal stress and parturition than we currently have. The ultimate goal is to identify interventional strategies which can manipulate the timing of birth while avoiding the pitfalls encountered with current treatments.