Dean Meyers

 

Associate Professor of Obstetrics and Gynecology,
Adjunct Associate Professor of Cell Biology,
Adjunct Associate Professor of Physiology,
The John Records Chair in Maternal-Fetal Medicine.

EDUCATION

B.S., Fort Hayes State

M.S., Laramie, Wyoming

Ph.D., Laramie, Wyoming


RESEARCH SUMMARY

Synthesis of the steroid hormone, cortisol (corticosterone in rodents), in the fetal adrenal glands initiates in utero during late gestation. Consequently, in nearly every mammalian species there is a dramatic rise in fetal glucocorticoid (cortisol/corticosterone) levels in the final days of gestation. Glucocorticoids are essential for initiating the expression of numerous genes in various organs that provide functionality to those organs- in essence, organ maturation (eg. lungs) thus allowing the fetus to live ex-utero post-birth. My laboratory has two central areas of research focusing on development of the hypothalamic-pituitary adrenal axis and the mechanism via which glucocorticoids regulate gene expression.

1) Endocrine, molecular and cellular mechanisms governing the development of the adrenal cortex.
Cortisol is produced from cholesterol via a series of sequential enzymatic steps. There are two key cytochrome P450 family enzymes, CYP11A1 (side chain cleavage) and CYP17 (17 alpha hydroxylase), which are rate limiting in the formation of cortisol. The induction of these enzymes during adrenal maturation is dependent upon the 39 amino acid anterior pituitary hormone, adrenocorticotropic hormone (ACTH), which in turn is regulated by the hypothalamic neuropeptide, corticotropin releasing hormone (CRH). We are studying the cellular and molecular mechanisms via which ACTH regulates the induction of expression of CYP11A1 and CYP17 during adrenal development. In related studies, we are examining the effect of development under adverse conditions (hypoxia and maternal undernutrition) on development of the adrenal gland.

2) Environmental ‘programming' of corticotropin releasing factor (CRF) neurons.

We are examining mechanisms via which CRH neurons differentiate and how premature exposure of the developing fetus to glucocorticoids or maternal stress alters the development of these neurons leading to later dysfunction of the stress axis and hypersecretion of glucocorticoids. Excessive glucocorticoid production promotes hypertension, hyperglycemia, insulin resistance, visceral adiposity and dyslipidemia (metabolic syndrome X). Thus programming of CRH neurons (both number of CRH neurons and the level of CRH expression) represents a potential mechanism for the development of the cardiovascular and metabolic disorders resulting from exposure to an adverse intrauterine environment. Specifically, we are studying the role of histone modifications (acetylation, methylation, phosphorylation and use of histone variants) in nucleosomes positioned in the CRH promoter in sensitivity of the CRH gene to transcriptional activation and the mechanisms governing the histone ‘code' of the CRH promoter.

SELECTED PUBLICATIONS

1. Shepard J.D., Barron K. and Myers D.A. 2000. Corticosterone delivery to the amygdala increases corticotropin releasing factor mRNA in the central amygdaloid nucleus and anxiety-like behavior. Brain Research 861:288-295.

2. Shepard J.D., Barron K.W. and Myers D.A. 2003. Stereotaxic delivery of corticosterone to the amygdala modulates corticotropin releasing factor mRNA levels in the hypothalamic paraventricular nucleus and the adrenocortical response to stress. Brain Research 963:203-213.

3. Myers, D.A., Bell P. Mlynarczyk, M. and Ducsay C.A. 2005. Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus. Am. J. Physiol 288:R1178-1184.

4. Bell, M.E., McDonald T.J. and Myers, D.A. 2005. Proopiomelanocortin processing in the anterior pituitary of the ovine fetus after lesion of the hypothalamic paraventricular nucleus. Endocrinology 146:2665-2673.

5. Myers, D.A., Bell P., Mlynarczyk, M. and Ducsay. C. A. 2005. Long-term hypoxia represses the expression of genes regulating cortisol biosynthesis in the near-term ovine fetus. Am J. Physiol. 289:R1707-1714.

6. Ducsay C.A., Mlynarczyk, M., Hyatt, K. and Myers, D. A. 2006. Long-term hypoxia increases leptin receptors and plasma leptin concentrations in the late gestation ovine fetus. American Journal of Physiology 291:R1406-1413.


MAILING ADDRESS

Presbyterian Health Foundation Research Park

800 Research Parkway

RP1 468

Oklahoma City, OK 73126

Phone: (405) 271-2286

Dean-Myers@ouhsc.edu