Email: physiology@rosalindfranklin.edu Fax: 847.578.3265
Hawkins, Richard A Kim, Donghee
Najmabadi, Feridoon McCormack, Charles E. Peterson, Darryl R. Rasgado-Flores, Hèctor
The focus of my research is on the molecular and cellular mechanisms underlying the control of neuroendocrine and cardiovascular function in males and females. Exposure to stressful conditions results in the activation of central corticotropin releasing factor (CRF) neurons that increase the release of adrenocorticotropin hormone (ACTH) from the pituitary ultimately leading to increases in cortisol/corticosterone secretion from the adrenal gland. The activity of CRF neurons is controlled by a number of different factors including steroid hormones, central peptidergic neurons and neurotransmitters such as norepinephrine and serotonin. One neuropeptide factor that we are particularly interested in is neuropeptide Y (NPY). NPY is widely distributed in the brain and peripheral nervous systems and plays an integral role in the regulation of stress and reproductive hormone secretion, the sympathetic nervous system and the perception of anxiety. There are at least 6 subtypes of NPY receptors (Y1-Y6) which are differentially expressed within the brain and peripheral nervous system.
Current projects in the laboratory are focussed on identifying the distribution of NPY receptors within stress responsive areas (such as the arcuate and paraventricular nucleus of the hypothalamus, and central and basolateral amygdala) and the extent to which these receptors contribute to neuroendocrine function. Additional studies focus on the regulation of NPY and its receptors by stress and whether drugs that are prescribed for mood disorders such as anxiety and depression (serotonin uptake inhibitors; i.e. Prosac and Paxil) alter the distribution and expression of NPY and NPY receptors. Along these lines, studies have indicated that there are sex differences in the neuroendocrine responses to stress. We have previously shown that NPY systems are modulated by the presence of androgens in males and estrogen and progesterone in females. We intend to investigate further whether steroid modulation of NPY systems may contribute to the sex differences observed in stress responses. Some of the techniques employed in the research include in situ hybridization, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR), receptor binding and radioimmunoassay.
Photomicrograph showing NPY mRNA expressing cells in the arcuate nucleus of the hypothalamus of a male (A) and female (B) rat. Note that the arcuate nucleus of the male rat contains significantly more NPY mRNA expressing cells than a comparable section from a female rat.
Recent Publications
Urban J.H., Bauer-Dantoin A.C. and Levine J.E.: Neuropeptide Y gene expression in the arcuate nucleus: sexual dimorphism and modulation by testosterone. Endocrinology 132:139-145 (1993).
Urban J.H., Das I., Levine J.E.: Regulation of luteinizing hormone releasing hormone in intact and castrate male rats by neuropeptide Y (NPY). Neuroendocrinology 63:112-119 (1996).
Porkka-Heiskanen T., Khoshaba N., Scarbrough K., Urban J.H., Vitaterna M.H., Levine J.E., Turek F.W., Horton, T.H.: Rapid photoperiod induced changes in the number of detectable GnRH mRNA containing cells in the Siberian Hamster. Am. J. Physiol. 273(6 Pt 2):R2032-9 (1997).
Mukherjee A., Urban J.H., Sassone-Corsi P., Mayo K.E.:Gonadotropins Regulate Inducible cAMP Early Repressor (ICER) mRNAs in the Rat Ovary: Implications for Inhibin Subunit Gene Expression. Molecular Endocrinology 12:785-800 (1998).
Urban J.H. : Assessment of neuropeptide receptor gene expression using reverse transcriptase polymerase chain reaction. In Methods in Neuroendocrinology, ed. L.D. Van de Kar, New York. pp 18-30 (1998).
Xu M., Urban J.H., Hill J.W., Levine J.E.: Regulation of hypothalamic neuropeptide Y Y1 receptor gene expression during the estrous cycle: role of progesterone receptors. Endocrinology 141:3319-3327 (2000).
Wolak ML, deJoseph MR, Brownfield MS, Urban JH: Distribution of neuropeptide Y Y1 and Y5 receptors in the rat brain using immunohistochemistry. Submitted.
Wolak ML, deJoseph MR, Brownfield MS, Grouzmann E, Urban JH: Colocalization of NPY and NPY Y1 receptor immunoreative cells in the adrenal gland. Submitted.