Contact Information

UCLA Neurobiology
Box 951763, 73-074 CHS
Los Angeles, CA 90095-1763
On-campus mail: 176318
Tel: (310) 206-8265
Fax:(310) 825-2224
E-mail: pmicevych@mednet.ucla.edu

Biosketch

Dr. Micevych is a neuroendocrinologist. He received his doctorate from the University of Minnesota and did his postdoctoral training in the Department of Neurologic Surgery at the Mayo Clinic. Dr. Micevych is currently a Professor in the Department of Neurobiology and a member of the Mental Retardation Research Center and the Laboratory of Neuroendocrinology of the Brain Research Institute at UCLA. The primary focus of his research program is to elucidate the extra- and intracellular signaling pathways used by estrogen and progesterone in nervous tissue.

Currently, there are four research concentrations in Dr. Micevych's laboratory, which are funded by three NIH R01 grants. Estrogen receptors are known to be widely distributed in neural tissue, however, except for a few regions in the hypothalamus and limbic system, the physiology of this estrogen sensitivity is unknown.

1) Most relevant to the Center is Dr. Micevych's work on estrogen's actions on intracellular signaling in DRG neurons. Concentrating on small to medium sized DRG neurons that are the cell bodies of primary afferents that signal nociception, Dr.Micevych's team has demonstrated that estrogen blocks the actions of ATP. ATP is a putative pain signal that is released following distention of the viscera. In the DRG, ATP induces intracellular calcium transients which are the proximal intracellular events signaling nociception. Estrogen rapidly blocked the ATP-induced opening of the L-type voltage gated calcium channel. Estrogen acts equally well on DRG neurons from males and females; however, in males, DRG neurons are not exposed to estrogen but in females, DRG neurons are cyclically bathed in estrogen, which may account for sex differences in pain perception. These experiments are continuing to define the estrogen receptor mediated the estrogen attenuation of ATP signaling, and characterizing the calcium and cAMP response to ATP when DRG neurons are exposed to estrogen and opioid input.

2) Building on the well worked out anatomy and physiology of limbic-hypothalamic circuits controlling sexual receptivity, we are defining the neurochemistry of these circuits. Recent findings indicate that estrogen in addition to stimulating gene transcription activates inhibitory opioid circuits to unsure appropriate timing of the sexual receptivity with ovulation. Using the internalization of opioid and NPY receptors, Dr. Micevych has demonstrated that circuits previously thought to be redundant are in fact activated in a hierarchical pattern.

3) One of the mysteries of neuroendocrinology has been the positive feedback of estrogen to induce the luteinizing hormone (LH) surge. Dr. Micevych's team has demonstrated that the LH surge is dependent on the de novo synthesis of progesterone in the hypothalamus. Rising levels of peripheral estrogen stimulate hypothalamic cells among the including astrocytes to increase their synthesis of progesterone that is secreted to act on estrogen induced progesterone receptors in neurons that mediate the stimulation of the GnRH neurons initiating the LH surge.

4) In addition to activating neurotransmitter/neuropeptide circuits, estrogen stimulates insulin-like growth factor-1 (IGF-1) and its receptor in the CNS. We have demonstrated that the action of estrogen to protect nigrostraital dopaminergic neurons from 6-hydroxydopamine lesions (6-OHDA) is dependent on IGF-1. In fact, in the 6-OHDA model of Parkinson's Disease, IGF-1 alone is as efficacious as estrogen for nigrostriatal neuroprotection.

Dr. Micevych's teaching effort has been concentrated in the medical microscopic anatomy and cell biology course, until recently when he has shifted his focus to graduate teaching. He currently participates in neurobiology courses on the structure of the nervous system and neuroendocrinology. He is course chair of a course in neural regulatory systems and the Functional Neuroanatomy course for dental students.

Dr. Micevych has trained 7 graduate students and 14 postdoctoral fellows. His laboratory is always filled with undergraduate students learning about research first hand as part of the BRIDGE, CARE and Student Research Programs. A substantial portion of his time is devoted to professional and administrative service, including organizing and program committees for several meetings, UC and UCLA Committees on Privilege & Tenure, and chairs the Department of Neurobiology Academic Review Committee.

Selected References

Sinchak K and Micevych PE. Progesterone blockade of estrogen activation of :-opioid receptors regulates reproductive behavior. J. Neuroscience, 21(15): 5723-5729, 2001.

Micevych, P, Chaban V, Quesada A, and Sinchak K. Functional interactions of CCK and µ-opioid receptors. Pharmacol & Toxicol., 91: 387-397, 2002.

Micevych, P, Rissman E, Macias L and Sinchak K. Estrogen receptor-" is required for estrogen-induced :-opioid receptor internalization. J. Neuroscience Research, 71(6): 802-810, 2003.

Chaban VV, Mayer EA, Ennes HS and Micevych PE. Estradiol inhibits ATP-increased [Ca2+]i in DRG ganglion neurons. Neuroscience, 118: 941-948, 2003.

Micevych, PE, Sinchak K, Mills RH, Tao L, LaPolt P and Lu JKH. The luteinizing hormone surge is preceded by an estrogen induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats. Neuroendocrinology, 78: 29-35, 2003.

Sinchak, K, Mills RH, Tao L, LaPolt P, Lu JKH and Micevych PE. Estrogen induces de novo progesterone synthesis in astrocytes Dev. Neuroscience, 25: 343-348, 2003.

Sinchak K and Micevych PE. Visualizing activation of opioid circuits by G protein coupled internalization. Mol Neurobiol. 27: 197-222, 2003.