Oline K. Rønnekleiv
The Rønnekleiv lab is investigating the function and regulation of gonadotrophin releasing hormone (GnRH) neurons. The GnRH neurons control reproduction and are therefore critical for the survival of the species. These neurons migrate from the nose during development to their species-specific location in the hypothalamus (Rønnekleiv and Resko, Endocrinology, 1990). For our studies we are combining whole-cell patch recording with single cell (sc) harvesting and scRT-PCR to explore membrane properties, intracellular signaling cascades and gene expression in individual neurons. We have shown that the mRNA expression and function of ion channels, important for burst firing in GnRH neurons, are regulated by 17ß-estradiol (E2). Our current work focuses on the mechanism by which the upstream peptide, kisspeptin, induces burst firing and GnRH release. To date, kisspeptin neurons provide the most potent excitatory drive to GnRH neurons, and it is known that patients with deletion in its cognate receptors GPR 54 (Kiss1 receptor) exhibit hypothalamic hypogonadism.
The lab is also studying the role of E2 and STX (the selective ligand for a putative membrane estrogen receptor) in modulating hypothalamic control of temperature and energy homeostasis in a number of animal models including guinea pig and rhesus monkey. Current studies in collaboration with Dr. Martin Kelly are focused on E2 and STX regulation of proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons that have opposing roles in the control of feeding and metabolism. In addition, they have recently embarked on studies of arcuate kisspeptin neurons and the interaction between E2, leptin and insulin acting though multiple signaling cascades to affect kisspeptin neuronal excitability and ultimately the reproductive cycle. we have active collaborations with a number of investigators at the Oregon National Primate Research Center including Drs. Sergio Ojeda, Cynthia Bethea, Henryk Urbanski, Martha Neuringer, Steven Kohama and Susan Smith.
Dr Rønnekleiv received her Ph.D. in Physiology from UT Southwestern Medical School (1974). After one year of postdoctoral training at UCLA she did a three-year Alexander von Humboldt-funded fellowship at the Max Planck Institute for Biophysical Chemistry in Gøttingen, Germany. Dr. Rønnekleiv joined the faculty at the University of Pittsburgh School of Medicine as an Assistant Professor in 1979 and moved to OHSU in 1982. She as promoted to Associate Professor in the Department of Physiology in 1987 and Associate Scientist in the Division of Neuroscience at ONPRC in 1991. Dr. Rønnekleiv was promoted to full Professor of Physiology and Pharmacology in 1998, Senior Scientist at ONPRC in 2000 and Professor of Anesthesiology and Perioperative Medicine in 2007. She has maintained an active (NIH-funded) research program since 1982.
Gottsch ML, Popa SM, Lawharon JK, Qiu J, Tonsfeldt KJ, Bosch MA, Kelly MJ, Rønnekleiv OK, Sanz E, McKnight GS, Clifton DK, Palmiter RD, Steiner RA. (2011) Molecular properties of kiss1 neurons in the arcuate nucleus. Endocrinology. 152(11):4298-4309. PMID: 21933870. PMCID: PMC3199004.
Bosch MA, Xue C, Rønnekleiv OK. (2012) Kisspeptin expression in guinea pig hypothalamus: Effects of 17ß-estradiol. J Comp Neurol. 520(10):2143-2162. PMID: 22173890. PMCID: PMC3571706.
Bosch MA, Tonsfeldt KJ, Rønnekleiv OK. (2013) mRNA expression of ion channels in GnRH neurons: Subtype specific regulation by 17β-estradiol. Mol Cell Endocrinol. 367(1-2):85-97. PMID: 23305677. PMCID: PMC3570747.
Zhang C, Rønnekleiv OK, Kelly MJ. (2013) Kisspeptin inhibits a slow afterhyperpolarization current via protein kinase C and reduces spike-frequency adaptation in GnRH neurons. Am J Physiol Endocrinol Metab. 2103 Apr 2. [epub ahead of print]. PMID: 23548613. In Press.