Professor - Director, Wisconsin National Primate Research Center Ph.D., University of Illinois, Urbana-Champaign
RESEARCH INTERESTS - Neuroendocrine regulation of reproduction and metabolism, steroid hormone actions on brain and behavior
My laboratory studies the synthesis, secretion, and actions of gonadotropin-releasing hormone (GnRH), a brain peptide that governs secretion of reproductive hormones from the anterior pituitary gland. We are particularly interested in the cellular mechanisms that mediate the physiological regulation of GnRH neurosecretion during the female ovulatory cycle. Our studies utilize a variety of experimental approaches and animal models to ascertain the molecular processes by which gonadal steroids, diet, stress, and neuroendocrine signals for sexual maturation can exert their effects on GnRH release. Much of our work is focused on the regulation of GnRH neurosecretion by the gonadal steroid hormones, estrogen and progesterone. Throughout the normal ovulatory cycle, these hormones exert homeostatic feedback control over GnRH neurosecretion. However, in certain reproductive and metabolic disorders, such as polycystic ovarian syndrome (PCOS), brain circuitries controlling GnRH release become resistant to these feedback control mechanisms, leading to hypersecretion of GnRH and hence, infertility. We are attempting to gain an understanding of the cellular basis of this PCOS pathophysiology, and the early developmental factors that may be responsible for its manifestation. From a broader perspective, we hope that our studies will provide new insights as to the mechanisms by which steroid hormones govern reproductive physiology, neural development, and behavior
Figure (above): Representative wild-type (left), estrogen receptor alpha knockout (center), and non-classical estrogen receptor alpha knock-in (right) mice (anesthetized), revealing the rescue of normal body weight and adiposity by non-classical estrogen receptor alpha signaling in obese knockout mice.
- Park CJ, Zhao Z, Glidewell-Kenney C, Lazic M, Chambon P, Krust A, Weiss J, Clegg J, Dunaif A, Jameson JL, Levine JE. Genetic Rescue of Nonclassical ERa Signaling Normalizes Energy Balance in Obese Era -null Mutant Mice. J Clin Invest. 2011 Feb;121(2):604-612
- Lazic M, Aird F, Levine JE, Dunaif A. Prenatal androgen treatment alters body composition and glucose homeostasis in male rats. J Endocrinol. 2011 Mar;208(3):293-300. Epub 2010 Dec 20
- Mayer C, Acosta-Martinez M, Dubois SL, Wolfe A, Radovick S, Boehm U, Levine JE. (2010) Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proc Natl Acad Sci USA. 2010 Dec 28;107(52):22693-8. Epub 2010 Dec 13. PubMed PMID: 21149719; PubMed Central PMCID: PMC3012491
- Ciofi P, Garret M, Lapirot O, Lafon P, Loyens A, Prevot V, Levine JE. (2009) Brain-endocrine interactions: a microvascular route in the mediobasal hypothalamus. Endocrinology. 2009 Dec;150(12):5509-19. Epub 2009 Oct 16. PubMed PMID: 19837874; PubMed Central PMCID: PMC2819742.
- Gottsch ML, Navarro VM, Zhao Z, Glidewell-Kenney C, Weiss J, Jameson JL, Clifton DK, Levine JE, Steiner RA. (2009) Regulation of Kiss1 and dynorphin gene expression in the murine brain by classical and nonclassical estrogen receptor pathways. J Neurosci. 2009 Jul 22;29(29):9390-5. PubMed PMID: 19625529; PubMed Central PMCID: PMC2819182
- Acosta-Martinez M, Luo J, Elias C, Wolfe A, Levine JE. (2009) Male-biased effects of gonadotropin-releasing hormone neuron-specific deletion of the phosphoinositide 3-kinase regulatory subunit p85alpha on the reproductive axis. Endocrinology. 2009 Sep;150(9):4203-12. Epub 2009 Jun 18. PubMed PMID: 19541766; PubMed Central PMCID: PMC2736084
- Singh SP, Wolfe A, Ng Y, DiVall SA, Buggs C, Levine JE, Wondisford FE, Radovick S. (2009) Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1). Biol Reprod. 2009 Sep;81(3):488-96. Epub 2009 May 13. PubMed PMID: 19439729; PubMed Central PMCID: PMC2731984.
- Sleiter N, Pang Y, Park C, Horton TH, Dong J, Thomas P, Levine JE. (2009) Progesterone receptor A (PRA) and PRB-independent effects of progesterone on gonadotropin-releasing hormone release. Endocrinology. 2009 Aug;150(8):3833-44. Epub 2009 May 7. PubMed PMID: 19423765; PubMed Central PMCID: PMC2717864
- Zhao Z, Park C, McDevitt MA, Glidewell-Kenney C, Chambon P, Weiss J, Jameson JL, Levine JE. (2009) p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis. Proc Natl Acad Sci USA. 2009 Apr 28;106(17):7221-6. Epub 2009 Apr 9. PubMed PMID: 19359483; PubMed Central PMCID: PMC2667369.
- McDevitt MA, Thorsness RJ, Levine JE. (2009) A role for ATP-sensitive potassium channels in male sexual behavior. Horm Behav. 2009 Feb;55(2):366-74. Epub 2008 Sep 16. PubMed PMID: 18950632