Molecular, cellular, and physiological aspects of peptidergic neuronal function; reproductive neuroendocrinology

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.

e-mail Dr. Levine
ph: 847.491.7180
fax: 847.491.2523

• Glidewell-Kenney C, Weiss J, Hurley LA, Levine JE, Jameson JL. (2008). Estrogen receptor alpha signaling pathways differentially regulate gonadotropin subunit gene expression and serum follicle-stimulating hormone in the female mouse. Endocrinology. 149(8):4168-76.

• Foecking EM, McDevitt MA, Acosta-Martínez M, Horton TH, Levine JE. (2008). Neuroendocrine consequences of androgen excess in female rodents. Horm Behav. 53(5):673-92.

• Zhang C, Bosch MA, Levine JE, Rønnekleiv OK, Kelly MJ. (2007). Gonadotropin-releasing hormone neurons express K(ATP) channels that are regulated by estrogen and responsive to glucose and metabolic inhibition. J Neurosci. 19;27(38):10153-64.

• McDevitt MA, Glidewell-Kenney C, Weiss J, Chambon P, Jameson JL, Levine JE. (2007). ERE-independent ER{alpha} signaling does not rescue sexual behavior but restores normal testosterone secretion in male ER{alpha}KO mice. Endocrinology. Online.

• Glidewell-Kenney C, Hurley LA, Pfaff L, Weiss J, Levine JE, Jameson JL. (2007). Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis. PNAS U S A. 8;104(19):8173-7.
   
• Acosta-Martinez M, Levine JE. (2007). Regulation of KATP channel subunit gene expression by hyperglycemia in the mediobasal hypothalamus of female rats. Am J Physiol Endocrinol Metab. 292(6):E1801-7.
   
• Acosta-Martinez M, Horton T, Levine JE. (2007). Estrogen receptors in neuropeptide Y neurons: at the crossroads of feeding and reproduction. Trends Endocrinol Metab. 18(2):48-50.
   
• Miller BH, Olson SL, Levine JE, Turek FW, Horton TH, Takahashi JS. (2006). Vasopressin regulation of the proestrous luteinizing hormone surge in wild-type and Clock mutant mice. Biol Reprod. 75(5):778-84.

• Schwartz NB, Levine JE. (2006). Ontogeny of gonadotropin-releasing hormone neurons: fishing for clues in medaka. Endocrinology. 147(3):1074-5.

• Foecking EM, Levine JE. (2005). Effects of experimental hyperandrogenemia on the female rat reproductive axis: suppression of progesterone-receptor messenger RNA expression in the brain and blockade of luteinizing hormone surges. Gend Med. 2(3):155-65.

• Schneider JS, Burgess C, Sleiter NC, DonCarlos LL, Lydon JP, O'Malley B, Levine JE. (2005). Enhanced sexual behaviors and androgen receptor immunoreactivity in the male progesterone receptor knockout mouse. Endocrinology. 146(10):4340-8.
   
• Foecking EM, Szabo M, Schwartz NB, Levine JE. (2005). Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator. Biol Reprod. 72(6):1475-83.
   
• Miller BH, Olson SL, Turek FW, Levine JE, Horton TH, Takahashi JS. (2004). Circadian clock mutation disrupts estrous cyclicity and maintenance of pregnancy. Curr Biol. 10;14(15):1367-73.
   
• Hill JW, Urban JH, Xu M, Levine JE.  (2004). Estrogen Induces Neuropeptide Y (NPY) Y1 receptor gene expression and responsiveness to NPY in gonadotrope-enriched pituitary cell cultures. Endocrinology. 145(5):2283-90.

• Hill JW, Levine JE. Abnormal response of the neuropeptide Y-deficient mouse reproductive axis to food deprivation but not lactation. (2003). Endocrinology. 144(5):1780-6.

Other Links:

• Northwestern University Program in Biological Sciences (PBS)

• Levine lab home page