The Levine Lab

Laboratory of Neuroendocrinology

Neuroendocrinology is the study of two basic types of biomedical questions: How does the brain control the production and release of hormones? How do hormones act in the brain to regulate physiology and behavior? Research in the Levine laboratory includes studies of both types, particularly as they relate to reproductive neuroendocrine systems that control fertility, reproductive behaviors, and social behaviors..

Much of our research focuses on 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.

We are particularly interested in 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 and neural development.

Several of our studies also address the molecular and cellular mechanisms that mediate sex steroid hormone effects on behavior. The role of progesterone and its receptors in regulating feeding behavior is the subject of one such study; in this project we are attempting to understand the regulation of appetite by progesterone during pregnancy. In another set of studies we have determine that progesterone receptors, previously thought to be important only in female physiology and behavior, play important roles in the regulation of social behaviors in male animals. We are using genetically modified animals to further delineate the involvement of progesterone receptors in paternal behavior, aggression towards young, social recognition, and affiliative behaviors.