Jon Levine

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.

Full list of publications can be found here.