Rick McCosh

I am fascinated by connections between the brain and body, particularly regarding the reproductive system and stress responses. Reproduction and the response to stress are dependent on complex interactions between peripheral tissues and the central nervous system. Research in my laboratory is focused on dissecting the neural pathways that alter gonadotropin secretion and therefore regulate fertility, including how stress impairs gonadotropin secretion. In mammals, modulation of luteinizing hormone (LH) secretion determines fertility and controls gonadal steroid production, which has profound effects on cardiovascular, musculoskeletal, and mental health. LH is secreted in two distinct patterns dictated by two populations of kisspeptin cells in the hypothalamus. The pulsatile pattern of LH secretion occurs in males and in females throughout most of the ovarian cycle and is dependent on neurons in the arcuate nucleus that co-express Kisspeptin, Neurokinin B and Dynorphin (KNDy cells). The preovulatory LH surge is induced by estradiol in females and is dependent upon kisspeptin cells in the rostral periventricular area of the third ventricle (RP3VKiss1) in mice, or preoptic area in sheep. To date, the neural pathways that transmit signals from the periphery to regulate kisspeptin cells and modulate LH secretion remain unclear. Some of the questions we pursue are: (1) what are the cellular and molecular components of the GnRH pulse generator and GnRH surge-induction system?; (2) what stimuli (e.g. stress) alter gonadotropin secretion?; (3) how are these stimuli sensed and conveyed to the GnRH pulse generator or GnRH surge-induction system?; and (4) how do gonadal steroids influence sensitivity to these stimuli? To address these questions we use molecular, cellular, and integrative approaches in sheep, mice, and cell culture models.