Neuroendocrine Mechanisms Regulating Reproductive Transition in the Ruminant Female: Is KNDy Required?

States of reproductive transition in female livestock represent important and economically significant periods of physiological change that have major impacts on the efficiency and success of breeding and production programs. These include, but are not limited to, the process of sexual maturation, postpartum resumption of ovarian cycles, and cyclical recrudescence in seasonal breeding species. Over the last four decades, our laboratory has focused primarily on determining the fundamental neuroendocrine mechanisms controlling states of reproductive transition in bovine and equine models, and applying principals learned to develop managerial approaches for positive intervention. The objectives of this presentation are to briefly review our understanding of external and internal signaling pathways that regulate two of these transitional states in the bovine female, postpartum resumption of ovulatory cycles and pubertal development. The focus will be to consider contrasts and commonalities of hypothalamic-pituitary signaling pathways that govern the temporal trajectories of these processes, with particular emphasis on those pathways that modulate the GnRH pulse generator. Notably (and until recently), the pulse generator has been a poorly defined “black box” with respect to its cellular origin and neurochemical character. Thus, the synchronous pattern of GnRH neuronal depolarization, multiunit electrical activity, and release of GnRH for the control of gonadotropins have been accepted as intrinsic features of GnRH neurons themselves. However, the identification of the neuropeptide kisspeptin in 1996, and more recently (2007) the description of a specialized population of kisspeptin-secreting neurons in the medial basal hypothalamus, termed KNDy neurons, have provided convincing evidence for an extrinsic source of pulse generation within the arcuate/infundibular region. How do KNDy neurons serve in this function, what is their role in transducing environmental, nutritional, and behavioral signals during transitional states, and what is the potential for neuropeptides of KNDy neuron origin to serve as pharmacological agents to control reproduction?