Victor Navarro, MD

Institution: Brigham and Women's Hospital, Harvard Medical School
Research: Neuroendocrine Regulation of Metabolism and Reproduction
Grants & Publications: Harvard Catalyst
Categories: BWH, HMS

The Navarro lab focuses on the neuronal mechanisms that control reproductive function and metabolism, from the events that participate in the sexual differentiation of the brain during perinatal periods to the acquisition and maintenance of reproductive behavior and fertility, as well as the metabolic cues that control each of these critical processes.

Reproduction is coordinated by neuro-endocrine communication between the brain and gonads. The hypothalamus is the nodal point for the action of central and peripheral factors that control the secretion of neurons that produce gonadotropin-releasing hormone (GnRH). GnRH stimulates the pituitary to secrete LH and FSH, which then act on the gonads to induce gametogenesis and create sex steroids, which in turn feedback to the hypothalamus to control GnRH release. Although we understand the basic principles that govern reproduction, we know far less about the cellular and molecular mechanisms that control GnRH secretion. Thus, the focus of the Navarro Lab is to understand how hormones and neurotransmitters initiate the onset of puberty, regulate reproductive cycles, and integrate metabolism and reproduction with special attention to the Kiss1 system.

Kisspeptins, encoded by the Kiss1 gene, bind to a G protein-coupled receptor, Kiss1r (formerly called GPR54). The importance of this signaling pathway became evident in 2003, when inactivating mutations in the Kiss1r gene were linked to hypogonadotropic hypogonadism in humans and mice. GnRH neurons are direct targets for the action of kisspeptin, which is a potent secretagogue for GnRH. The Navarro Lab continues the line of research that initially demonstrated that the expression of Kiss1 and Kiss1r in the hypothalamus is induced in association with the onset of puberty and that the administration of kisspeptin to prepubertal animals can initiate precocious puberty, suggesting that the kisspeptin activation of GnRH neurons plays a key role in gating pubertal maturation. Additionally, these initial studies showed that the expression of the Kiss1 gene of the adult is influenced by the steroid milieu during the neonatal critical period, when the brain undergoes sexual differentiation.
We are also interested in elucidating the hypothalamic pathways that regulate the action of the Kiss1 system. Specifically, the action of dynorphin (encoded by Pdyn) and tachykinins (Substance P, neurokinin A and neurokinin B, encoded by Tac1 and Tac2) on Kiss1 neurons. Many of these neurotransmitters are co- expressed in the same neurons of the hypothalamic arcuate nucleus and are suggested to participate in the shaping of kisspeptin pulses, which in turn control GnRH pulsatility.