Kallmann Syndrome and the Link between Olfactory and Reproductive Development

Abstract

The sense of smell mediates communication with the external environment through the recognition of chemical cues. In mammals, olfactory chemosensation begins in sensory neurons located in the olfactory epithelium, which lines the olfactory turbinates inside the nose, and in the epithelium of the vomeronasal organ (VNO), a tubular structure that opens on the ventral aspect of the nasal septum. Neurons in the olfactory epithelium detect volatile odorants, providing information about the external milieu, whereas sensory neurons located in the VNO detect pheromones, nonvolatile chemical signals that trigger innate and stereotyped reproductive and social behaviors, as well as neuroendocrine changes. Olfactory and vomeronasal neurons project their axons to the main and the accessory olfactory bulbs, respectively, where they synapse with dendrites of mitral and tufted cells in specialized structures called “glomeruli” (Farbman 1992). The presence of a potentially functional VNO in humans has been recently documented, but whether humans use this system to process and to respond to chemical signals emitted by other members of the species remains controversial (Dulac and Axel 1995; Berliner et al. 1996; Herrada and Dulac 1997; Monti-Bloch et al. 1998; Stern and McClintock 1998). However, regardless of the role of the VNO as a sensory organ in our species, it is now clear from the study of the X-linked disorder Kallmann syndrome (MIM 308700, MIM 147950, and MIM 244200) that development of the olfactory and vomeronasal system is required for normal sexual maturation. Here, I review studies by neurobiologists, particularly those working in the developing chick, as well as the human genetic analysis that has brought this surprising connection to light.