Clinical counterpoint: gonadotropin-releasing hormone deficiency: perspectives from clinical investigation.

Advances in our understanding of the pathophysiology of Kallmann syndrome have come from an interdisciplinary approach involving developmental biology, clinical investigation, and molecular biology. It is equally clear that progress to date is but the first chapter of what will be a fascinating biological story. It now seems likely that the full expression of reproductive potential from the neuroendocrine perspective is likely to be as complicated as other aspects of reproduction, such as the multigene control of external genital differentiation. An analogous story may well emerge for the neuroendocrine control of reproduction in which the GnRH gene is encoded on the eighth chromosome, the protein guiding the embryonic journey of the GnRH-producing neuron to the hypothalamus lies on the X chromosome, and many, as yet to be determined, other genetic loci collaborate in the full expression of reproductive potential. Such a detailed study is warranted not only because of the clinical and genetic implications for an individual patient with this disorder, but also from an organizational theme for the evolution of the species (and its potential regulation). Given the pressing nature of world population growth, obtaining such understanding and its applications to fertility and contraception is crucial. These advances will only come from enlightened interactions of clinical investigators, molecular geneticists, and developmental biologists in which interdisciplinary approaches should be fostered. This should be an exciting story to follow given the remarkable nature of the tools at hand to study these clinical conditions.