Spring 1996 Volume 5, Number 2
In an October, 1893 letter to W. Fleiss about his theories of sex-related dysfunctions, Sigmund Freud wrote, "to investigate the genitals and the nose simultaneously; the riddle should be solved in no time."
Now science has caught up with Freud's hypothesis: A human syndrome, idiopathic hypothalamic hypogonadism (a key form of which is "Kallmann's Syndrome"), shows the relationship is there even before birth. Kallmann's syndrome includes primarily the inability to smell (anosmia) and abnormal development of the gonads (hypogonadotrophic hypogonadism).
The anosmia results from a failure in formation of connections between nerve fibers from the nose and the brain; the gonadal dysfunction comes from insufficient secretion of a key peptide, gonadotropin releasing hormone (GnRH), which is made by neurons in the brain's hypothalamus.
The surprising link is that, in the vast majority of vertebrates, including man, the neurons that make GnRH are born in the nasal compartment and migrate into the brain toward the hypothalamus along "roads" supplied by the olfactory system.
Studies by Stuart Tobet, Gary Schwarting and colleagues at The Shriver Center show that the sense of smell and reproduction are so fundamentally linked that in certain ways olfactory system development is inseparable from GnRH cell migration and development.
Using cultures of embryonic mouse heads, Tobet's team is investigating the normal migration of GnRH neurons from the nasal compartment into the brain compartment. Their experiments show that, when they disrupt fibers between the two compartments, they also disrupt GnRH neuron migration, producing a replica of Kallmann's syndrome in a dish. Their next step will be to identify the specific factors that lead GnRH neurons across the olfactory road into the brain --a step toward understanding the origins of reproductive abilities.
