Development of a sexually differentiated behavior and its underlying CNS arousal functions.

This chapter addresses questions regarding lordosis behavior, the most extremely sexually differentiated behavior that has been analyzed for its neural and molecular mechanisms. Analysis of this behavior has proved for the first time that specific biochemical reactions in specific nerve cell groups in the brain determine a mammalian behavior. Lordosis is done by the female but not by the male. How did the process of sexual differentiation occur? A large literature implicates high levels of testosterone during a critical period during development as being responsible for the defeminization of the brain. A new idea, however, offers the possibility of direct genetic influences independent of testosterone levels themselves. We propose here that Mullerian Inhibiting Substance (MIS) and its receptors could constitute an example of a nonandrogenic genetic influence. Further, specific sexual behaviors depend on underlying arousal states in the central nervous system (CNS). We have proposed the concept of generalized CNS arousal and provide information as to how generalized arousal forces interact with specifically sexual influences, thus to facilitate sexually differentiated mating behaviors.

Anosmin-1 immunoreactivity during embryogenesis in a primitive eutherian mammal.

Kallmann syndrome is hypogonadotropic hypogonadism coupled with anosmia. A morphological study found that the endocrine disorder in X-linked Kallmann syndrome is due to failed migration of gonadotropin releasing-hormone (GnRH) neurons from the olfactory placode to the brain during development. Anosmia results from agenesis of the olfactory bulbs and tracts. The gene responsible for the X-linked form of Kallmann syndrome, KAL-1, has been characterized. The orthologues of KAL-1 have been isolated in the chick and the zebrafish, but still await identification in rodents. In the present study, we used polyclonal and monoclonal antibodies to the human KAL-1 encoded protein, anosmin-1, in a primitive mammal, the Asian musk shrew. Musk shrews are insectivores and are therefore evolutionarily closer to primates than rodents. By immunoblot analysis of musk shrew tissues, a band of the expected apparent molecular mass (95 kDa) was detected in several structures of the central nervous system, but not in liver or muscle, which is consistent with the gene expression pattern previously reported in the chick. By immunohistochemical analysis, anosmin-1 was detected in the developing olfactory epithelium, the olfactory, vomeronasal and terminalis nerves, the olfactory bulbs, the cerebellum and the cerebral cortex and in several other regions of the brain, during musk shrew embryogenesis. Furthermore, migrating gonadotropin releasing-hormone (GnRH)-immunoreactive neurons were seen in close association with anosmin-1-immunoreactive fibers. Assuming that the protein is present at the surface of these fibers, we suggest a possible direct role of anosmin-1 in the migration of GnRH neurons in this species.