An important mechanism for coordinating sexual performance in mammals is the occurrance of endocrine changes in response to particular external stimuli, and the cord process underlying those changes is hypothalamic control of pituitary gonadotropin release. The components of the central nervous system that connect sensory inputs with gonadotropin release therefore constitute a major black box in neuroendocrinology. Importantly, social interactions between members of a population provide potent cues which operate through that black box to modulate gonadotropin release. For example, species specific odors (pheromones) disseminated by females are detected by the vomer nasal system and enhance luteinizing hormone (LH) and testosterone secretion in male rodents. Those facts provide an excellent system for studying the linkage between a known external stimulus and the neuroendocrine reflex which it evokes. This proposal focuses on the central neural tracts that mediate male's LH reflexes in response to female pheromones.
The specific aims are (i) to delineate that pathway anatomically and (ii) to identify the neurochemicals that mediate its actions. Male mice are especially suitable to study because female urinary odors elicit dramatic LH pulses which have been thoroughly examined. Manipulations such as discrete deafferentations and electrolytic lesions will be used to identify the brain nuclei that participate in the reflexive LH pulses. Projections from those areas toward LH-releasing hormone (LHRH) neurons will be traced by orthograde transport of labelled molecules combined with immunohistochemical localization of LHRH. To define the pathway neurochemically, reflexive and spontaneous LH pulses will be differentially inhibited by pharmacologic treatments. Hormonal effects will be assayed in individual, sexually experienced males using an unique experimental protocol that allows sequential blood samples to be obtained from mice during sexual encounters. First, spontaneous LH pulses will be evaluated, then a urine stimulus will be delivered, followed by placement of a female into the cage. Advantages of this paradigm include the abilities to distinguish generalized from specific inhibition of episodic LH release, and to compare directly each male's LH reflexes to pheromones and to a female. Thus, within the context of a novel experimental approach, this proposal offers new insights into the neural control of male's LH secretion and promises to develop a neuroendocrine model of the extrinsic and intrinsic regulation of fertility.
