The long term goal of this proposal is to understand how brain structures that regulate reproduction, change as a function of reproductive status. Specifically, I propose understanding the cellular and molecular effects that extrinsic, environmental factors have on fertility. Reproduction is ultimately controlled by gonadotropin releasing-hormone-1 (GnRH1) via the hypothalamic-pituitary-gonadal (HPG) axis. GnRH1 is released in pulses at the median eminence where it stimulates the pituitary to secrete circulating luteinizing hormone (LH). Elevated LH then signals the gonads which mature and upregulate androgen synthesis. In the teleost fish, Astatotilapia burtoni, fertility is controlled by social status: dominant territorial males (T) are fertile and subordinate non-territorial males (NT) are not. Social ascent causes GnRH1 neurons to increase in soma size (~8x) and secrete elevated levels of GnRH1, but nothing is known about cellular and molecular mechanisms mediating this change. Here I propose experiments that will elucidate social status-dependent structural changes in GnRH1 neurons. Because changes in dendritic arbors have been shown to alter cell activity, I will characterize the anatomical differences in GnRH1 neurons between T and NT males by using intracellular labeling techniques and confocal microscopy to quantify the degree of dendritic arborization. Moreover, because fertile males show increases in GnRH1 release, which is only effective when released in pulses, the GnRH1 neuron network connections may differ between T and NT males possibly via electrical synapses. Therefore, I will test whether gap junctions are expressed in GnRH1 neurons and serve to connect these cells in fertile animals. Lastly, because increased excitatory input may underlie the activation of GnRH1 neurons during the NT male to T male transition, I will quantify GnRH1 neuron spine density (the locus of excitatory input) to discover whether excitatory synaptic input is also regulated by reproductive status. The HPG axis is highly conserved in all vertebrates and any information about the mechanisms of activation will likely apply to humans. Environment signals such as nutrition, light, stressors, etc., have been shown to modulate the hypothalamic signaling network that regulates reproductive maturation in humans. Indeed, increased incidence in sexual precocity has become a health concern worldwide because patients are more likely to develop major psychopathologies. Understanding not only the neural basis of reproductive onset, but also how these mechanisms are affected by the social and physical environment could be valuable for developing therapies, addressing issues pertinent to health and to the mission of the NIH. ? ? ? ? ?
