Estradiol-induced masculinization of the developing preoptic area: Evidence from form to function
AuthorAmateau, Stuart Kevin
AdvisorMcCarthy, Margaret M., 1958-
MetadataShow full item record
AbstractThe developing mammalian brain remains bipotential prior to a restricted perinatal sensitive period during which gonad-specific hormone exposure permanently sexually differentiates physiology and behavior. The rodent provides an excellent model to investigate the complex relationship between developmental steroid hormone exposure, the organization of brain morphology and adult sexual behavior. Although it is clear estrogens mediate sexual differentiation of the brain, the underlying cellular and molecular mechanisms remain elusive. Of particular interest is how steroids exert an organizational effect on developing cells in the preoptic area (POA), resulting in permanent morphological changes that underlie adult sex differences in behavior and physiology. The central importance of glia, in particular astrocytes, to the establishment of synapses in the developing brain is an emerging concept. In light of the effects of estradiol on cellular morphology within the developing arcuate nucleus, we hypothesized that estradiol influences the morphology of both astrocytes and neurons within the developing POA. We demonstrate that estradiol impacts the complexity of astrocytes as well as the density of dendritic spines, the primary loci of excitatory synaptic transmission, within the developing POA. We also identify the participation of prostaglandin-E2 (PGE 2) in cross-talk between the two intimately related cell types. We determine that as early as the day of birth, astrocytes within the POA is sexually dimorphic and this difference is mediated by early exposure to estradiol. Moreover, we detect a region specific mechanism of neuronal spine plasticity in which estradiol induces PGE2 synthesis that in turn increases the density of spine-like processes. We theorized that if PGE2 acts as the cellular messenger of estradiol within the POA during development, then early manipulation of PGE 2 synthesis would ultimately alter adult sexual behavior. We report that briefly preventing prostaglandin synthesis in newborn male rodents with a cyclooxygenase inhibitor completely abolished male sexual behavior. Early exposure to aspirin also impaired adult sexual behavior in the male progeny. Conversely, administering prostaglandin-E2 to females masculinized the POA and resulted in male-typic reproductive behavior. Our current findings emphasize the delicate developmental milieu necessary for organizing the dimorphic neural substrate underlying complicated adult behaviors.
DescriptionUniversity of Maryland, Baltimore. Neuroscience. Ph.D. 2003
Preoptic Area--growth & development