Synaptic Aromatase;a Novel Form of Estrogen Delivery

Lehigh University, Bethlehem PA

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Abstract

[unreadable] DESCRIPTION (Provided by applicant): Steroid provision to neural pathways is achieved via endocrine pathways, but also paracrine and autocrine mechanisms within the brain itself. These modes of delivery underlie the considerable influence of steroids like estrogen on vertebrate brain and behavior, including that of songbirds. Using a novel antibody, we have discovered that estrogen can be provided to specific telencephalic neurons via synaptic innervation in the zebra finch (Taeniopygia guttata). This "synaptocrine" mechanism involves the transport of aromatase to synaptic terminals far from their source. This action combines the long-range characteristic of endocrine events with the targeted specificity of axonal innervation. Presynaptic aromatization could dramatically alter the steroidal milieu in the synaptic cleft, thus altering synaptic function. Recent findings that show the rapid modulation of aromatase activity by ionophores and estrogen receptor at post-synaptic densities strongly suggest that presynaptic aromatization is functional. In zebra finches and canaries (Serinus canarius), we will confirm the expression of synaptic aromatase using radioenzymatic assays and immuno-electron microscopy. Second, we will test the differential regulation of synaptosomal and microsomal aromatase, and the association of synaptic aromatization with singing behavior. Finally, we will establish the interaction of synaptic aromatase with estrogen- and androgen receptors using double-label confocal and electron microscopy. Presently, although synaptic aromatase has been documented in several species, including humans, nothing is known about its regulation and function. These studies will describe a mechanism that couples electrical and hormonal signaling, possibly revealing a fundamental and novel characteristic of neuroendocrine function.