title: Thinking globally, acting locally: steroid hormone regulation of the dendritic architecture, synaptic connectivity and death of an individual neuron.
abstract: Steroid hormones act via evolutionarily conserved nuclear receptors to regulate neuronal phenotype during development, maturity and disease. Steroid hormones exert 'global' effects in organisms to produce coordinated physiological responses whereas, at the 'local' level, individual neurons can respond to a steroidal signal in highly specific ways. This review focuses on two phenomena-the loss of dendritic processes and the programmed cell death (PCD) of neurons-that can be regulated by steroid hormones (e.g. during sexual differentiation in vertebrates). In insects such as the moth, Manduca sexta, and fruit fly, Drosophila melanogaster, ecdysteroids orchestrate a reorganization of neural circuits during metamorphosis. In Manduca, accessory planta retractor (APR) motoneurons undergo dendritic loss at the end of larval life in response to a rise in 20-hydroxyecdysone (20E). Dendritic regression is associated with a decrease in the strength of monosynaptic inputs, a decrease in the number of contacts from pre-synaptic neurons, and the loss of a behavior mediated by these synapses. The APRs in different abdominal segments undergo segment-specific PCD at pupation and adult emergence that is triggered directly and cell-autonomously by a genomic action of 20E, as demonstrated in cell culture. The post-emergence death of APRs provides a model for steroid-mediated neuroprotection. APR death occurs by autophagy, not apoptosis, and involves caspase activation and the aggregation and ultracondensation of mitochondria. Manduca genes involved in segmental identity, 20E signaling and PCD are being sought by suppressive subtractive hybridization (SSH) and cDNA microarrays. Experiments utilizing Drosophila as a complementary system have been initiated. These insect model systems contribute toward understanding the causes and functional consequences of dendritic loss and neurodegeneration in human neurological disorders.
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007313:Insecta; D008675:Metamorphosis, Biological / Q000502:physiology; D008959:Models, Neurological; D009132:Muscles / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
chemical_list: D012739:Gonadal Steroid Hormones