and action in the developing neuron.
In vitro studies using cultured cerebellar slices of newborn rats showed that progesterone promotes dendritic growth and dendritic spine formation of the Purkinje cell (Sakamoto et al., , ; Figure ). A similar result was obtained by in vivo studies (Sakamoto et al., , ). The stimulatory action of progesterone on Purkinje dendrites was completely blocked by a combined administration of the PR antagonist mifepristone (RU486) in vitro (Sakamoto et al., , ). Furthermore, in vivo administration of RU486 during the endogenous peak of progesterone inhibited dendritic growth and dendritic spine formation of the Purkinje cell (Sakamoto et al., , ). Electron microscopic analysis further revealed that progesterone induces an increase in the density of dendritic axospinous synapses on the Purkinje cell (Sakamoto et al., , ; Figure ). In contrast, there was no significant change in the density of dendritic shaft synapses after progesterone administration (Sakamoto et al., , ). The effect of progesterone on Purkinje dendritic spine synapses was also blocked by RU486 (Sakamoto et al., , ). In contrast to progesterone, there was no significant effect of allopregnanolone on Purkinje dendritic growth, spinogenesis, and synaptogenesis (Sakamoto et al., , ). These results indicate that progesterone promotes the dendritic growth, spinogenesis, and synaptogenesis of Purkinje cells during cerebellar development (Figure ). To draw a firm conclusion, however, further study is needed because RU486 is considered to be not a pure PR antagonist, but rather a PR modulator (Ghoumari et al., ).
Progesterone biosynthesis and action in ..
All arthropods periodically molt to replace their exoskeleton (cuticle). Immediately after shedding the old cuticle, the neurohormone bursicon causes the hardening and darkening of the new cuticle. Here we show that bursicon, to our knowledge the first heterodimeric cystine knot hormone found in insects, consists of two proteins encoded by the genes burs and pburs (partner of burs). The pburs/burs heterodimer from Drosophila melanogaster binds with high affinity and specificity to activate the G protein-coupled receptor DLGR2, leading to the stimulation of cAMP signaling in vitro and tanning in neck-ligated blowflies. Native bursicon from Periplaneta americana is also a heterodimer. In D. melanogaster the levels of pburs, burs, and DLGR2 transcripts are increased before ecdysis, consistent with their role in postecdysial cuticle changes. Immunohistochemical analyses in diverse insect species revealed the colocalization of pburs- and burs-immunoreactivity in some of the neurosecretory neurons that also express crustacean cardioactive peptide. Forty-three years after its initial description, the elucidation of the molecular identity of bursicon and the verification of its receptor allow for studies of bursicon actions in regulating cuticle tanning, wing expansion, and as yet unknown functions. Because bursicon subunit genes are homologous to the vertebrate bone morphogenetic protein antagonists, our findings also facilitate investigation on the function of these proteins during vertebrate development.
The discovery that functional bilateral pathways exist between the immune and neuroendocrine systems has been one of the most fascinating developments aiding our understanding of the regulation of the homeostatic balance of living organisms challenged by foreign materials. Physical, emotional and environmental stimuli, including infection, can harm bodily integrity, and a complex network operating at the level of hypothalamus coordinates the appropriate metabolic, behavioral and endocrine changes necessary for the restoration of homeostasis. However, when noxious signals overcome the ability to restore physiological balance in mammalian organisms, one of the final consequence may be an impairment of reproductive processes. Increased production of cytokines, proteins released by activated macrophages and lymphocytes upon presentation of an antigen, represents a central step of the early events of immune activation (the acute-phase response). Apart from the diverse and overlapping activities that these circulating lymphocyte-derived mediators exert on biological functions during the immune response (), a potent action of cytokines on neuronal function, behavior, the neuroendocrine system and metabolism has been demonstrated. Cytokines are systemically produced and may also be synthesized and released directly within the brain to interact with both neurons and glia. The most extensively studied cytokine in the brain, IL-1, is an important neuromodulator exhibiting pleiotropic biological actions and having the capacity to deeply influence neuroendocrine functions. Interestingly, brain production of cytokines is stimulated not only by systemic immune challenge (), but also after exposure to a neurogenic immobilization stress (). These brain-derived cytokines may therefore be part of the stress-related pathways and mediate the information received from the periphery, in particular from circulating immune-related substances. Whether brain-derived IL-1 is involved in the physiologic control of the HPG axis or whether its secretion is activated only in response to stressful stimuli are currently the subject of profound controversies.
CiteSeerX — Neurosteroid Biosynthesis and Action in …
N2 - Probing undiscovered neurosubstances that play important roles in the regulation of cerebellar function is essential for the progress of our understanding of the cerebellum. New findings over the past decade have established that the cerebellum as well as other brain regions synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain are called neurosteroids. Recently the Purkinje cell, a cerebellar neuron, has been identified as a major site for neurosteroid formation in the brain. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar cortical formation occurs. 3α,5α-Tetrahydroprogesterone (allopregnanolone) is metabolized from progesterone in the neonatal cerebellum. Estrogen formation in the Purkinje cell may also occur in the neonate. Subsequently, recent studies on mammals using the Purkinje cell have demonstrated organizing actions of neurosteroids. Both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in Purkinje neurons. Allopregnanolone is also involved in Purkinje and granule cell survival. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to organizing actions of neurosteroids.