scholarly journals Rapid Control of Brain Aromatase Activity by Glutamatergic Inputs

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Jacques Balthazart ◽  
Michelle Baillien ◽  
Gregory F. Ball

Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on brain function. Such changes in aromatase activity and hence in local estrogen concentrations could rapidly modulate behavioral responses. We show here that there is a very rapid (within minutes) decrease in aromatase activity in quail hypothalamic explants exposed to treatments affecting intracellular Ca2+ concentrations, such as the addition of glutamate agonists (kainate, α-amino-3-hydroxymethyl-4-isoxazole propionic acid, and, to a much lesser extent, N-methyl-d-aspartate), but not of γ-aminobutyric acid. The kainate effects, which reduce aromatase activity by 25–50%, are observed within 5 min, are completely blocked in explants exposed to specific kainate antagonists (6-cyano-7-nitroquinoxaline-2,3-dione disodium or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and are also rapidly reversible when effectors are washed out. Together, these data support the idea that the synthesis of estrogen can be rapidly regulated in the brain, thus producing rapid changes in local estrogen bioavailability that could rapidly modify brain function with a time course similar to what has previously been described for neurotransmitters and neuromodulators.

2014 ◽  
Vol 73 (4) ◽  
pp. 477-489 ◽  
Author(s):  
Elaine Patterson ◽  
John F. Cryan ◽  
Gerald F. Fitzgerald ◽  
R. Paul Ross ◽  
Timothy G. Dinan ◽  
...  

A healthy gut microbiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or ‘pharmabiotics’. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gut microbiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain–gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gut microbiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.


2019 ◽  
Vol 3 ◽  
pp. 239821281985824 ◽  
Author(s):  
Trevor G Smart ◽  
F Anne Stephenson

γ-aminobutyric acid has become one of the most widely known neurotransmitter molecules in the brain over the last 50 years, recognised for its pivotal role in inhibiting neural excitability. It emerged from studies of crustacean muscle and neurons before its significance to the mammalian nervous system was appreciated. Now, after five decades of investigation, we know that most neurons are γ-aminobutyric-acid-sensitive, it is a cornerstone of neural physiology and dysfunction to γ-aminobutyric acid signalling is increasingly documented in a range of neurological diseases. In this review, we briefly chart the neurodevelopment of γ-aminobutyric acid and its two major receptor subtypes: the γ-aminobutyric acidA and γ-aminobutyric acidB receptors, starting from the humble invertebrate origins of being an ‘interesting molecule’ acting at a single γ-aminobutyric acid receptor type, to one of the brain’s most important neurochemical components and vital drug targets for major therapeutic classes of drugs. We document the period of molecular cloning and the explosive influence this had on the field of neuroscience and pharmacology up to the present day and the production of atomic γ-aminobutyric acidA and γ-aminobutyric acidB receptor structures. γ-Aminobutyric acid is no longer a humble molecule but the instigator of rich and powerful signalling processes that are absolutely vital for healthy brain function.


Behaviour ◽  
1996 ◽  
Vol 133 (3-4) ◽  
pp. 199-219 ◽  
Author(s):  
R.E. Hutchison ◽  
G. Opromolla ◽  
J.B. Hutchison

AbstractIn paired ring doves, Streptopelia risoria, male and female reproductive behaviour undergoes a series of synchronised transitions. The duration of each phase depends on the reproductive development of the pair. This study examines the effect of the environment in which behaviour is shown on both oestrogen-dependent courtship transitions and formation of oestrogen in the brain. The structuring of the cage environment had an immediate effect on transitions in male courtship behaviour. Males which were tested with females in a cage environment with a perch and a nest bowl (complex cage) displayed significantly less aggressive courtship and more nest-orientated behaviour than males tested with females in a cage environment without perch or nest bowl (simple cage). The response of males, which showed aggressive and nest-orientated courtship behaviour, to reproductively advanced females (abdominal length 1.4-1.6 cm) about to lay eggs or females in earlier stages of reproductive development (abdominal length 0.8-1.1 cm) did not differ initially. On the eighth day of 15-min daily tests, there was, however, an increase in aggressive courtship to females with smaller abdomens. This result suggests that male aggressiveness is more likely when the male and female reproductive cycles are not synchronised. We also tested whether environmental factors and the male's hormonal condition, which affect male courtship interactions, influence the formation of behaviourally effective oestrogen by aromatisation of testosterone in the brain. The aromatase activity was measured in the preoptic and anterior hypothalamic areas in relation to the time spent in interaction with females each day. Both intact and castrated males which interacted intermittently (15 min each day for 9 days) had higher preoptic aromatase activity than males which interacted continuously with females. The males which had high brain aromatase activity and had interacted intermittently with females were considered to represent the initial stages of the cycle. We conclude that cage environment and female reproductive condition influence the course of courtship interactions. Oestrogen formation in the male brain is affected by the type of interaction.


2010 ◽  
Vol 85 (3) ◽  
pp. 339-344 ◽  
Author(s):  
C. Boulange-Lecomte ◽  
P. Geraudie ◽  
J. Forget-Leray ◽  
M. Gerbron ◽  
C. Minier

AbstractThe tapeworm Ligulaintestinalis commonly infests roach (Rutilusrutilus) and is responsible for the inhibition of gonad development. In order to better understand the effect of the plerocercoid on fish physiology, and to discriminate parasitization effects from those of endocrine-disrupting compounds (EDC), Cyp19b and Cyp19a aromatase expression was investigated by real-time quantitative polymerase chain reaction (PCR) in brain and gonads of ligulosed roach, caught from a reference site. Data were compared to reproductive and endocrine endpoints previously reported in a larger cohort study (including the sampled population of the present one), such as gonadosomatic index, Fulton index, gonadal histology, plasma sex steroid levels and brain aromatase activity. A decrease in Cyp19b expression in the brain of infected fish was demonstrated, in agreement with the reduction of aromatase activity previously described. In contrast, Cyp19a expression in the gonads appeared to be enhanced in ligulosed fish, in accordance with the presence of immature but differentiated sexual tissues. Together these results show that: (1) L. intestinalis infestation results in an alteration of aromatase expression which, in particular, may have profound effects on the fish brain; and (2) L. intestinalis infection must be considered as a major confounding factor in ecotoxicological studies using aromatase expression as an EDC biomarker. Moreover, the concordance between activity and expression – investigated for the first time in the same population – gives a functional relevance to the transcript aromatase dosage in the brain. Finally, quantitative PCR was confirmed as a sensitive approach, enabling aromatase status to be defined in the poorly developed gonads of ligulosed individuals.


1971 ◽  
Vol 49 (9) ◽  
pp. 833-840 ◽  
Author(s):  
Crystal A. Leslie ◽  
Zehava Gottesfeld ◽  
K. A. C. Elliott

We have examined the effects of a subanesthetic dose of ethanol on the entry into the brains of rats of three 14C-labelled substances which are known to affect brain function. All substances were given intraperitoneally. When ethanol was given the concentration of pentobarbital in the brain reached and was maintained at a higher level than without ethanol. The barbiturate entered the brain and became distributed between plasma, red cells, and brain extremely rapidly in the presence or absence of ethanol. Administration of ethanol decreased the rate of breakdown of pentobarbital, so that higher levels of unchanged pentobarbital were maintained in blood, liver, and brain. Breakdown of the barbiturate occurred rapidly in liver but almost no radioactive breakdown products entered or were formed in the brain. Thiamine entered the brain sparingly but, after 60 min, the ratio of radioactivity per gram of brain to that per milliliter of plasma became considerably greater with ethanol than without. In the absence or presence of ethanol this ratio increased with time due to a rapid disappearance of radioactivity from the plasma while radioactivity in the brain tended to increase slightly. In the presence of ethanol the rate of disappearance from the plasma increased, presumably due to increased uptake and metabolism of thiamine by other tissues. Urinary excretion of radioactivity decreased. Injected γ-aminobutyric acid (GABA), entered the brain very sparingly and much of what entered was metabolized. Ethanol had no effect on the endogenous GABA concentration in the brain nor on the entry or metabolism of injected GABA.


2001 ◽  
Vol 79 (1-5) ◽  
pp. 261-277 ◽  
Author(s):  
Jacques Balthazart ◽  
Michelle Baillien ◽  
Gregory F Ball

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 207-213 ◽  
Author(s):  
J. W. Gatson ◽  
J. W. Simpkins ◽  
K. D. Yi ◽  
A. H. Idris ◽  
J. P. Minei ◽  
...  

Abstract After traumatic brain injury (TBI), a progressive injury and death of neurons and glia leads to decreased brain function. Endogenous and exogenous estrogens may protect these vulnerable cells. In this study, we hypothesized that increased pressure leads to an increase in aromatase expression and estrogen production in astrocytes. In this study, we subjected rat glioma (C6) cells and primary cortical astrocytes to increased pressure (25 mm Hg) for 1, 3, 6, 12, 24, 48, and 72 h. Total aromatase protein and RNA levels were measured using Western analysis and RT-PCR, respectively. In addition, we measured aromatase activity by assaying estrone levels after administration of its precursor, androstenedione. We found that increased pressure applied to the C6 cells and primary cortical astrocytes resulted in a significant increase in both aromatase RNA and protein. To extend these findings, we also analyzed aromatase activity in the primary astrocytes during increased pressure. We found that increased pressure resulted in a significant (P < 0.01) increase in the conversion of androstenedione to estrone. In conclusion, we propose that after TBI, astrocytes sense increased pressure, leading to an increase in aromatase production and activity in the brain. These results may suggest mechanisms of brain estrogen production after increases in pressure as seen in TBI patients.


2017 ◽  
Vol 29 (11) ◽  
pp. e12542 ◽  
Author(s):  
C. de Bournonville ◽  
G. F. Ball ◽  
J. Balthazart ◽  
C. A. Cornil

Author(s):  
Thierry D. Charlier ◽  
Charlotte A. Cornil ◽  
Gregory F. Ball ◽  
Jacques Balthazart

2000 ◽  
Vol 25 (1) ◽  
pp. 35-42 ◽  
Author(s):  
SE Bulun ◽  
KM Zeitoun ◽  
K Takayama ◽  
H Sasano

Conversion of C(19) steroids to estrogens is catalyzed by aromatase in human ovary, placenta and extraglandular tissues such as adipose tissue, skin and the brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by prostaglandin E(2) (PGE(2)).( )This results in local production of estrogen, which induces PGE(2) formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE(2 )in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.


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