Novel Exon 1 of the Aromatase Gene Specific for Aromatase Transcripts in Human Brain

Honda, Shin‐ichiro; Harada, N.; Takagi, Yasuyuki

doi:10.1006/bbrc.1994.1163

Cited by 143 publications

(73 citation statements)

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“…In addition, prominent P450arom-I neurons were present in the mPO-AM of the Ad4BP-deficient new-born mice, indicating that the P450arom gene is not regulated by Ad4BP in the brain. Presence of a functional Ad4 site in the upstream of the P450arom gene was confirmed with ovarian granulosa cells (Fitzpatrick and Richards, 1993), whereas no Ad4 site was found in the upstream region of the brain specific first exon of the human P450arom gene (Honda et al, 1994). These observations strongly support that the regulatory mechanism of the P450arom in the brain is distinct from that in the peripheral tissues.…”

Section: Brain P-450arom Under the Control Of A Mechanism Distinct Frmentioning

confidence: 61%

Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice

Shinoda

Lei

Yoshii

et al. 1995

Developmental Dynamics

347

231

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Ad4BP (or SF-1) has been identified as a transcription factor which regulates all the steroidogenic P450 genes in the peripheral organs, and is encoded by the mammalian homologue of Drosophila FTZ-F1 gene. mRNA coding for Ad4BP was detected in the hypothalamus and pituitary of rats by RT-PCR. Immunohistochemical analyses using an antiserum to Ad4BP in the brain and pituitary revealed that the transcription factor is expressed in nuclei of the dorsomedial part of the ventromedial hypothalamus (dmVMH) and in some subpopulation of the adenohypophysial cells. Double immunostaining of the pituitary for Ad4BP and trophic peptide hormones, FSH, TSH, and ACTH, indicated a restricted localization of Ad4BP to the gonadotroph. Disruption of the mouse Ftz-FI gene was clarified to induce severe defects in the organization of the dmVMH and the function of the pituitary gonadotroph. However, some of the dm VMH neurons and pituitary gonadotrophs persisted, which provided a sharp contrast to complete agenesis of the peripheral steroidogenic tissues (adrenal and gonads) in the mutant mouse. Additional abnormalities were seen in the ventrolateral part of VMH and dorsomedial hypothalamic nucleus, both of which do not express Ad4BP but have strong reciprocal fiber-connections with the dmVMH. Aromatase P450-containing cells in the medial preoptico-amygdaloid region, which were devoid of Ad4BP, persisted even in the brain of the gene disrupted mice. The present results clearly showed that the hypothalamic and pituitary Ad4BPs are essential to normal development of the functional VMH and gonadotroph through some mechanism distinct from that in the peripheral steroidogenic tissues. 8 1995 Wiley-Liss, Inc.

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Section: Brain P-450arom Under the Control Of A Mechanism Distinct Frmentioning

confidence: 61%

Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice

Shinoda

Lei

Yoshii

et al. 1995

Developmental Dynamics

347

231

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“…A prominent role for brain aromatase has been established for the control of male sexual behavior in a variety of species [12,22,30,[58][59][60]70,116,258,274,275]. Central aromatization also plays a role in the control of aggressive behaviors [227][228][229]247,258], neuroprotection [10], nociception [43, [83][84][85], the development of sexual preferences [214] and synaptic plasticity [197].…”

Section: The Fast Effects Of Estrogens: Systemic or Central Origin Ofmentioning

confidence: 99%

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

2006

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Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

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“…5 Promoter I.f is expressed in brain tissue. 6,7 Several brain regions make aromatase, 4 and the enzyme is located primarily in neuronal cell bodies and in presynaptic terminals. 2 Aromatase inhibition can reduce axon growth in developing neurons and reduce the number of hippocampal spine synapses.…”

Section: Introductionmentioning

confidence: 99%

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

Garringer

Niyonkuru

McCullough

et al. 2013

Journal of Neurotrauma

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Although experimental traumatic brain injury (TBI) studies support estradiol as a neuroprotectant and potent stimulator of neuroplasticity, clinical studies suggest a negative association between endogenous estradiol profiles and mortality/poor outcomes. However, no studies have evaluated associations with cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450 [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone ratios (E2:T) were measured using CSF and serum samples and compared to healthy controls. Eighteen tagging and four functional single-nucleotide polymorphisms (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF estradiol over time versus controls. CSF testosterone was initially high, but declined over time. E2/T ratios were initially low, compared to controls, but rose over time. Higher mean E2/T ratio in bivariate analysis was associated with lower mortality ( p = 0.019) and better GOS-6 scores ( p = 0.030). rs2470152 influenced CSF E2/T ratio and also serum and CSF testosterone ( p £ 0.05 all comparisons). Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse GOS-6 scores ( p £ 0.05, all comparisons), and those with > 1 risk SNP variant had a higher risk for poor outcome, compared with those with £ 1 risk variant. TBI results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated with better outcome. Further, genetic variation in CYP19A1 influences both hormone dynamics and outcome post-TBI.

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Novel Exon 1 of the Aromatase Gene Specific for Aromatase Transcripts in Human Brain

Cited by 143 publications

References 0 publications

Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice

Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

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