Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain

Cisternas, Carla D.; Tome, Karina; Caeiro, Ximena E.; Dadam, Florencia María; Garcia-Segura, Luis Miguel; Cambiasso, María Julia

doi:10.1016/j.mce.2015.07.027

Cited by 41 publications

(56 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In agreement with previous studies in the anterior amygdala in vivo 7 , male neuronal cultures of E15 CD1 embryos expressed higher levels of Cyp19a1 mRNA (Student’s t-test: p = 0.05; Fig. 1A) and this was also the case for protein expression (Student’s t-test: p = 0.04; Fig.…”

Section: Resultssupporting

confidence: 92%

“…In concordance with previous results we recently demonstrated a sex chromosome-induced difference in aromatase expression in the anterior amygdaloid area and the stria terminalis of the mouse brain as early as embryonic day 16 7 (E16). These and previous findings of higher activity and expression of aromatase in hypothalamic regions of male rat and mouse brain at E16 8–11 are not determined by the prenatal increase in T production by the foetal testis, which in rats occurs at E18.5–19.5 12, 13 and in mice at E17–18 14, 15 .…”

Section: Introductionsupporting

confidence: 92%

“…Therefore, the amygdala has the enzymatic machinery to synthetize DHT from T. In addition, we have shown that the treatment with DHT resulted in an increase in Cyp19a1 mRNA levels in amygdala neuronal cultures originating from E15 female mice 7 . In view of this finding, the same experimental procedure was applied to amygdala neuronal cultures in order to determine the mechanism involved in this regulation.…”

Section: Resultsmentioning

confidence: 86%

“…Our previous study using amygdala neuronal cultures indicates that E2 and DHT regulate aromatase expression through a mechanism controlled by sex chromosome complement. E2 and DHT increase aromatase mRNA levels in cultures of anterior amygdala neurons coming from XX embryos 7 . Since oestrogen (ER) and androgen (AR) receptors are critical for steroid hormone effects during brain development and their expression mostly corresponds to brain regions which express aromatase 25 , brain masculinization requires ERs in some brain regions and AR function in others.…”

Section: Introductionmentioning

confidence: 92%

“…These and previous findings of higher activity and expression of aromatase in hypothalamic regions of male rat and mouse brain at E16 8–11 are not determined by the prenatal increase in T production by the foetal testis, which in rats occurs at E18.5–19.5 12, 13 and in mice at E17–18 14, 15 . Importantly, the use of the “Four Core Genotypes” (FCG) mouse model in our previous study 7 allowed us to establish that sex chromosomes influence aromatase independently of gonadal status. This mouse model combines a spontaneous deletion of the sex determining region Y ( Sry gene) from the Y chromosome (Y − ) with the re-insertion of a functional Sry transgene onto an autosome 16, 17 .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Regulation of aromatase expression in the anterior amygdala of the developing mouse brain depends on ERβ and sex chromosome complement

Cisternas

Zapata

Arévalo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

During development sex differences in aromatase expression in limbic regions of mouse brain depend on sex chromosome factors. Genes on the sex chromosomes may affect the hormonal regulation of aromatase expression and this study was undertaken to explore that possibility. Male E15 anterior amygdala neuronal cultures expressed higher levels of aromatase (mRNA and protein) than female cultures. Furthermore, treatment with oestradiol (E2) or dihydrotestosterone (DHT) increased Cyp19a1 expression and aromatase protein levels only in female neuronal cultures. The effect of E2 on aromatase expression was not imitated by oestrogen receptor (ER) α agonist PPT or the GPER agonist G1, but it was fully reproduced by DPN, a specific ligand of ERβ. By contrast, the effect of DHT on aromatase expression was not blocked by the anti-androgen flutamide, but completely abrogated by the ERβ antagonist PHTPP. Experiments using the four core genotype model showed a sex chromosome effect in ERβ expression (XY > XX) and regulation by E2 or DHT (only XX respond) in amygdala neurons. In conclusion, sex chromosome complement governs the hormonal regulation of aromatase expression through activation of ERβ in developing mouse brain.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Introductionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of aromatase expression in the anterior amygdala of the developing mouse brain depends on ERβ and sex chromosome complement

Cisternas

Zapata

Arévalo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

X-linked histone H3K27 demethylase Kdm6a regulates sexually dimorphic differentiation of hypothalamic neurons

Zapata

Cisternas

Sosa

et al. 2021

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Several X-linked genes are involved in neuronal differentiation and may contribute to the generation of sex dimorphisms in the brain. Previous results showed that XX hypothalamic neurons grow faster, have longer axons, and exhibit higher expression of the neuritogenic gene neurogenin 3 (Ngn3) than XY before perinatal masculinization. Here we evaluated the participation of candidate X-linked genes in the development of these sex differences, focusing mainly on Kdm6a, a gene encoding for an H3K27 demethylase with functions controlling gene expression genome-wide. We established hypothalamic neuronal cultures from wild-type or transgenic Four Core Genotypes mice, a model that allows evaluating the effect of sex chromosomes independently of gonadal type. X-linked genes Kdm6a, Eif2s3x and Ddx3x showed higher expression in XX compared to XY neurons, regardless of gonadal sex. Moreover, Kdm6a expression pattern with higher mRNA levels in XX than XY did not change with age at E14, P0, and P60 in hypothalamus or under 17β-estradiol treatment in culture. Kdm6a pharmacological blockade by GSK-J4 reduced axonal length only in female neurons and decreased the expression of neuritogenic genes Neurod1, Neurod2 and Cdk5r1 in both sexes equally, while a sex-specific effect was observed in Ngn3. Finally, Kdm6a downregulation using siRNA reduced axonal length and Ngn3 expression only in female neurons, abolishing the sex differences observed in control conditions. Altogether, these results point to Kdm6a as a key mediator of the higher axogenesis and Ngn3 expression observed in XX neurons before the critical period of brain masculinization.

show abstract

Non-reproductive Functions of Aromatase in the Central Nervous System Under Physiological and Pathological Conditions

Brocca

Garcia-Segura

2018

Cell Mol Neurobiol

View full text Add to dashboard Cite

The modulation of brain function and behavior by steroid hormones was classically associated with their secretion by peripheral endocrine glands. The discovery that the brain expresses the enzyme aromatase, which produces estradiol from testosterone, expanded this traditional concept. One of the best-studied roles of brain estradiol synthesis is the control of reproductive behavior. In addition, there is increasing evidence that estradiol from neural origin is also involved in a variety of non-reproductive functions. These include the regulation of neurogenesis, neuronal development, synaptic transmission, and plasticity in brain regions not directly related with the control of reproduction. Central aromatase is also involved in the modulation of cognition, mood, and non-reproductive behaviors. Furthermore, under pathological conditions aromatase is upregulated in the central nervous system. This upregulation represents a neuroprotective and likely also a reparative response by increasing local estradiol levels in order to maintain the homeostasis of the neural tissue. In this paper, we review the non-reproductive functions of neural aromatase and neural-derived estradiol under physiological and pathological conditions. We also consider the existence of sex differences in the role of the enzyme in both contexts.

show abstract

Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain

Cited by 41 publications

References 62 publications

Regulation of aromatase expression in the anterior amygdala of the developing mouse brain depends on ERβ and sex chromosome complement

Regulation of aromatase expression in the anterior amygdala of the developing mouse brain depends on ERβ and sex chromosome complement

X-linked histone H3K27 demethylase Kdm6a regulates sexually dimorphic differentiation of hypothalamic neurons

Non-reproductive Functions of Aromatase in the Central Nervous System Under Physiological and Pathological Conditions

Contact Info

Product

Resources

About