Neurochemical Characterization of Neurons Expressing Estrogen Receptor β in the Hypothalamic Nuclei of Rats Using in Situ Hybridization and Immunofluorescence

Kanaya, Moeko; Higo, Shimpei; Ozawa, Hitoshi

doi:10.3390/ijms21010115

Cited by 20 publications

(27 citation statements)

References 70 publications

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“…Importantly, the PVN contains the key enzymes needed for metabolism of androgens to ER ligands including aromatase, 5α-reductase, 17β-HSD, 3α-HSD, and cytochrome p450 7b (CYP7B) [93,187]. ERβ may also directly regulate HPA axis activation, as neuropeptideexpressing PVN neurons known to modulate HPA activity co-express ERβ [171,188] [171,185,188,189]. Alternatively, the BST also contains high levels of ERβ and might be a key site for ERβ regulation of the HPA axis based on its known role in modulating HPA axis tone [3,186].…”

Section: Anatomical Sites Of Action For Erβ Effects On the Hpa Axis Amentioning

confidence: 99%

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Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

et al. 2020

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Estradiol and testosterone are powerful steroid hormones that impact brain function in numerous ways. During development, these hormones can act to program the adult brain in a male or female direction. During adulthood, gonadal steroid hormones can activate or inhibit brain regions to modulate adult functions. Sex differences in behavioral and neuroendocrine (i.e., hypothalamic pituitary adrenal (HPA) axis) responses to stress arise as a result of these organizational and activational actions. The sex differences that are present in the HPA and behavioral responses to stress are particularly important considering their role in maintaining homeostasis. Furthermore, dysregulation of these systems can underlie the sex biases in risk for complex, stress-related diseases that are found in humans. Although many studies have explored the role of estrogen and estrogen receptors in mediating sex differences in stress-related behaviors and HPA function, much less consideration has been given to the role of androgens. While circulating androgens can act by binding and activating androgen receptors, they can also act by metabolism to estrogenic molecules to impact estrogen signaling in the brain and periphery. This review focuses on androgens as an important hormone for modulating the HPA axis and behaviors throughout life and for setting up sex differences in key stress regulatory systems that could impact risk for disease in adulthood. In particular, impacts of androgens on neuropeptide systems known to play key roles in HPA and behavioral responses to stress (corticotropin-releasing factor, vasopressin, and oxytocin) are discussed. A greater knowledge of androgen action in the brain is key to understanding the neurobiology of stress in both sexes.

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Section: Anatomical Sites Of Action For Erβ Effects On the Hpa Axis Amentioning

confidence: 99%

“…Since AR is largely absent in AVP neurons of the PVN, it has been proposed that androgens might act remotely in regions such as the BST to regulate AVP in the rat PVN [149,150,235]. However, AVP neurons in the PVN co-express ERβ indicating that androgen metabolites can directly act on these neurons [189,236,237].…”

Section: Arginine Vasopressinmentioning

confidence: 99%

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

et al. 2020

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“…The kisspeptin neurons in the anteroventral periventicular (AVPV) nucleus of the hypothalamus are believed to mediate positive feedback of estrogen signaling [ 136 ]. Kisspeptin neurons in the AVPV nucleus of the hypothalamus express high levels of estrogen receptor ESR2 [ 137 ]. It is not clear yet, but ESR2 along with ESR1 is implicated in regulation of GnRH through KISS signaling from AVPV nucleus of hypothalamus [ 138 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Heifer Traits Identified Reproductive Pathways in Bos indicus Cattle

Tahir

Porto-Neto

Gondro

et al. 2021

Genes

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Fertility traits measured early in life define the reproductive potential of heifers. Knowledge of genetics and biology can help devise genomic selection methods to improve heifer fertility. In this study, we used ~2400 Brahman cattle to perform GWAS and multi-trait meta-analysis to determine genomic regions associated with heifer fertility. Heifer traits measured were pregnancy at first mating opportunity (PREG1, a binary trait), first conception score (FCS, score 1 to 3) and rebreeding score (REB, score 1 to 3.5). The heritability estimates were 0.17 (0.03) for PREG1, 0.11 (0.05) for FCS and 0.28 (0.05) for REB. The three traits were highly genetically correlated (0.75–0.83) as expected. Meta-analysis was performed using SNP effects estimated for each of the three traits, adjusted for standard error. We identified 1359 significant SNPs (p-value < 9.9 × 10−6 at FDR < 0.0001) in the multi-trait meta-analysis. Genomic regions of 0.5 Mb around each significant SNP from the meta-analysis were annotated to create a list of 2560 positional candidate genes. The most significant SNP was in the vicinity of a genomic region on chromosome 8, encompassing the genes SLC44A1, FSD1L, FKTN, TAL2 and TMEM38B. The genomic region in humans that contains homologs of these genes is associated with age at puberty in girls. Top significant SNPs pointed to additional fertility-related genes, again within a 0.5 Mb region, including ESR2, ITPR1, GNG2, RGS9BP, ANKRD27, TDRD12, GRM1, MTHFD1, PTGDR and NTNG1. Functional pathway enrichment analysis resulted in many positional candidate genes relating to known fertility pathways, including GnRH signaling, estrogen signaling, progesterone mediated oocyte maturation, cAMP signaling, calcium signaling, glutamatergic signaling, focal adhesion, PI3K-AKT signaling and ovarian steroidogenesis pathway. The comparison of results from this study with previous transcriptomics and proteomics studies on puberty of the same cattle breed (Brahman) but in a different population identified 392 genes in common from which some genes—BRAF, GABRA2, GABR1B, GAD1, FSHR, CNGA3, PDE10A, SNAP25, ESR2, GRIA2, ORAI1, EGFR, CHRNA5, VDAC2, ACVR2B, ORAI3, CYP11A1, GRIN2A, ATP2B3, CAMK2A, PLA2G, CAMK2D and MAPK3—are also part of the above-mentioned pathways. The biological functions of the positional candidate genes and their annotation to known pathways allowed integrating the results into a bigger picture of molecular mechanisms related to puberty in the hypothalamus–pituitary–ovarian axis. A reasonable number of genes, common between previous puberty studies and this study on early reproductive traits, corroborates the proposed molecular mechanisms. This study identified the polymorphism associated with early reproductive traits, and candidate genes that provided a visualization of the proposed mechanisms, coordinating the hypothalamic, pituitary, and ovarian functions for reproductive performance in Brahman cattle.

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“…Levels of Esr2, the gene that encodes ERβ, were assessed using RNAscope fluorescent in situ hybridization (FISH). The Esr2 probe (ACD, catalog #317161) was verified in silico by ACD and recently by Kanaya et al 37 . Additionally, the probe was further verified with the positive probe (PPIB, provided by ACD), and absence of signal with the negative probe (provided by ACD) as well as in slices where the Esr2 probe was excluded.…”

Section: Fluorescent In Situ Hybridization With Rnascopementioning

confidence: 95%

“…Therefore, the rapid increase in endogenous estrogens at pubertal onset could influence ERβ expression in the mPFC, a region we have previously shown is sensitive to these hormones during this time 2 Currently, there is no validated antibody that binds to ERβ using immunohistochemistry in perfused tissues 36 . The newer technological method RNAscope, however, has been employed to visualize Esr2, ERβ mRNA, in the rodent brain 37 . Here we aimed to quantify levels of Esr2 in female adolescent and adult rats, with particular emphasis on the effects of pubertal onset on the amount Esr2.…”

Section: Introductionmentioning

confidence: 99%

Impact of pubertal onset on region-specificEsr2expression

Drzewiecki

Sellinger

Juraska

2021

Preprint

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In female rats, pubertal onset is associated with maturation of the medial prefrontal cortex (mPFC) and mPFC-mediated behaviors. These behavioral and anatomical changes are likely due to effects of estrogen at the nuclear estrogen receptor beta (ERβ), which is expressed at higher levels than the estrogen receptor alpha (ERα) isoform in the adult mPFC. Researchers have previously quantified ERβ protein and Esr2 RNA in rodents during early postnatal development and adulthood, but an adolescent-specific trajectory of this receptor in the mPFC has not been documented. Given that levels of Esr2 can fluctuate in the presence or absence of estrogens, puberty and the subsequent rise in gonadal hormones could influence ERβ expression in the adolescent brain. To further explore this, we used RNAscope to quantify the amount of Esr2 mRNA in pre-pubertal adolescent, recently post-pubertal adolescent, and adult female rats. We show here that Esr2 expression decreases significantly in the mPFC, striatum and motor cortex between pre-pubertal adolescence and adulthood. In the mPFC, this decrease occurs rapidly at pubertal onset, with no significant decrease in Esr2 levels between the recently post-pubertal and adult cohort. In contrast in the striatum and motor cortex, there were no significant differences in the amount of Esr2 between pre- and post-pubertal females. Insofar as the amount of Esr2 is proportional to functional ERβ, these results suggest ERβ decreases in a region-specific pattern in response to pubertal onset and highlight a role for this receptor in the maturational events that occur in the female rat mPFC at puberty.

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Neurochemical Characterization of Neurons Expressing Estrogen Receptor β in the Hypothalamic Nuclei of Rats Using in Situ Hybridization and Immunofluorescence

Cited by 20 publications

References 70 publications

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

Meta-Analysis of Heifer Traits Identified Reproductive Pathways in Bos indicus Cattle

Impact of pubertal onset on region-specificEsr2expression

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