ESR2
Estrogen receptor beta (ER-beta) (Nuclear receptor subfamily 3 group A member 2) [ESTRB] [NR3A2]
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Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R2 = 0.46) and females (R2 = 0.30) and AR in males only (R2 = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-à-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R2 = 0.64; females: R2 = 0.58) but not high (males: R2 = 0.0045; females: R2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.
MeSH Terms
- Adolescent
- Aging
- Cerebral Cortex
- Child
- Female
- Gene Expression
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- RNA, Messenger
- Receptors, Androgen
- Receptors, Estrogen
- Receptors, Glucocorticoid
- Receptors, Progesterone
- Sex Factors
- Transcriptome
Changes in estrogen receptor (ER) expression likely underlie differential metabolic effects of estrogen in pre- and postmenopausal women. The aim of the current study was to determine whether ER gene expression in abdominal and femoral subcutaneous adipose tissue (SAT) was associated with age, menopause, or regional adiposity. We studied pre- and post-menopausal (n=23 and 22, respectively; age 35-65y) normal weight (mean±SD; BMI 23.7±2.5kg/m ) women with similar total fat mass. Abdominal and femoral SAT ERα (ESR1) and ERβ (ESR2) mRNA expression was determined by qPCR. Total fat mass did not differ between pre- and postmenopausal women (22.7±5.3vs. 21.7±5.3kg). Compared to premenopausal women, ESR1 and the ratio of ESR1 to ESR2 were lower (p≤0.05) in postmenopausal abdominal and femoral SAT. ESR1 and ESR1:ESR2 were inversely associated with age in abdominal SAT (r=-0.380 and r=-0.463, respectively; p<0.05) and femoral SAT (r=-0.353 and r=-0.472, respectively; p<0.05). ESR2 was not related to age or menopause. The inverse association between ESR1 and age persisted after adjusting for trunk fat mass, estradiol, or leptin. Among healthy pre- and postmenopausal women, increased age was associated with a decreased balance of ERα to ERβ in abdominal and femoral subcutaneous adipose tissue.
MeSH Terms
- Adipose Tissue
- Adiposity
- Adult
- Aged
- Aging
- Estradiol
- Female
- Humans
- Menopause
- Middle Aged
- RNA, Messenger
- Receptors, Estrogen
Keywords
- Adipose tissue
- Aging
- Estrogen receptor gene expression
- Menopause
Estrogens, through their receptors, play an important role in regulation of spermatogenesis. However, the precise role of the estrogen receptors (ESR1 and ESR2) has been difficult to determine as in vivo estradiol treatment would signal through both the ESRs. Hence we had developed in vivo selective ESR agonist administration models in adult male rats to decipher the individual roles of the ESRs. Treatment with both ESR1 and ESR2 agonists decreased sperm counts after 60 days of treatment. The present study aimed to delineate the precise causes of decreased sperm counts following treatment with the two ESR agonists. Treatment with ESR1 agonist causes an arrest in differentiation of round spermatids into elongated spermatids, mainly due to down-regulation of genes involved in spermiogenesis. ESR2 agonist administration reduces sperm counts due to spermiation failure and spermatocyte apoptosis. Spermiation failure observed is due to defects in tubulobulbar complex formation because of decrease in expression of genes involved in actin remodelling. The increase in spermatocyte apoptosis could be due to increase in oxidative stress and decrease in transcripts of anti-apoptotic genes. Our results suggest that the two ESRs regulate distinct aspects of spermatogenesis. ESR1 is mainly involved with regulation of spermiogenesis, while ESR2 regulates spermatocyte apoptosis and spermiation. Activation of estrogen signaling through either of the receptors can affect their respective processes during spermatogenesis and lead to low sperm output. Since many environmental estrogens can bind to the two ESRs with different affinities, these observations can be useful in understanding their potential effects on spermatogenesis.
MeSH Terms
- Aging
- Animals
- Apoptosis
- Cell Count
- Cell Polarity
- Cell Shape
- Cells, Cultured
- Down-Regulation
- Follicle Stimulating Hormone
- Male
- Nitriles
- Oxidative Stress
- Phenols
- Pyrazoles
- Rats
- Real-Time Polymerase Chain Reaction
- Receptors, Estrogen
- Seminiferous Tubules
- Signal Transduction
- Spermatids
- Spermatogenesis
- Testis
- Testosterone
Keywords
- Estrogen receptors
- Germ cell apoptosis
- Spermatogenesis
- Spermiation
- Spermiogenesis
The hypothalamus plays a key role in mediating the effects of estrogen on many physiological functions, including reproduction, metabolism, and thermoregulation. We have previously observed marked estrogen-dependent gene expression changes within the hypothalamus of rhesus macaques during aging, especially in the KNDy neurons of the arcuate-median eminence (ARC-ME) that produce kisspeptin, neurokinin B, and dynorphin A. Little is known, however, about the mechanisms involved in mediating the feedback from estrogen onto these neurons. We used quantitative real-time PCR to profile age- and estrogen-dependent gene expression changes in the rhesus macaque hypothalamus. Our focus was on genes that encode steroid receptors (ESR1, ESR2, PGR, and AR) and on enzymes that contribute to the local synthesis of 17β-estradiol (E2; STS, HSD3B1/2, HSD17B5, and CYP19A). In addition, we used RT(2) Profiler™ PCR Arrays to profile a larger set of genes that are integral to hypothalamic function. KISS1, KISS1R, TAC3, and NPY2R mRNA levels increased in surgically menopausal (ovariectomized) old females relative to age-matched ovariectomized animals that received E2 hormone therapy. In contrast, PGR, HSD17B, GNRH2, SLC6A3, KISS1, TAC3, and NPY2R mRNA levels increased after E2 supplementation. The rhesus macaque ARC-ME expresses many genes that are responsive to changes in circulating estrogen levels, even during old age, and these may contribute to causing the normal and pathophysiological changes that occur during menopause.
MeSH Terms
- Aging
- Animals
- Arcuate Nucleus of Hypothalamus
- Estradiol
- Female
- Gene Expression
- Macaca mulatta
- Menopause
- Ovariectomy
- Receptors, Steroid
Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of ESR2 polymorphisms on age at onset of AD in a multiethnic cohort of women. To determine whether gene variants would affect risk for AD differently in women of different population ancestries. Among 1,686 women participating in the Washington Heights Inwood Columbia Aging Project (WHICAP), association with risk for AD was assessed for 20 ESR2 single-nucleotide polymorphisms (SNPs) using multivariate logistic regression, adjusting for age at time of study enrollment, presence of an APOE ε4 allele, years of education, and body mass index. Increased risk for AD was associated with four ESR2 SNPs in women of predominantly Caucasian AIMS-defined ancestry: rs944045, rs1256062, rs10144225, and rs2274705 (OR range 1.6-1.9, empiric p-value range 0.002-0.004). A separate SNP (rs10137185) was associated with decreased risk for AD in women who identified themselves as Black (OR 0.6, 95% CI = 0.4-0.9). When vascular risk factors were included in the model, a separate SNP (rs1256059) was associated with increased risk for AD in women of admixed/Hispanic ancestry (OR 1.5, 95% CI = 1.1-2.4). ESR2 polymorphisms affect risk for AD in women, and risk alleles vary by AIMs-defined ancestry and self-identified ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid risk factors mediating SNP effect on risk for AD by group.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Cohort Studies
- Estrogen Receptor beta
- Ethnic Groups
- Female
- Genetic Predisposition to Disease
- Genotype
- Humans
- Linkage Disequilibrium
- Polymorphism, Single Nucleotide
- Risk Factors
Keywords
- Alzheimer's disease
- Hispanic
- estrogen receptor 2
- estrogen receptors beta
- genetic association studies
- women
Structural imaging studies suggest gender differences in brain volumes; however, whether hormone treatment (HT) can protect against age-related structural changes remains unknown, and no prior neuroimaging study has investigated potential interactions between HT and estrogen receptor (ESR) polymorphisms. Magnetic resonance imaging was used to measure gray and white matter, hippocampal volume, corpus callosum, cerebrospinal fluid (CSF), total intracranial volume (ICV) and white matter lesions (WML) in 582 non-demented older adults. In multivariable analysis, when compared to women who had never used HT, men and women currently on treatment, but not past users, had significantly smaller ratios of gray matter to ICV and increased atrophy (CSF/ICV ratio). Hippocampal and white matter volume as well as the corpus callosum area were not significantly different across groups. ESR2 variants were not significantly associated with brain measures, but women with the ESR1 rs2234693 C allele had significantly smaller WML. Furthermore this association was modified by HT use. Our results do not support a beneficial effect of HT on brain volumes in older women, but suggest the potential involvement of ESR1 in WML.
MeSH Terms
- Aged
- Aging
- Alleles
- Atrophy
- Brain
- Estradiol
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Estrogen Replacement Therapy
- Female
- Humans
- Magnetic Resonance Imaging
- Male
- Polymorphism, Genetic
- Progesterone
- Sex Characteristics
Keywords
- Estrogen receptor polymorphisms
- Gender differences
- Gray matter
- Hormone treatment
- Imaging
- White matter
- White matter lesions
A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23-2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12-1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05-1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.
MeSH Terms
- Aged
- Aging
- Cognition Disorders
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Female
- Genetic Association Studies
- Genotype
- Humans
- Longitudinal Studies
- Mental Status Schedule
- Neuropsychological Tests
- Polymorphism, Single Nucleotide
- Proportional Hazards Models
- Retrospective Studies
Keywords
- Cognition
- Cognitive decline
- Estrogen receptor
- Estrogen receptor polymorphisms
- Women
Estradiol (E2) is, apart from its role as a reproductive hormone, also important for cardiac function and bone maturation in both genders. It has also been shown to play a role in insulin production, energy expenditure and in inducing lipolysis. The aim of the study was to investigate if low circulating testosterone or E2 levels in combination with variants in the estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) genes were of importance for the risk of type-2 diabetes. The single nucleotide polymorphisms rs2207396 and rs1256049, in ESR1 and ESR2, respectively, were analysed by allele specific PCR in 172 elderly men from the population-based Tromsø study. The results were adjusted for age. In individuals with low total (≤11 nmol/L) or free testosterone (≤0.18 nmol/L) being carriers of the variant A-allele in ESR1 was associated with 7.3 and 15.9 times, respectively, increased odds ratio of being diagnosed with diabetes mellitus type 2 (p = 0.025 and p = 0.018, respectively). Lower concentrations of E2 did not seem to increase the risk of being diagnosed with diabetes. In conclusion, in hypogonadal men, the rs2207396 variant in ESR1 predicts the risk of type 2 diabetes.
MeSH Terms
- Age Distribution
- Aged
- Aged, 80 and over
- Aging
- Alleles
- Cohort Studies
- Confidence Intervals
- Diabetes Mellitus, Type 2
- Estrogen Receptor alpha
- Gene Expression Regulation
- Humans
- Hypogonadism
- Incidence
- Male
- Middle Aged
- Odds Ratio
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
- Predictive Value of Tests
- Retrospective Studies
- Risk Assessment
- Testosterone
Spermatogenesis is a complex and coordinated process leading to the formation of spermatozoa. This event, which is under the control of numerous endocrine and paracrine factors, seems to also be controlled by estrogens which exert their effects via nuclear estrogen receptors (ESRs) ESR1 and ESR2. Estrogens are synthesized by aromatase which is biologically expressed in the rat testis. The objective of our study was to clarify the gene expression patterns of aromatase and ESRs according to age and in the two compartments of the adult rat testis. In the adult, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium, a maximum being observed at stage I. The ESR1 gene is highly expressed in the adult testis and in stages from VIIc-d to XIV. Moreover, both ESR mRNA levels are higher in purified round spermatids than in pachytene spermatocytes, suggesting a putative role of estrogens in the haploid steps of spermatogenesis. The variability of the results in the expression of both ESRs led us to explore the putative presence of variants in the rat testis. Concerning ESR1, we have shown the presence of the full-length form and of one isoform with exon 4 deleted. For ESR2, besides the wild type, three isoforms were observed: one with exon 3 deleted, another with an insertion of 54 nucleotides, and the last one with both modifications. Therefore, the stage-regulated expression of aromatase and ESR1 genes in the rat testis suggests a likely role of estrogens in spermatogenesis.
MeSH Terms
- Aging
- Animals
- Aromatase
- Cell Compartmentation
- Evolution, Molecular
- Gene Expression Regulation, Developmental
- Gene Expression Regulation, Enzymologic
- Male
- Organ Specificity
- Protein Isoforms
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Receptors, Estrogen
- Sertoli Cells
- Testis
Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. A total of 2748 men, aged 40-79 (mean /- sd, 60.2 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
MeSH Terms
- Adult
- Aged
- Aging
- Cohort Studies
- Cross-Sectional Studies
- DNA
- Databases, Genetic
- Europe
- Gene Frequency
- Genotype
- Gonadal Steroid Hormones
- Health Status
- Humans
- Male
- Middle Aged
- Phenotype
- Pituitary Gland
- Polymorphism, Genetic
- Polymorphism, Single Nucleotide
- Prospective Studies
- Sex Hormone-Binding Globulin
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Testis
Steroid hormones play an important role in reproduction and the receptors through which they signal change in a developmental time, follicle stage, and cell-specific manner. Disruption in steroid receptor expression affects follicle formation and differentiation. In this study, using prenatal testosterone (T) and dihydrotestosterone (DHT)-treated female sheep as model systems, we tested the hypothesis that prenatal androgen excess disrupts the developmental ontogeny of ovarian steroid receptor protein expression. Pregnant Suffolk ewes were injected twice weekly with T propionate or DHT propionate (a non-aromatizable androgen) in cottonseed oil from days 30 to 90 of gestation. Changes in ovarian estrogen receptors (ER; ESR1, ESR2), androgen receptor (AR) and progesterone receptor (PGR) proteins were determined at fetal (days 90 and 140), postpubertal (10 months), and adult (21 months; only prenatal T-treated sheep studied) ages by immunohistochemistry. Prenatal T and DHT treatment induced selective increase in AR but not ER or PGR expression in the stroma and granulosa cells of fetal days 90 and 140 ovaries. An increase in ESR1 and decrease in ESR2 immunostaining coupled with increased AR expression were evident in granulosa cells of antral follicles of 10- and 21-month-old prenatal T but not DHT-treated females (analyzed only at 10 months). These findings provide evidence that an early increase in ovarian AR is the first step in the altered ovarian developmental trajectory of prenatal T-treated females, and manifestations of postnatal ovarian dysfunction are likely facilitated via altered equilibrium of antral follicular granulosa cell ER/AR protein expression.
MeSH Terms
- Age Factors
- Aging
- Animals
- Blotting, Western
- Dihydrotestosterone
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Female
- Gestational Age
- Immunohistochemistry
- Ovary
- Pregnancy
- Prenatal Exposure Delayed Effects
- Receptors, Androgen
- Receptors, Progesterone
- Receptors, Steroid
- Sheep
- Testosterone Propionate
Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle-aged and elderly European men. Men 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB, and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 /- 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0 /- 18.9 dB/Mhz, SOS was 1550.2 /- 34.1 m/s, and BMD was 0.542 /- 0.141 g/cm(2). Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta =-0.016, p = -0.005) and homozygotes (beta = -0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR, and ESR1. Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP19A1, as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR, and AR in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.
MeSH Terms
- Aged
- Aging
- Aromatase
- Bone Density
- Calcaneus
- European Continental Ancestry Group
- Genetic Variation
- Genotype
- Gonadal Steroid Hormones
- Humans
- Male
- Middle Aged
- Polymorphism, Genetic
- Repetitive Sequences, Nucleic Acid
- Ultrasonography
In the present study, the authors look at an association of genetic variants within estrogen synthesis and signaling pathways and age at menarche (AAM) in Spanish women. They analyzed 9 polymorphisms in 6 different genes in 714 well-characterized postmenopausal women from Spain. They performed a quantitative trait locus study of these markers individually or in digenic combinations in relation to AAM. None of the studied markers, with the exception of the follicle-stimulating hormone receptor (P = .013), were significantly associated with AAM in the Spanish population, and no marker demonstrated an association of statistical significance after multiple testing corrections (P > .0055). In contrast, linear regression analysis suggests epistatic interactions including ESR1 and ESR2 loci in relation to AAM in the series (P = .003). The results suggest that epistatic interactions of ESR1 and ESR2 alleles could be associated with advancing AAM among Spanish women.
MeSH Terms
- Adolescent
- Age Factors
- Aged
- Aging
- Child
- Epistasis, Genetic
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Estrogens
- Female
- Gene Frequency
- Genotype
- Humans
- Logistic Models
- Menarche
- Middle Aged
- Phenotype
- Polymorphism, Genetic
- Postmenopause
- Signal Transduction
- Spain
To determine whether variants in the estrogen receptors 1 (alpha) and 2 (beta) (ESR1 and ESR2) genes are associated with cognitive impairment in non-demented elderly men and women. Several single nucleotide polymorphisms (SNPs) on ESR1 and ESR2 genes have been associated with a range of hormone sensitive diseases such as breast cancer and osteoporosis. Genetic variations in ESR may also influence cognitive aging but are less studied, especially among men. We studied 2527 participants enrolled in an ongoing prospective study of community-dwelling elders. Four SNPs from ESR1 and four from ESR2 were analyzed. We measured cognitive function with the Modified Mini-Mental Status Examination (3MS) at baseline and biannually; cognitive impairment was defined as a decline of five or more points over 4 years. We calculated odds of developing cognitive impairment across SNPs using gender-stratified logistic regression and adjusted analyses for age, education, baseline 3MS score and in addition for race. One thousand three hundred and forty-three women (mean age 73.4) and 1184 men (mean age 73.7) comprised our cohort. Among women, after multivariate adjustment, two of the ESR1 SNPs (rs8179176, rs9340799) and two of the ESR2 SNPs (rs1256065, rs1256030) were associated with likelihood of developing cognitive impairment, although the association for rs8179176 was of trend level significance. In men, one of the ESR1 SNPs (rs728524) and two of the ESR2 (rs1255998, rs1256030) were associated with cognitive impairment. Further adjustment for race attenuated the results somewhat. There was no association between any ESR SNP and level of bioavailable estradiol but testosterone level did vary among two of the SNPs (p<0.05). We found that among non-demented community elders, several SNPs in the ESR1 and ESR2 genes were associated with risk of developing cognitive impairment. These findings suggest that estrogen receptor genetic variants may play a role in cognitive aging.
MeSH Terms
- Aged
- Aging
- Brain
- Cognition Disorders
- Cohort Studies
- Cytoprotection
- DNA Mutational Analysis
- Estrogen Receptor beta
- Estrogens
- Female
- Genetic Predisposition to Disease
- Genetic Testing
- Genotype
- Humans
- Male
- Polymorphism, Single Nucleotide
- Predictive Value of Tests
- Prognosis
- Prospective Studies
- Receptors, Estrogen
- Risk Factors
Reducing endogenous estrogen leads to increased proliferation of porcine Sertoli cells during the first 2 months of life. The resulting increase in porcine Sertoli cell numbers is maintained through puberty. The reduced estrogen appears to be the direct hormonal mediator because essentially no changes are observed in other hormones. However, the mechanism for this effect on Sertoli cell proliferation is unknown. The objective of these studies was to evaluate estrogen receptors alpha and beta (ESR1 and ESR2) in conjunction with androgen receptor (AR) on Sertoli cells and other testicular cell types, as an initial step toward understanding how reduced estrogen leads to increased Sertoli cell numbers. Testis sections from treated animals (aromatase inhibition to decrease endogenous estrogen beginning at 1 week of age) and from littermate controls treated with vehicle were subjected to immunocytochemical labeling for ESR1, ESR2, and AR. Three observers scored Sertoli cells, interstitial cells, peritubular myoid cells, and germ cells for intensity of labeling (0: absent; 1 : weak; 2 : moderate; or 3 : strong labeling). AR in Sertoli cells was readily detected at 1 week of age, was very faint in 2-month vehicle controls, and labeling appeared to increase in 3-month vehicle controls. AR in Sertoli cells, interstitial cells, and apparently germ cells was increased in treated animals at 2 months of age compared with the vehicle controls. This increase was confirmed in western blots. ESR1 and ESR 2 were clearly present in Sertoli cells from 1-week-old animals; ESR in Sertoli cells generally decreased with age with the decrease more apparent for ESR2. ESR1 in Sertoli cells and peritubular myoid cells exhibited some treatment-related effects but reduction of endogenous estrogen did not appear to affect ESR2 in the boar testis. The observed alterations in AR and ESR1 may mediate the increases in Sertoli cell proliferation following inhibition of endogenous estrogen production or may reflect the altered function of the Sertoli cells and peritubular myoid cells.
MeSH Terms
- Aging
- Animals
- Aromatase Inhibitors
- Blotting, Western
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Estrogens
- Immunohistochemistry
- Letrozole
- Male
- Nitriles
- Receptors, Androgen
- Sertoli Cells
- Swine
- Testis
- Triazoles