Identification and Developmental Changes of Aromatase and Estrogen Receptor Expression in Prepubertal and Pubertal Human Adrenal Tissues

Baquedano, María Sonia; Saraco, Nora; Berensztein, Esperanza; Pepe, Carolina; Bianchini, Michele; Levy, Estrella Mariel; Goñi, Javier; Rivarola, Marco A.; Belgorosky, Alicia

doi:10.1210/jc.2006-2329

Cited by 43 publications

(37 citation statements)

References 35 publications

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“…While such low levels of expression could not significantly affect circulating levels of adrenally sourced corticosteroid, the abundance of MR and GR within hippocampus and cerebellum suggest a paracrine or autocrine mode of action for any steroid synthesised within the CNS. RT-PCR of adrenal cDNA also detected transcription of the aromatase (CYP19) gene, confirming the recent study by Baquedano et al (2007) who detected aromatase mRNA in normal adrenal medulla and zona glomerulosa and confirmed the enzyme's expression by immunohistochemistry.…”

Section: Discussionsupporting

confidence: 85%

The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue

MacKenzie¹,

Dewar²,

Stewart³

et al. 2007

Journal of Endocrinology

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Steroid actions on brain tissue have been implicated in processes such as blood pressure regulation and neurodegeneration, including the progression of Alzheimer's disease (AD). mRNAs from all of the genes required for de novo synthesis from cholesterol of aldosterone and corticosterone (equivalent to cortisol in humans) have been identified in rat brain, together with abundant steroid hormone receptors, but the situation in human brain requires clarification. We used real-time RT-PCR to assess whether transcription of 13 steroid-associated genes occurs in human hippocampus and cerebellum, and to identify whether transcription of these genes is significantly altered in cases of AD. Frozen post-mortem samples of hippocampus and cerebellum from patients with AD (nZ7) and age-matched controls free from neurological disease at the time of death (nZ9) were used. We found all of the genes under investigation to be transcribed within normal and AD hippocampus and cerebellum except for CYP11B1 (11b-hydroxylase), CYP11B2 (aldosterone synthase) and CYP17 (17a-hydroxylase). No significant differences in mRNA levels were observed between the AD tissue and the equivalent control tissue, although significant regional differences in gene transcription were observed between hippocampus and cerebellum in AD and control samples. The absence of key mRNAs from human hippocampus and cerebellum rules out the de novo generation of aldosterone, cortisol or the sex steroids within these regions. However, the pattern of gene expression does suggest that the mineralocorticoid 11-deoxycorticosterone can be generated de novo. There is no evidence of a link between AD and altered steroid biosynthesis within human hippocampus and cerebellum.

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Section: Discussionsupporting

confidence: 85%

The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue

MacKenzie¹,

Dewar²,

Stewart³

et al. 2007

Journal of Endocrinology

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“…This receptor is highly expressed in the ZG and medulla of the human adrenal gland [34], in cultured bovine adrenal medullary cells [35] and in adrenal medulla of GPR30-LacZ reporter mice [36]. In the male and female rats adrenal medulla and cells within the ZG of the adrenal cortex, high levels www.fhc.viamedica.pl of GPR30 mRNA and GPR30-like immunoreactivity were observed [37].…”

Section: Discussionmentioning

confidence: 98%

“…In contrast to animals, numerous data are available on aromatase expression in human adrenals. Aromatase expression has been observed in the human fetal and adult normal adrenal gland [29,34,46]. However, expression of aromatase gene is very high in adrenocortical tumors, especially those secreting estrogens [29,47,48].…”

Section: Discussionmentioning

confidence: 99%

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

Trejter

Jopek

Celichowski

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Adrenocortical activity in various species is sensitive to androgens and estrogens. They may affect adrenal cortex growth and functioning either via central pathways (CRH and ACTH) or directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis. Only limited data on expression of androgen and estrogen receptors in adrenal glands are available. Therefore the present study aimed to characterize, at the level of mRNA, expression of these receptors in specific components of adrenal cortex of intact adult male and female rats. Material and methods. Studies were performed on adult male and female (estrus) Wistar rats. Total RNA was isolated from adrenal zona glomerulosa (ZG) and fasciculate/reticularis (ZF/R). Expression of genes were evaluated by means of Affymetrix ® Rat Gene 1.1 ST Array Strip and QPCR. Results. By means of Affymetrix ® Rat Gene 1.1 ST Array we examined adrenocortical sex differences in the expression of nearly 30,000 genes. All data were analyzed in relation to the adrenals of the male rats. 32 genes were differentially expressed in ZG, and 233 genes in ZF/R. In the ZG expression levels of 24 genes were lower and 8 higher in female rats. The more distinct sex differences were observed in the ZF/R, in which expression levels of 146 genes were lower and 87 genes higher in female rats. Performed analyses did not reveal sex differences in the expression levels of both androgen (AR) and estrogen (ER) receptor genes in the adrenal cortex of male and female rats. Therefore matrix data were validated by QPCR. QPCR revealed higher expression levels of AR gene both in ZG and ZF/R of male than female rats. On the other hand, QPCR did not reveal sex-related differences in the expression levels of ERa, ERb and non-genomic GPR30 (GPER-1) receptor. Of those genes expression levels of ERa genes were the highest. In studied adrenal samples the relative expression of ERa mRNA was higher than ERb mRNA. In adrenals of adult male and female rats expression levels of estrogen-related receptors ERRa and ERRb were similar, and only in the ZF/R of female rats ERRg expression levels were significantly higher than in males. We also analyzed expression profile of three isoforms of steroid 5a-reductase (Srd5a1, Srd5a2 and Srd5a3) and aromatase (Cyp19a1) and expression levels of all these genes were similar in ZG and ZF/R of male and female rats. Conclusions. In contrast to Affymetrix microarray data QPCR revealed higher expression levels of AR gene in adrenal glands of the male rats. In adrenals of both sexes expression levels of ERa, ERb, non-genomic GPR30 (GPER-1), ERRa and ERRb receptors were comparable. The obtained results suggest that acute steroidogenic effect of estrogens on corticosteroid secretion may be mediated by non-genomic GPR30.

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“…Stojković R, et al Age and sex differences in genome damage between prepubertal and adult mice after exposure to ionising radiation Arh Hig Rada Toksikol 2016;67:297-303 Sex-and age-related differences in the effects of ionising radiation are affected by different levels of oestrogen receptors in tissues during prepuberty in comparison with adults, as reported in human adrenal tissue (25). Increased levels of oestrogen two months after exposure to ionising radiation were described in prepubertal mice (5).…”

mentioning

confidence: 94%

Age and sex differences in genome damage between prepubertal and adult mice after exposure to ionising radiation

Stojković

Fučić

Ivanković

et al. 2016

Archives of Industrial Hygiene and Toxicology

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The mechanisms that lead to sex and age differences in biological responses to exposure to ionising radiation and related health risks have still not been investigated to a satisfactory extent. The significance of sex hormones in the aetiology of radiogenic cancer types requires a better understanding of the mechanisms involved, especially during organism development. The aim of this study was to show age and sex differences in genome damage between prepubertal and adult mice after single exposure to gamma radiation. Genome damage was measured 24 h, 48 h, and 72 h after exposure of 3-week and 12-week old BALB/CJ mice to 8 Gy of gamma radiation using an in vivo micronucleus assay. There was a significantly higher genome damage in prepubertal than in adult animals of both sexes for all sampling times. Irradiation caused a higher frequency of micronuclei in males of both age groups. Our study confirms sex differences in the susceptibility to effects of ionising radiation in mice and is the first to show that such a difference occurs already at prepubertal age.

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Identification and Developmental Changes of Aromatase and Estrogen Receptor Expression in Prepubertal and Pubertal Human Adrenal Tissues

Cited by 43 publications

References 35 publications

The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue

The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

Age and sex differences in genome damage between prepubertal and adult mice after exposure to ionising radiation

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