Androgen Receptor Is Dispensable for X-Zone Regression in the Female Adrenal but Regulates Post-Partum Corticosterone Levels and Protects Cortex Integrity

Gannon, Anne-Louise; O’Hara, Laura; Mason, Ian; Jørgensen, Anne; Frederiksen, Hanne; Curley, Martin; Milne, Louise; Smith, Sarah E.; Mitchell, Rod; Smith, Lee B.

doi:10.3389/fendo.2020.599869

Cited by 14 publications

(13 citation statements)

References 46 publications

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“…Gordon et al described for the first time at the end of the 1970s that adrenal glands are the target of estrogens. Since then, other groups have reported the expression of ERα and ERβ (De Cremoux et al, 2008;Caroccia et al, 2016) GPER (Trejter et al, 2015) and AR (Antoniou-Tsigkos et al, 2000;Trejter et al, 2015;Gannon et al, 2020) in the adrenal glands. We have demonstrated here that GPER is the highest receptor expressed in the adrenal glands.…”

Section: Discussionmentioning

confidence: 98%

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

et al. 2022

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Sex steroid hormones, such as androgens and estrogens, are known to exert organizational action at perinatal periods and activational effects during adulthood on the brain and peripheral tissues. These organizational effects are essential for the establishment of biological axes responsible for regulating behaviors, such as reproduction, stress, and emotional responses. Estradiol (E2), testosterone, and their metabolites exert their biological action through genomic and non-genomic mechanisms, bounding to canonical receptors, such as estrogen receptor (ER)α, ERβ, and androgen receptor (AR) or membrane receptors, such as the G protein-coupled estrogen receptor (GPER), respectively. Expression of ERs and AR was found to be different between males and females both in the brain and peripheral tissues, suggesting a sex-dependent regulation of their expression and function. Therefore, studying the ERs and AR distribution and expression levels is key to understand the central and peripheral role of sex steroids in the establishment of sex-specific behaviors in males and females. We investigated the organizational effects of estrogens and androgens in the pituitary and adrenal glands of adult male and female rats. For this, selective blockade of AR with flutamide or 5α-reductase with finasteride or aromatase with letrozole during the first 5 days of life has been performed in male and female pups and then quantification of ERs and AR expression in both glands has been carried out in adulthood. Data show that inhibition of dihydrotestosterone (DHT) and E2 production during the first five postnatal days mainly decreases the ER expression in male to female values and AR expression in female to male levels in the pituitary gland and increases AR expression in female to male levels in the adrenal gland. In contrast, blocking the action of androgens differentially modulates the ERs in males and females and decreases AR in both males and females in both glands. Altogether, the results suggest that neonatal modifications of the androgen and estrogen pathways can potentially lead to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes.

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Section: Discussionmentioning

confidence: 98%

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

et al. 2022

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“…119 Androgen administration, such as androstenedione, will result in the rapid disappearance of the X-zone in female mice, and removing androgens with ovariectomy will prolong the persistence of the X-zone in female mice. [121][122][123][124] While the function of the X-zone is unknown, its normal development and regression are mediated by a variety of factors, including sex steroid hormones, luteinizing hormones, and thyroid hormones. 118 This is the first known study in which exposure to ILs has been linked to this type of lesion in the adrenal gland.…”

Section: Discussionmentioning

confidence: 99%

NTP Technical Report on the Toxicity Studies of Select Ionic Liquids (1‑Ethyl‑3‑Methylimidazolium Chloride, 1‑Butyl‑3‑Methylimidazolium Chloride, 1‑Butyl‑1‑Methylpyrrolidinium Chloride, and N‑Butylpyridinium Chloride) Administered in Drinking Water to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats and B6C3F1/N Mice

2022

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“…Power calculations based on previous cell quantitation experiments determined that a sample size of 3 is appropriate for quantitative end points for cell counting and immunohistochemistry [ 55 ]. Statistical analysis is performed via GraphPad Prism (version 8; GraphPad Software Inc., San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

Gannon

Darbey

Chensee

et al. 2022

IJMS

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Glucocorticoids are steroids involved in key physiological processes such as development, metabolism, inflammatory and stress responses and are mostly used exogenously as medications to treat various inflammation-based conditions. They act via the glucocorticoid receptor (GR) expressed in most cells. Exogenous glucocorticoids can negatively impact the function of the Leydig cells in the testis, leading to decreased androgen production. However, endogenous glucocorticoids are produced by the adrenal and within the testis, but whether their action on GR in Leydig cells regulates steroidogenesis is unknown. This study aimed to define the role of endogenous GR signalling in adult Leydig cells. We developed and compared two models; an inducible Cre transgene driven by expression of the Cyp17a1 steroidogenic gene (Cyp17-iCre) that depletes GR during development and a viral vector-driven Cre (AAV9-Cre) to deplete GR in adulthood. The delivery of AAV9-Cre ablated GR in adult mouse Leydig cells depleted Leydig cell GR more efficiently than the Cyp17-iCre model. Importantly, adult depletion of GR in Leydig cells caused reduced expression of luteinising hormone receptor (Lhcgr) and of steroidogenic enzymes required for normal androgen production. These findings reveal that Leydig cell GR signalling plays a physiological role in the testis and highlight that a normal balance of glucocorticoid activity in the testis is important for steroidogenesis.

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Androgen Receptor Is Dispensable for X-Zone Regression in the Female Adrenal but Regulates Post-Partum Corticosterone Levels and Protects Cortex Integrity

Cited by 14 publications

References 46 publications

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function

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