Endocrine Disruptors: Focus on the Adrenal Cortex

Pötzl, Benedikt; Kürzinger, Lydia; Stopper, Helga; Fassnacht, Martin; Kurlbaum, Max; Dischinger, Ulrich

doi:10.1055/a-2198-9307

Cited by 3 publications

(3 citation statements)

References 103 publications

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“…The presence and increasing expression of ZIP9 and GPER in the adrenal of immature and mature beavers point to the involvement of fast signaling in the local regulation of these glands, with no exception of their activation by environmental chemicals (Amir et al, 2021). In the latter, steroidogenesis can be modulated mostly negatively and affect other systems which are supervised by mineralocorticoids, glucocorticoids (Pötzl et al, 2024), or linked by androgens and estrogens like gonads (Diamanti-Kandarakis et al, 2009). In humans, congenital estrogen deficiency is associated with an altered lipid profile (Halper et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Is membrane androgen and estrogen receptor signaling imperative in the governing function of the adrenal cortex in the Eurasian beaver (Castor fiber L.)?

Lonc,

Hrabia,

Krakowska

et al. 2024

J Exp Zool Pt A

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There is a need to fully know the physiology of Eurasian beaver due to its essential role in environmental homeostasis. However, a “human factor“ impacts this, including stress conditions and environmental pollution. Adrenal glands protect these all. The regulation of endocrine processes by nonclassical androgen and estrogen signaling, the first and fastest control, is still a matter of research. The specific analyses performed here in mature female and male beaver adrenals contained: anatomical and histological examinations, expression and localization of membrane androgen receptor (zinc transporter, Zinc‐ and Iron‐like protein 9; ZIP9) and membrane estrogen receptor coupled with G protein (GPER), and measurement of zinc (Zn2+) and copper (Ca2+) ion levels and corticosterone levels. We revealed normal anatomical localization, size, and tissue histology in female and male beavers, respectively. Equally, ZIP9 and GPER were localized in the membrane of all adrenal cortex cells. The protein expression of these receptors was higher (p < 0.001) in male than female adrenal cortex cells. Similarly, Zn2+ and Ca2+ ion levels were higher (p < 0.05, p < 0.01) in male than female adrenal cortex. The increased corticosterone levels (p < 0.001) were detected in the adrenal cortex of females when compared to males. The present study is the first to report the presence of nonclassical androgen and estrogen signaling and its possible regulatory function in the adrenal cortex of Eurasian beavers. We assume that this first‐activated and fast‐transmitted regulation can be important in the context of the effect of environmental physical and chemical stressors especially on adrenal cortex cells. The beaver adrenals may constitute an additional supplementary model for searching for universal mechanisms of adrenal cortex physiology and diseases.

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Section: Discussionmentioning

confidence: 99%

Is membrane androgen and estrogen receptor signaling imperative in the governing function of the adrenal cortex in the Eurasian beaver (Castor fiber L.)?

Lonc,

Hrabia,

Krakowska

et al. 2024

J Exp Zool Pt A

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“…In the latter study, the results differed when DDT and DDE were present in the mixture, clearly illustrating the complexity of mixing molecules, even within the same chemical family. Different compounds isolated from our mixture have also been associated with increased testosterone levels in the literature, including PFOA [ 74 ], DEHP [ 75 ] and BDE-47 [ 76 ]. In these studies, as in our study, adrenal participation has not been investigated, although it could have provided valuable information given the role of adrenals in steroid homeostasis [ 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Folliculogenesis and steroidogenesis alterations after chronic exposure to a human-relevant mixture of environmental toxicants spare the ovarian reserve in the rabbit model

El Fouikar,

Van Acker,

Héliès

et al. 2024

J Ovarian Res

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Background Industrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known target of endocrine-disrupting chemicals. This function holds biological processes that are decisive for the fertility of women themselves and for the health of future generations. However, insufficient research has evaluated the risk of combined mixtures on this function. This study aimed to assess the direct impacts of a realistic exposure to eight combined environmental toxicants on the critical process of folliculogenesis. Methods Female rabbits were exposed daily and orally to either a mixture of eight environmental toxicants (F group) or the solvent mixture (NE group, control) from 2 to 19 weeks of age. The doses were computed from previous toxicokinetic data to reproduce steady-state serum concentrations in rabbits in the range of those encountered in pregnant women. Ovarian function was evaluated through macroscopic and histological analysis of the ovaries, serum hormonal assays and analysis of the expression of steroidogenic enzymes. Cellular dynamics in the ovary were further investigated with Ki67 staining and TUNEL assays. Results F rabbits grew similarly as NE rabbits but exhibited higher total and high-density lipoprotein (HDL) cholesterol levels in adulthood. They also presented a significantly elevated serum testosterone concentrations, while estradiol, progesterone, AMH and DHEA levels remained unaffected. The measurement of gonadotropins, androstenedione, pregnenolone and estrone levels yielded values below the limit of quantification. Among the 7 steroidogenic enzymes tested, an isolated higher expression of Cyp19a1 was measured in F rabbits ovaries. Those ovaries presented a significantly greater density/number of antral and atretic follicles and larger antral follicles without any changes in cellular proliferation or DNA fragmentation. No difference was found regarding the count of other follicle stages notably the primordial stage, the corpora lutea or AMH serum levels. Conclusion Folliculogenesis and steroidogenesis seem to be subtly altered by exposure to a human-like mixture of environmental toxicants. The antral follicle growth appears promoted by the mixture of chemicals both in their number and size, potentially explaining the increase in atretic antral follicles. Reassuringly, the ovarian reserve estimated through primordial follicles number/density and AMH is spared from any alteration. The consequences of these changes on fertility and progeny health have yet to be investigated.

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“…The various, sensitive steps in steroidogenesis can most likely be influenced by EDCs ( 18 , 19 ), keeping in mind that even minimal changes in steroid levels in vivo contribute to disrupted endocrine homeostasis. However, dose-response relationships and toxicological targets of EDCs on adrenal steroidogenesis remain still unclear ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Disruptive effects of plasticizers bisphenol A, F, and S on steroidogenesis of adrenocortical cells

Pötzl,

Kürzinger,

Kendl

et al. 2024

Front. Endocrinol.

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IntroductionEndocrine disrupting chemicals (EDCs) are known to interfere with endocrine homeostasis. Their impact on the adrenal cortex and steroidogenesis has not yet been sufficiently elucidated. This applies in particular to the ubiquitously available bisphenols A (BPA), F (BPF), and S (BPS).MethodsNCI-H295R adrenocortical cells were exposed to different concentrations (1nM-1mM) of BPA, BPF, BPS, and an equimolar mixture of them (BPmix). After 72 hours, 15 endogenous steroids were measured using LC-MS/MS. Ratios of substrate and product of CYP-regulated steps were calculated to identify most influenced steps of steroidogenesis. mRNA expression of steroidogenic enzymes was determined by real-time PCR.ResultsCell viability remained unaffected at bisphenol concentrations lower than 250 µM. All tested bisphenols and their combination led to extensive alterations in the quantified steroid levels. The most profound fold changes (FC) in steroid concentrations after exposure to BPA (>10µM) were seen for androstenedione, e.g. a 0.37±0.11-fold decrease at 25µM (p≤0.0001) compared to vehicle-treated controls. For BPF, levels of 17-hydroxyprogesterone were significantly increased by 25µM (FC 2.57±0.49, p≤0.001) and 50µM (FC 2.65±0.61, p≤0.0001). BPS treatment led to a dose-dependent decrease of 11-deoxycorticosterone at >1µM (e.g. FC 0.24±0.14, p≤0.0001 at 10µM). However, when combining all three bisphenols, additive effects were detected: e.g. 11-deoxycortisosterone was decreased at doses >10µM (FC 0.27±0.04, p≤0.0001, at 25µM), whereas 21-deoxycortisol was increased by 2.92±0.20 (p≤0.01) at 10µM, and by 3.21±0.45 (p≤0.001) at 50µM. While every measured androgen (DHEA, DHEAS, androstenedione, testosterone, DHT) was lowered in all experiments, estradiol levels were significantly increased by BPA, BPF, BPS, and BPmix (e.g. FC 3.60±0.54, p≤0.0001 at 100µM BPF). Calculated substrate-product ratios indicated an inhibition of CYP17A1-, and CYP21A2 mediated conversions, whereas CYP11B1 and CYP19A1 showed higher activity in the presence of bisphenols. Based on these findings, most relevant mRNA expression of CYP genes were analysed. mRNA levels of StAR, CYP11B1, and CYP17A1 were significantly increased by BPF, BPS, and BPmix.DiscussionIn cell culture, bisphenols interfere with steroidogenesis at non-cytotoxic levels, leading to compound-specific patterns of significantly altered hormone levels. These results justify and call for additional in-vivo studies to evaluate effects of EDCs on adrenal gland functionality.

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Endocrine Disruptors: Focus on the Adrenal Cortex

Cited by 3 publications

References 103 publications

Is membrane androgen and estrogen receptor signaling imperative in the governing function of the adrenal cortex in the Eurasian beaver (Castor fiber L.)?

Is membrane androgen and estrogen receptor signaling imperative in the governing function of the adrenal cortex in the Eurasian beaver (Castor fiber L.)?

Folliculogenesis and steroidogenesis alterations after chronic exposure to a human-relevant mixture of environmental toxicants spare the ovarian reserve in the rabbit model

Disruptive effects of plasticizers bisphenol A, F, and S on steroidogenesis of adrenocortical cells

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