The Pathological Mechanisms of Estrogen-Induced Cholestasis: Current Perspectives

Zu, Yue; Yang, Jinyu; Zhang, Chengliang; Liu, Dong

doi:10.3389/fphar.2021.761255

Cited by 30 publications

(13 citation statements)

References 95 publications

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“…It is possible that the use of exogenous gonadotropins during ovulation promotion causes multiple follicles to develop, resulting in elevated estrogen levels in patients with moderate‐to‐severe OHSS, which leads to a significant increase in inflammatory cell‐related factors in the body. Because the liver is a key immunologic organ, a significant increase in estradiol levels can further upset the body's proinflammatory cytokine balance and injure the liver by increasing the expression of inflammatory chemokines 19,20 . In contrast, the use of high‐dose progesterone luteal support after embryo transfer in patients increases progestogen levels, but there is no significant difference in progesterone levels between the two groups, considering that the combined effect of high estrogen levels and progesterone may lead to impairment of multiple metabolic pathways in the liver 21 .…”

Section: Discussionmentioning

confidence: 99%

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications

Liu

et al. 2023

Intl J Gynecology & Obste

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ObjectivesTo explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset.MethodsThis was a single‐center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three‐degree, five‐level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate‐to‐severe OHSS were divided into two groups. A control group included 3427 (96.54%) non‐OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores.ResultsThere was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P < 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P < 0.05).ConclusionIn patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

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Section: Discussionmentioning

confidence: 99%

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications

Liu

et al. 2023

Intl J Gynecology & Obste

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“…The risk is markedly greater with oral treatment because the intestinal absorption is rapid and yields high concentrations of hormone in the portal circulation[ 32 ]. Moreover, estrogens can cause a decrease in bile flow leading to intrahepatic cholestasis with pruritus and jaundice[ 33 ]. They may also be involved in the occurrence of nodular hyperplasia and hepatic benign and malignant tumors after long-term use, although the relevant evidence is not strong[ 34 ].…”

Section: Liver Function In Transgender Femalesmentioning

confidence: 99%

Liver function in transgender persons: Challenges in the COVID-19 era

Milionis¹,

Ilias²,

Koukkou³

2023

World J Clin Cases

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Transgender persons constitute a non-negligible percentage of the general population. Physical gender-transitioning in trans persons is mainly achieved with hormonal cross-sex therapy and sex reassignment surgeries that aim to align bodily appearance with gender identity. Hormonal treatment acts via suppressing the secretion of the endogenous sex hormones and replacing them with the hormones of the desired sex. The administration of testosterone is the typical masculinizing treatment in trans men, whilst trans women are routinely treated with estradiol agents in combination with anti-androgens or gonadotrophin-releasing hormone agonists if testes are present. Exogenous androgenic steroids, estradiol agents, and anti-androgens have been implicated in a series of hepatotoxic effects. Thus, liver integrity is a major concern with the long-term administration of cross-sex therapy. Hepatic tissue is susceptible to coronavirus disease 19 (COVID-19) through various pathophysiological mechanisms. Special consideration should be paid to minimize the risk of hepatic damage from the potential cumulative effect of COVID-19 and gender-affirming treatment in transgender patients. Appropriate care is significant, with continuous laboratory monitoring, clinical observation and, if needed, specific treatment, especially in severe cases of infection and in persons with additional liver pathologies. The pandemic can be an opportunity to provide equal access to care for all and increase the resilience of the transgender population.

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“…Notably, ICP is a disorder of the liver usually observed in mid‐ and late‐pregnancy that leads to perinatal asphyxia and, in some severe cases, newborn death (Gabzdyl & Schlaeger, 2015; Ovadia & Williamson, 2016). ICP is currently thought to be associated with elevated levels of estrogens such as estradiol (Gabzdyl & Schlaeger, 2015; Zu et al , 2021). Normally, excess estradiol is transported by ABCC2 to the bile duct in its conjugated form of E 2 17βG (Morikawa et al , 2000).…”

Section: Introductionmentioning

confidence: 99%

Placing steroid hormones within the human ABCC3 transporter reveals a compatible amphiphilic substrate‐binding pocket

Wang

et al. 2023

The EMBO Journal

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The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple physiological processes and is involved in diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo-form and in complexed forms bound to either the conjugated sex hormones b-estradiol 17-(b-D-glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the hydrophilic patches in two transmembrane domains. Structural analysis combined with site-directed mutagenesis and ATPase activity assays revealed that ABCC3 possesses an amphiphilic substrate-binding pocket able to hold either conjugated hormone in an asymmetric pattern. These data build on consensus features of the substrate-binding pocket of MRPs and provide a structural platform for the rational design of inhibitors.

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The Pathological Mechanisms of Estrogen-Induced Cholestasis: Current Perspectives

Cited by 30 publications

References 95 publications

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications

Liver function in transgender persons: Challenges in the COVID-19 era

Placing steroid hormones within the human ABCC3 transporter reveals a compatible amphiphilic substrate‐binding pocket

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