ArticleBMC medicine2021
The effects of selected inhibitors on human fetal adrenal steroidogenesis differs under basal and ACTH-stimulated conditions.
Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 16 citations in OpenAlex.
- Blood steroid hormone profile and clinical outcomes following switching from metyrapone to osilodrostat in patients with Cushing disease.Endocrine journal · 2025Article
- Efavirenz-induced grade III gynecomastia in an HIV-positive male patient: a case report and literature review.Frontiers in medicine · 2025Article
- Abiraterone and Galeterone, Powerful Tools Against Prostate Cancer: Present and Perspective.Pharmaceutics · 2024Review
- Cushing's Disease: Long-Term Effectiveness and Safety of Osilodrostat in a Polish Group of Patients with Persistent Hypercortisolemia in the Experience of a Single Center.Biomedicines · 2023Article
- An integrated single-cell analysis of human adrenal cortex development.JCI insight · 2023Article
- Dexamethasone affects human fetal adrenal steroidogenesis and subsequent ACTH response in anFrontiers in endocrinology · 2023Article
- Cushing's syndrome: a combined treatment with etomidate and osilodrostat in severe life-threatening hypercortisolemia.Hormones (Athens, Greece) · 2022Review
- Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto-Placental Organ-on-Chip Platform.International journal of environmental research and public health · 2022Review
- Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells.Developmental cell · 2022Article
- Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report.BMC endocrine disorders · 2022Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDisordered fetal adrenal steroidogenesis can cause marked clinical effects including virilization of female fetuses. In postnatal life, adrenal disorders can be life-threatening due to the risk of adrenal crisis and must be carefully managed. However, testing explicit adrenal steroidogenic inhibitory effects of therapeutic drugs is challenging due to species-specific characteristics, and particularly the impact of adrenocorticotropic hormone (ACTH) stimulation on drugs targeting steroidogenesis has not previously been examined in human adrenal tissue. Therefore, this study aimed to examine the effects of selected steroidogenic inhibitors on human fetal adrenal (HFA) steroid hormone production under basal and ACTH-stimulated conditions.
methodsThis study used an established HFA ex vivo culture model to examine treatment effects in 78 adrenals from 50 human fetuses (gestational weeks 8-12). Inhibitors were selected to affect enzymes critical for different steps in classic adrenal steroidogenic pathways, including CYP17A1 (Abiraterone acetate), CYP11B1/2 (Osilodrostat), and a suggested CYP21A2 inhibitor (Efavirenz). Treatment effects were examined under basal and ACTH-stimulated conditions in tissue from the same fetus and determined by quantifying the secretion of adrenal steroids in the culture media using liquid chromatography-tandem mass spectrometry. Statistical analysis was performed on ln-transformed data using one-way ANOVA for repeated measures followed by Tukey's multiple comparisons test.
resultsTreatment with Abiraterone acetate and Osilodrostat resulted in potent inhibition of CYP17A1 and CYP11B1/2, respectively, while treatment with Efavirenz reduced testosterone secretion under basal conditions. ACTH-stimulation affected the inhibitory effects of all investigated drugs. Thus, treatment effects of Abiraterone acetate were more pronounced under stimulated conditions, while Efavirenz treatment caused a non-specific inhibition on steroidogenesis. ACTH-stimulation prevented the Osilodrostat-mediated CYP11B1 inhibition observed under basal conditions.
conclusionsOur results show that the effects of steroidogenic inhibitors differ under basal and ACTH-stimulated conditions in the HFA ex vivo culture model. This could suggest that in vivo effects of therapeutic drugs targeting steroidogenesis may vary in conditions where patients have suppressed or high ACTH levels, respectively. This study further demonstrates that ex vivo cultured HFAs can be used to evaluate steroidogenic inhibitors and thereby provide novel information about the local effects of existing and emerging drugs that targets steroidogenesis.
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