Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf
Introduction<p>Increased CYP3A-mediated drug clearance during pregnancy can lead to subtherapeutic dosing of CYP3A substrates. Pregnancy-related hormones (PRHs) increase CYP3A4 expression and activity in cultured human hepatocytes. However, the factors in maternal circulation that regulate pre...
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| Beste egile batzuk: | , , , , , , , |
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2025
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Etiketa erantsi
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| _version_ | 1849927623149355008 |
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| author | Muluneh M. Fashe (13836118) |
| author2 | Jonghwa Lee (3918998) Joseph T. Grieco (22687382) John K. Fallon (1329057) Ian R. Mulrenin (16506765) Megan N. Gower (22687385) Klarissa D. Jackson (4744389) Kim A. Boggess (2882261) Craig R. Lee (10650905) |
| author2_role | author author author author author author author author |
| author_facet | Muluneh M. Fashe (13836118) Jonghwa Lee (3918998) Joseph T. Grieco (22687382) John K. Fallon (1329057) Ian R. Mulrenin (16506765) Megan N. Gower (22687385) Klarissa D. Jackson (4744389) Kim A. Boggess (2882261) Craig R. Lee (10650905) |
| author_role | author |
| dc.creator.none.fl_str_mv | Muluneh M. Fashe (13836118) Jonghwa Lee (3918998) Joseph T. Grieco (22687382) John K. Fallon (1329057) Ian R. Mulrenin (16506765) Megan N. Gower (22687385) Klarissa D. Jackson (4744389) Kim A. Boggess (2882261) Craig R. Lee (10650905) |
| dc.date.none.fl_str_mv | 2025-11-26T06:33:26Z |
| dc.identifier.none.fl_str_mv | 10.3389/fphar.2025.1702419.s001 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Data_Sheet_1_Estrogen_associations_with_human_pregnancy_related_increases_in_cytochrome_P450_3A_activity_pdf/30718637 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Pharmacology pregnancy CYP3A4 hepatic metabolism estrone estradiol 4β-hydroxycholesterol |
| dc.title.none.fl_str_mv | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Introduction<p>Increased CYP3A-mediated drug clearance during pregnancy can lead to subtherapeutic dosing of CYP3A substrates. Pregnancy-related hormones (PRHs) increase CYP3A4 expression and activity in cultured human hepatocytes. However, the factors in maternal circulation that regulate pregnancy-mediated changes in CYP3A activity remain unclear.</p>Methods<p>This study investigated the association between maternal plasma concentrations of key steroidal PRHs and biomarkers of CYP3A activity in human pregnancy, and the impact of individual PRHs on CYP3A4 expression in primary human hepatocytes. Concentrations of estrone (E1), estradiol (E2), progesterone (P4), and cortisol (CRT), and 4β-hydroxycholesterol (4β-OH-CHO) and the 4β-OH-CHO:CHO ratio (endogenous biomarkers of CYP3A activity), were quantified in human plasma across a spectrum of pregnancy states: healthy nonpregnant controls (n = 4), healthy pregnant volunteers (n = 6), and pregnant patients diagnosed with preeclampsia (n = 8).</p>Results<p>Plasma 4β-OH-CHO concentrations (median [25%–75%]) were higher in healthy pregnant (141 [115, 165] ng/mL) and preeclampsia patients (129 [90.5, 191] ng/mL) compared to nonpregnant controls (69.8 [45.8, 82.5] ng/mL). In healthy pregnant and preeclampsia patients, plasma E1 (r = 0.687, p = 0.007) and E2 (r = 0.551, p = 0.041) concentrations positively correlated with plasma 4β-OH-CHO concentrations. Conversely, no association between P4 (r = 0.068, p = 0.817) or CRT (r = -0.115, p = 0.696) concentrations and 4β-OH-CHO were observed. Cultured human female primary hepatocytes were exogenously exposed in vitro to PRHs and absolute CYP protein concentrations were quantified. Consistent with the human plasma sample associations, E1 and E2 induced CYP3A4 mRNA and total CYP3A protein concentrations in a concentration-dependent manner.</p>Discussion<p>Altogether, these data suggest that increased concentrations of E1 and E2 contribute, at least in part, to increased hepatic CYP3A expression and activity during pregnancy in humans.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_7ea3e57807c693f1b7c31e8590cc4bc8 |
| identifier_str_mv | 10.3389/fphar.2025.1702419.s001 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30718637 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdfMuluneh M. Fashe (13836118)Jonghwa Lee (3918998)Joseph T. Grieco (22687382)John K. Fallon (1329057)Ian R. Mulrenin (16506765)Megan N. Gower (22687385)Klarissa D. Jackson (4744389)Kim A. Boggess (2882261)Craig R. Lee (10650905)PharmacologypregnancyCYP3A4hepatic metabolismestroneestradiol4β-hydroxycholesterolIntroduction<p>Increased CYP3A-mediated drug clearance during pregnancy can lead to subtherapeutic dosing of CYP3A substrates. Pregnancy-related hormones (PRHs) increase CYP3A4 expression and activity in cultured human hepatocytes. However, the factors in maternal circulation that regulate pregnancy-mediated changes in CYP3A activity remain unclear.</p>Methods<p>This study investigated the association between maternal plasma concentrations of key steroidal PRHs and biomarkers of CYP3A activity in human pregnancy, and the impact of individual PRHs on CYP3A4 expression in primary human hepatocytes. Concentrations of estrone (E1), estradiol (E2), progesterone (P4), and cortisol (CRT), and 4β-hydroxycholesterol (4β-OH-CHO) and the 4β-OH-CHO:CHO ratio (endogenous biomarkers of CYP3A activity), were quantified in human plasma across a spectrum of pregnancy states: healthy nonpregnant controls (n = 4), healthy pregnant volunteers (n = 6), and pregnant patients diagnosed with preeclampsia (n = 8).</p>Results<p>Plasma 4β-OH-CHO concentrations (median [25%–75%]) were higher in healthy pregnant (141 [115, 165] ng/mL) and preeclampsia patients (129 [90.5, 191] ng/mL) compared to nonpregnant controls (69.8 [45.8, 82.5] ng/mL). In healthy pregnant and preeclampsia patients, plasma E1 (r = 0.687, p = 0.007) and E2 (r = 0.551, p = 0.041) concentrations positively correlated with plasma 4β-OH-CHO concentrations. Conversely, no association between P4 (r = 0.068, p = 0.817) or CRT (r = -0.115, p = 0.696) concentrations and 4β-OH-CHO were observed. Cultured human female primary hepatocytes were exogenously exposed in vitro to PRHs and absolute CYP protein concentrations were quantified. Consistent with the human plasma sample associations, E1 and E2 induced CYP3A4 mRNA and total CYP3A protein concentrations in a concentration-dependent manner.</p>Discussion<p>Altogether, these data suggest that increased concentrations of E1 and E2 contribute, at least in part, to increased hepatic CYP3A expression and activity during pregnancy in humans.</p>2025-11-26T06:33:26ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.3389/fphar.2025.1702419.s001https://figshare.com/articles/dataset/Data_Sheet_1_Estrogen_associations_with_human_pregnancy_related_increases_in_cytochrome_P450_3A_activity_pdf/30718637CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307186372025-11-26T06:33:26Z |
| spellingShingle | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf Muluneh M. Fashe (13836118) Pharmacology pregnancy CYP3A4 hepatic metabolism estrone estradiol 4β-hydroxycholesterol |
| status_str | publishedVersion |
| title | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| title_full | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| title_fullStr | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| title_full_unstemmed | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| title_short | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| title_sort | Data Sheet 1_Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.pdf |
| topic | Pharmacology pregnancy CYP3A4 hepatic metabolism estrone estradiol 4β-hydroxycholesterol |