Nejvíce citovaný článek - PubMed ID 20580824
Steroid metabolome in fetal and maternal body fluids in human late pregnancy
The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/β-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.
- Klíčová slova
- 7α/β-hydroxy-androgens, DHEA, androstenediol, behavioral immune system, cortisol, disgust, estrogens, pregnancy, steroids, testosterone,
- MeSH
- dospělí MeSH
- lidé MeSH
- longitudinální studie MeSH
- mladý dospělý MeSH
- odpor * MeSH
- prospektivní studie MeSH
- první trimestr těhotenství MeSH
- steroidy krev MeSH
- těhotenství MeSH
- třetí trimestr těhotenství krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- steroidy MeSH
Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.
- Klíčová slova
- CNS disorder, endocrine disruption, gynecology, menopause, miscarriage, neurosteroid, pregnancy, preterm birth, progestagen, progesterone, progestin, progestogen,
- MeSH
- hormony MeSH
- lidé MeSH
- novorozenec MeSH
- progesteron * farmakologie fyziologie MeSH
- progestiny * farmakologie terapeutické užití MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- hormony MeSH
- progesteron * MeSH
- progestiny * MeSH
As gestational diabetes mellitus (GDM) is both a frequent and serious complication, steroid levels in pregnancy are extremely elevated and their role in pregnancy is crucial, this review focuses on the role of steroids and related substances in the GDM pathophysiology. Low SHBG levels are associated with insulin resistance and hyperinsulinemia, while also predicting a predisposition to GDM. Other relevant agents are placental hormones such as kisspeptin and CRH, playing also an important role beyond pregnancy, but which are synthesized here in smaller amounts in the hypothalamus. These hormones affect both the course of pregnancy as well as the synthesis of pregnancy steroids and may also be involved in the GDM pathophysiology. Steroids, whose biosynthesis is mainly provided by the fetal adrenal glands, placenta, maternal adrenal glands, and both maternal and fetal livers, are also synthesized in limited amounts directly in the pancreas and may influence the development of GDM. These substances involve the sulfated ?5 steroids primarily acting via modulating different ion channels and influencing the development of GDM in different directions, mostly diabetogenic progesterone and predominantly anti-diabetic estradiol acting both in genomic and non-genomic way, androgens associated with IR and hyperinsulinemia, neuroactive steroids affecting the pituitary functioning, and cortisol whose production is stimulated by CRH but which suppresses its pro-inflammatory effects. Due to the complex actions of steroids, studies assessing their predominant effect and studies assessing their predictive values for estimating predisposition to GDM are needed.
- MeSH
- estradiol MeSH
- gestační diabetes * MeSH
- lidé MeSH
- placenta MeSH
- progesteron MeSH
- steroidy MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- estradiol MeSH
- progesteron MeSH
- steroidy MeSH
Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.
- Klíčová slova
- gas chromatography-tandem mass spectrometry, gestational age, gestational diabetes mellitus, immunoprotective steroids, maternal blood, mixed cord blood, neuroactive steroids, steroidome,
- MeSH
- 20-hydroxysteroid dehydrogenasy metabolismus MeSH
- chromatografie plynová MeSH
- cytochrom P-450 CYP3A metabolismus MeSH
- druhý trimestr těhotenství metabolismus MeSH
- gestační diabetes metabolismus MeSH
- lidé MeSH
- metabolomika metody MeSH
- oxidoreduktasy metabolismus MeSH
- steroid-17-alfa-hydroxylasa metabolismus MeSH
- steroidy analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 20-hydroxysteroid dehydrogenasy MeSH
- 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase MeSH Prohlížeč
- 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Prohlížeč
- CYP17A1 protein, human MeSH Prohlížeč
- CYP3A7 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP3A MeSH
- oxidoreduktasy MeSH
- steroid-17-alfa-hydroxylasa MeSH
- steroidy MeSH
Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.
- MeSH
- 17-alfa-hydroxypregnenolon krev chemie MeSH
- 17-alfa-hydroxyprogesteron krev chemie MeSH
- alanintransaminasa krev MeSH
- aspartátaminotransferasy krev MeSH
- dospělí MeSH
- gestační stáří MeSH
- hydrokortison krev chemie MeSH
- intrahepatální cholestáza diagnóza metabolismus patologie MeSH
- jaterní testy MeSH
- komplikace těhotenství diagnóza metabolismus patologie MeSH
- lidé MeSH
- nuclei raphe dorsalis MeSH
- plocha pod křivkou MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- radioimunoanalýza MeSH
- ROC křivka MeSH
- steroidy krev chemie metabolismus MeSH
- těhotenství MeSH
- žlučové kyseliny a soli analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 17-alfa-hydroxypregnenolon MeSH
- 17-alfa-hydroxyprogesteron MeSH
- alanintransaminasa MeSH
- aspartátaminotransferasy MeSH
- hydrokortison MeSH
- steroidy MeSH
- žlučové kyseliny a soli MeSH