a1_Progesterone and estradiol are the foremost steroid hormones in human pregnancy. However, the origin of maternal progesterone has still not been satisfactorily explained, despite the generally accepted opinion that maternal LDL-cholesterol is a single substrate for placental synthesis of maternal progesterone. The question remains why the levels of progesterone are substantially higher in fetal as opposed to maternal blood. Hence, the role of the fetal zone of fetal adrenal (FZFA) in the synthesis of progesterone precursors was addressed. The FZFA may be directly regulated by placental CRH inducing an excessive production of sulfated 3β-hydroxy-5-ene steroids such as sulfates of dehydroepiandrosterone (DHEAS) and pregnenolone (PregS). Due to their excellent solubility in plasma these conjugates are easily transported in excessive amounts to the placenta for further conversion to the sex hormones. While the significance of C19 3β-hydroxy-5-ene steroid sulfates originating in FZFA for placental estrogen formation is mostly recognized, the question “Which maternal and/or fetal functions may be served by excessive production of PregS in the FZFA?“ - still remains open. Our hypothesis is that, besides the necessity to synthesize de novo all the maternal progesterone from cholesterol, it may be more convenient to utilize the fetal PregS. The activities of sulfatase and 3β-hydroxysteroid dehydrogenase (3β-HSD) are substantially higher than the activity of cytochrome P450scc, which is rate-limiting for the placental progesterone synthesis from LDL-cholesterol. However, as in the case of progesterone synthesis from maternal LDL-cholesterol, the relative independence of progesterone levels on FZFA activity may be a consequence of substrate saturation of enzymes converting PregS to progesterone., a2_Some of the literature along with our current data (showing no correlation between fetal and maternal progesterone but significant partial correlations between fetal and maternal 20α-dihydroprogesterone (Prog20α) and between Prog20α and progesterone within the maternal blood) indicate that the localization of individual types of 17β-hydroxysteroid dehydrogenase is responsible for a higher proportion of estrone and progesterone in the fetus, but also a higher proportion of estradiol and Prog20α in maternal blood. Type 2 17β-hydroxysteroid dehydrogenase (17HSD2), which oxidizes estradiol to estrone and Prog20α to progesterone, is highly expressed in placental endothelial cells lining the fetal compartment. Alternatively, syncytium, which is directly in contact with maternal blood, produces high amounts of estradiol and Prog20α due to the effects of type 1, 5 and 7 17β-hydroxysteroid dehydrogenases (17HSD1, 17HSD5, and 17HSD7, respectively). The proposed mechanisms may serve the following functions: 1) providing substances which may influence the placental production of progesterone and synthesis of neuroprotective steroids in the fetus; and 2) creating hormonal milieu enabling control of the onset of labor., M. Hill ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sust aining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3β-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5α/β-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus. and M. Hill ... [et al.].
The expression of sexually dimorphic phenotypes from a shared genome between males and females is a longstanding puzzle in evolutionary biology. Increasingly, research has made use of transcriptomic technology to examine the molecular basis of sexual dimorphism through gene expression studies, but even this level of detail misses the metabolic processes that ultimately link gene expression with the whole organism phenotype. We use metabolic profiling in Drosophila melanogaster to complete this missing step, with a view to examining variation in male and female metabolic profiles, or metabolomes, throughout development. We show that the metabolome varies considerably throughout larval, pupal and adult stages. We also find significant sexual dimorphism in the metabolome, although only in pupae and adults, and the extent of dimorphism increases throughout development. We compare this to transcriptomic data from the same population and find that the general pattern of increasing sex differences throughout development is mirrored in RNA expression. We discuss our results in terms of the usefulness of metabolic profiling in linking genotype and phenotype to more fully understand the basis of sexually dimorphic phenotypes., Fiona C. Ingleby, Edward H. Morrow., and Obsahuje bibliografii
Steroids are important marker s in pregnancy. Although estimating their levels separately in umbilical arterial (UA) and venous blood (UV) enable more precise insights into the functioning fetoplacental unit compared to using mixed umbilical blood (UM), selective aspiration of UA and UV is technically more demanding than collecting UM. We measured the levels of 67 unconjugated steroids and steroid polar conjugates in UA and UV using GC-MS in 80 women giving birth within weeks 28 to 42 of gestation. The samples were sorted into three groups: women entering labor within weeks 28- 32 (group A, n=19), weeks 33-37 (group B, n=19), and weeks 38-42 (group C, n=42) of gestation, respectively. The preterm labo rs were due to pathologies unrelated to steroid status. Most unconjugated steroids exhibited pronounced arteriovenous differences (AVD). The AVD were less distinct in more stable steroid conjugates. Most steroids positively correlate with gestational age, but unconjugated 5 β -reduced pregnanes show negative correlations, as do testosterone and androstenediol, substrates for the placental synthesis of estrogens. Tight correlations be tween steroids in UA and UV indicate that steroid measurements in UA, UV and UM can be accurately derived from each other, which is important for the diagnostics of steroid related diseases in newborns., A. Pašková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy