WITHDRAWN: Physiological roles of steroid sulfatase. A minireview.
This paper has been withdrawn by publisher at the authors request.
Journal Article↗
Biomedical subjects
R Hampl
Publications and source records attributed to R Hampl.
Steroids and thermogenesis.
Apart from thyroid hormones, as the main hormonal regulators of obligatory thermogenesis, and catecholamines, as major hormonal regulators of facultative thermogenesis, production of heat in homeotherms can also be influenced by steroids. Generally, hormones can influence heat production by regulating the activity of various enzymes of oxidative metabolism, by modulating membrane protein carriers and other membrane or nuclear protein factors. Proton carriers in the inner mitochondrial membrane, known as uncoupling proteins, play the key role in heat dissipation to the detriment of the formation of energy-rich phosphates. In this minireview we have focused on the effects of steroids and thyroid hormones on heat production in brown adipose tissues and in skeletal muscles, with particular respect to their effect on uncoupling protein expression. Apart from hormonal steroids, dehydroepiandrosterone, an important precursor in the metabolic pathway leading to hormonal steroids which possess many, mostly beneficial effects on human health, modulates metabolic pathways which may lead to increased heat production. Recent studies demonstrate that 7-oxo-dehydroepiandrosterone, one of its 7-oxygenated metabolites, is even more effective than dehydroepiandrosterone. Recent findings of various actions of these steroids support the view that they may also participate in modulating thermogenic effects.
Adrenal Cortex Hormones↗
How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influence thyroid function.
Dehydroepiandrosterone may influence thyroid function. Its metabolite, 7-oxo-dehydroepiandrosterone, a precursor of immunomodulatory 7-hydroxylated metabolites and thermogenic agent, belongs to candidates of steroid replacement therapy. The question was addressed whether its application does influence laboratory parameters of thyroid function. 7-Oxo-dehydroepiandrosterone in the form of emulgel, 25 mg/day, was applied transdermally to 21 healthy men for 8 consecutive days. Morning blood was collected before the treatment (Day 0, Stage 1), during treatment (Day 5, Stage 2), on the first day after the last administration (Day 9, Stage 3), one week (Day 16, Stage 4), and 9 weeks (Day 72, Stage 5) after treatment termination. The levels of thyrotropin, free thyroxine and triiodothyronine, dehydroepiandrosterone, its sulfate and its 7-hydroxyepimers were measured. The changes were evaluated by analysis of variance and correlation analysis. During treatment a significant rise of 7beta-hydroxy-dehydroepiandrosterone was observed, which persisted 1 week after treatment termination. No changes were observed in dehydroepiandrosterone and its sulfate. Though a slight but significant rise of TSH and of both thyroid hormones occurred during treatment, its levels soon returned to the basal values. It was concluded that treatment of 7-oxo-dehydroepiandrosterone affects the thyroid parameters only temporarily and that it provides a considerable persistent amount of 7beta-hydroxy-dehydroepiandrosterone.
Administration, Cutaneous↗
Decrease in serum dehydroepiandrosterone level after fenofibrate treatment in males with hyperlipidemia.
The influence of steroid hormones on plasma lipids and lipoproteins was confirmed by many studies. On the other hand, the effect of plasma lipids on metabolism of steroid hormones has so far not been examined. The objective of this research project was to determine (1) the levels of cortisol, testosterone, estradiol, dehydroepiandrosterone (DHEA), its sulfate (DHEAS), 7-hydroxylated DHEA, and SHBG in men suffering from mixed hyperlipidemia (HPL) (n=23, age 46.1+/-7.9 years) in comparison with healthy male volunteers (n=17, age 45.1+/-15.6 years); (2) whether therapy with fenofibrate influences the levels of the above mentioned steroids and SHBG; (3) what are the correlations between lipids and steroids in healthy males and HPL patients before and after therapy. Compared to controls, untreated patients had significantly higher estradiol and free testosterone index (IFT) levels (p<0.0003 and p<0.02, respectively) and significantly lower SHBG (p<0.02). Due to fenofibrate therapy, a significant decrease of TC, TG, and DHEA levels occurred (mean decrease: 14 %, 52 % and 21 %, respectively). Triglycerides correlated negatively with testosterone and SHBG in healthy subjects. HDL-C correlated positively and consequently, atherogenic index correlated negatively with 7-hydroxylated epimers of DHEA in treated patients. This is the first study dealing with the influence of fenofibrate administration on the steroid levels. Taking together, the most important is the finding of decrease DHEA levels after fenofibrate therapy. It could be explained, at least in part, by the effect of the fenofibrateon on the biosynthesis of DHEA and its regulation.
Adult↗
Pregnanolone isomers, pregnenolone and their polar conjugates around parturition.
The levels of four pregnanolone isomers and their polar conjugates and pregnenolone sulfate were measured in the plasma of 13 and 7 women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma using a simple quadrupole GC/MS system with electron impact ionization (pregnenolone isomers), RIA following HPLC separation (pregnenolone) and specific RIA (pregnanolone sulfate). The concentration of epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one) in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3beta-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal, while the differences in 3alpha-hydroxy-isomers were insignificant. The differences in conjugates were insignificant with the exception of allopregnanolone, the levels of which were lower in umbilical plasma. In all the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. In addition, time profiles of the steroids were measured around parturition and in the postpartum period in the maternal serum. Similarly, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. Changes in concentrations of free steroids exhibited a similar pattern, with a fall primarily within the first hour after delivery. The decrease in conjugated steroids was shifted to the interval within the first hour and first day after delivery, and the changes were more pronounced. The time profiles of the conjugated/free steroid ratio exhibited a significant decrease within the first hour and the first day after delivery in all of the isomers investigated. A decrease was also observed in the ratio of 3alpha/3beta-isomers and 5alpha/5beta-isomers around parturition. The possible physiological consequences of the findings are indicated.
Female↗
[Metformin has a positive effect on disorders of carbohydrate metabolism in long-term care with low doses of prednisone].
BACKGROUND: The influence of long-term, low doses of prednison administration (< 0.3 mg/kg/day) on glucoregulation and glucose tolerance was studied in 20 female patients (15-20 yrs), including verification of possibility to correct the impairment of glucose tolerance (IGT) by metformin (M). METHODS AND RESULTS: During prednison treatment, we found typical signs of insulin resistance manifestation: HOMAIR 3.55 (5.13), blood insulin/glucose ratio 3.8 (5.84), QUICKI 0.61 (0.124). These were associated with higher Langerhans (L.) islets hormone secretion detected under basal conditions as well as after bolus of 5 g arginine chloride. However, detailed analysis of hormone secretion ratios revealed distinct signs of L. islets function impairment and subcompensation. Specifically, low ratio C peptide/proinsulin and C peptide/glucagon were characteristicaly observed. Six months of M. administration (1000 mg/day) had a beneficial effect on glucose metabolisms deviations as indicated by the following: insulin resistance decreased (HOMAIR 1.96 (1.60), insulin/glucose ratio 2.34 (1.52), QUICKI increased at 0.699 (0.238)). At the same time we found a decrease in the basal levels of insulin, proinsulin, glucagon, C peptide and amyline, and AUC proinsulin and glucagon as well. HOMAsecretion decreased from an initial value of 389 (376) to 207 (119). CONCLUSIONS: Judging by the new hormonal secretion ratios, the L. islets' function following M. treatment substantially improved. From the clinical point of view, it is important to note that M. was tolerated very well. No patient interrupted the follow up because of M. intolerance. IGT in the whole group normalised, in spite of the fact that no accent was put on the regime, diet including. The 90% of lactate values did not exceed 1.7 mmol/l. Based on the results, we may conclude that M. has a beneficial effect on long-term, low doses of glucocorticoid-related (induced) glucose metabolism impairment, and therefore, M. administration could be recommended, particularly in the situations with higher levels of glycosylated hemoglobin.
Adolescent↗
[Role of the steroids, SHBG, IGF-1, IGF BP-3 and growth hormone in glucose metabolism disorders during long-term treatment with low doses of glucocorticoids].
BACKGROUND: The relationships between selected steroids, SHBG, growth hormone, IGF-1, IGF BP-3 and indicators of glucose metabolism were studied in the group of 20 female patients (15-20 yrs) on long-term treatment with low prednisone doses (< 0.3 mg/kg/day) (baseline phase) and after adding 1000 mg of metformin per day for following 6 months to improve impaired glucose metabolism (control phase). METHODS AND RESULTS: Lower basal DHEAS and DHEA (DHEA/S) levels were found as compared with reference values. Only DHEAS level returned into the reference range after the treatment with metformin. Decrease of DHEA/S depended on the doses (DHEAS -0.7621, DHEA -0.7685). Positive correlations between DHEA/S and of the results insulin tolerance were found as at the baseline (+0.4452, resp. +0.4455) as well as in the control period after the metformin administration (+0.7549, resp. +0.6073). Testosterone (T) and dihydrotestosterone(DHT) values were within the reference range during the whole study. Due to very low SHBG levels higher free androgen index (FAI) was recorded in more than half of the patients. Significant relationships were revealed between former gonadal androgens and indicators of glucose metabolism deterioration at the control phase: T correlated: with fasting insulin (+0.6005), with HOMAIR (+0.5380), with insulin/glucose (+0.5261), with fasting glucose (+0.9268), with AUC glucose (+0.6792), FAI: with fasting insulin (+0.5560), with HOMAIR (+0.5269), with fasting glucose (+0.9025), with AUC glucose (+0.7143), DHT: with fasting C peptide (+0.7921), with AUC C peptide (+0.7143). SHBG correlated: with fasting glucose (-0.6519), and with AUC glucose (-0.5868). The tendency of GH to lower, and IGF-1, IGF BP-3 to higher values at the baseline changed at the control phase: fasting and AUC value of GH increased (signif.), while were IGF-1 (nonsignif.) and IGF BP-3 (signif.) levels decreased. Surprisingly, no correlation was observed between GH and parameters of glucose metabolism. Contrary to GH, baseline IGFBP-3 values correlated: with HOMAIR (+0.5002), with insulin/glucose (+0.4860). The same relationships were found between AUC IGF BP-3 (+0.5676, +0.5559), IGF-1 (HOMAIR only +0.5412), IGF-1/IGF BP-3 (+0.5059, +0.5716) and parameters of insulin sensitivity (HOMAIR, insulin/glucose) in the control period. For the first time negative correlations between IGF-1, IGF-1 AUC, IGF BP-3, IGF-1/IGF BP-3 and somatostatin blood levels were discovered at the control phase. CONCLUSIONS: The study brought a number of new information about the importance of the "non-classical" glucoregulatory hormones in impairment of glucose metabolism, during long-term administration of low prednisone doses. The results suggest, that without normalisation of low DHEA/S, SHBG and high FAI levels it would not be possible to correct glucose metabolism properly in patients with long-term glucocorticoid therapy.
Adolescent↗
Time-resolved fluoroimmunoassay of plasma and urine O-desmethylangolensin.
We present a method for the determination of the phytoestrogen metabolite O-desmethylangolensin (O-DMA) in plasma (serum) and in urine. O-DMA is a metabolite of daidzein, which occurs in soybeans. It has been suggested that isoflavones may afford protection against breast and prostate cancer and therefore, also the metabolites are of interest. The method is based on time-resolved fluoroimmunoassay (TR-FIA) using a europium chelate as a label. After the synthesis of 4"-O-carboxymethyl-O-DMA, this compound is coupled to bovine serum albumin, and then used as antigen in immunization of rabbits. The tracers with the europium chelate are synthesized using the same 4"-O-derivative of the alpha-methyldeoxybenzoin. After enzymatic hydrolysis and ether extraction the immunoassay is carried out by time resolved fluoroimmunoassay (TR-FIA). Cross-reactivity was tested with angolensin, dihydrogenistein, dihydrodaidzein, equol, 6'-OH-angolensin, trans-4-OH-equol, 6'-OH-O-DMA, cis-4-OH-equol and 5-OH-equol. The antiserum cross-reacted only with angolensin. This cross-reactivity seems not to influence the results, which were highly specific. Plasma samples are hydrolyzed and extracted. Urine samples are analyzed directly after hydrolysis without extraction. The correlation coefficient between the plasma TR-FIA results and the GC-MS results was high; r value was 0.985. The correlation coefficient between the urine TR-FIA results and the GC-MS results was high over the entire range of concentrations (0-1500 nmol/l); r value was 0.976, but lower in the low concentration range (0-100 nmol/l), i.e. value was 0.631. The intra-assay coefficients of variation (CVs) for plasma O-DMA concentrations and for urine O-DMA concentrations at three different concentrations varied 2.8-7.7 and 3.0-6.0%, respectively and the inter-assay CVs varied 3.8-8.9 and 4.4-6.6%, respectively. The working range of the plasma and urine O-DMA assays was 0.5-512 nmol/l.
Animals↗
Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal and umbilical blood: 3.3beta-hydroxy-5-ene steroids.
Five 3beta-hydroxy-5-ene steroids involved in the metabolic route from pregnenolone sulfate to dehydroepiandrosterone and its sulfate, of which three are known allosteric modulators of neurotransmitter receptors, were monitored in the serum of 20 women around parturition. In addition, their levels in maternal and umbilical serum were compared at delivery. On the basis of these data, a scheme of steroid biosynthesis in maternal organism during the critical stages around parturition is proposed. In maternal serum, all the steroids except dehydroepiandrosterone sulfate decreased during labor and even first day after delivery, although their changes were less distinct the more distant from pregnenolone sulfate (PregS) in the metabolic pathway. Calculation of product/immediate precursor ratios in maternal serum over all stages around parturition enabled identification of the respective changes in the activities of the relevant enzymes. The ratio of 17-hydroxypregnenolone/pregnenolone did not change significantly, while that of dehydroepiandrosterone/17-hydroxypregnenolone grew, indicating increased C17,20 side chain cleavage on the account of C17-hydroxylation both catalyzed by C17-hydroxylase-C17,20-lyase. As was shown by factor analysis, the changes in the maternal steroids were associated with a single common factor, which strongly correlated with all the steroids except dehydroepiandrosterone sulfate. The lack of change in the pregnenolone sulfate/pregnenolone ratio and a marked increase of the ratio dehydroepiandrosterone sulfate to unconjugated dehydroepiandrosterone indicate a different means of formation of both steroid sulfates. On the basis of these data, a scheme of steroid biosynthesis in maternal organism during the critical stages around parturition is proposed.
Female↗
7-Hydroxydehydroepiandrosterone epimers in human serum and saliva. Comparison of gas chromatography-mass spectrometry and radioimmunoassay.
Recent reports demonstrated that 7-hydroxylated metabolites of dehydroepiandrosterone (DHEA) possess immunomodulatory and antiglucocorticoid properties. Increased 7alpha-OH-DHEA levels were found in patients with Alzheimer's disease. Hence, measurement of steroids in patients with autoimmune diseases or disturbances in the central nervous system could be of interest. A new sensitive GC-MS method for the determination of 7-hydroxydehydroepiandrosterone epimers was developed and compared with previously developed radioimmunoassays. Besides serum, these steroids were, for the first time, measured in saliva where their concentrations were about five times lower. 7alpha- and 7beta-epimer levels correlated well in both body fluids and they were larger in male.
Adolescent↗
Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers.
Time profiles of the pregnanolone isomers epipregnanolone (3 beta-hydroxy-5 beta-pregnan-20-one), allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one), and isopregnanolone (3 beta-hydroxy-5 alpha-pregnan-20-one) were measured around parturition and in the postpartum period in the serum of 13 and three women with subarachnoidal and epidural analgesia, respectively. In addition, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. GC/MS analysis was used for the measurement of steroid levels. Changes in concentrations of free steroids exhibited a similar pattern, with a fall primarily within the first hour after delivery. The decrease in conjugated steroids was shifted to the interval within the first hour and first day after delivery, and the changes were more pronounced. The time profile of the conjugated/free steroid ratio exhibited a significant decrease within the first hour and the first day after delivery in all of the isomers investigated. A decrease was also observed in the ratio of 3 alpha/3 beta-isomers and 5 alpha/5 beta-isomers around parturition. The possible physiological consequences of the findings are indicated.
Adult↗
7-Hydroxydehydroepiandrosterone epimers in the life span.
Evidence has been accumulated that 7-hydroxyepimers of dehydroepiandrosterone (7-OH-DHEA), may act as locally active immunomodulatory and immunoprotective agents, counteracting exaggerated actions of glucocorticoids. Since Skinner et al. (1977) developed the first unspecific RIA, it has been known that 7alpha-OH-DHEA is present in near nanomolar concentration in human blood. No data have been available, however, on its changes during the human life. Using recently developed specific radioimmunoassays for determination of both 7-OH-DHEA epimers, 7alpha- and 7beta-OH-DHEA were measured in sera from 252 males and 172 females, representing age groups from 10 to 91 years (males) and from 10 to 72 years (females). The dependence of 7-OH-DHEA levels on age was evaluated by using polynomial fitting of the 4th or 5th degree. In contrast to men, where a distinct decline with age occurred, two local maxima have been recorded round the age 22 and 53, respectively, in females. The curves of age dependence of 7-OH-DHEA levels in both sexes resembled those of previously determined unconjugated DHEA, but in the latter case the second maximum in women was found about 10 years earlier than 7-OH-DHEA, in a premenopausal period. The levels of both 7-OH-DHEA epimers correlated excellently with each other.
Adolescent↗
Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men.
The aim of this study was to investigate the effect of 7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of steroid sexual hormones, gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone, estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B and lipoprotein(a) were measured before the beginning and shortly after the end of the steroid application. After the treatment, we noted the following significant changes: a decline of testosterone and estradiol levels, increase of LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total cholesterol levels was of the borderline significance. A slight but significant increase was found in apolipoprotein B and lipoprotein(a). The most expressive was the fall of the atherogenic index. We suggest that the gel containing 7-oxo-DHEA might be a suitable drug for improving the composition of the steroid and lipid parameters in elderly men.
Administration, Cutaneous↗
Sex hormone-binding globulin as a marker of the effect of hormonal treatment in Turner's syndrome.
OBJECTIVE: In girls with Turner's syndrome a positive effect of growth hormone (GH) therapy on statutal growth has been well documented, in spite of the fact that the levels of GH and IGF-I in these patients are usually within the normal range. It is known that plasma levels of sex hormone-binding globulin (SHBG) are negatively associated with growth hormone (GH) and with [GF-I. Limited data on SHBG levels in these patients and only scarce reports on other than gonadal steroids in these patients are available so far. The major aim of this study was to find out whether SHBG does respond to GH treatment. METHODS: Plasma levels of SHBG, estradiol, progesterone, testosterone and the adrenal steroids and their precursors, namely cortisol, 17alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone and its sulfate were determined in 65 patients aged 2-23 years with Turner's syndrome. The patients were divided into 4 groups according to their actual treatment (untreated, sex steroids only, GH only, GH and sex steroids) and the differences between the groups were evaluated. With respect to dependence of SHBG and of steroids studied on age (with exception of cortisol), their values were expressed as per cents of medians of the physiological values. RESULTS: As expected, low levels of sex steroids were found. As to the adrenal steroids, in general, their average levels were lower than in healthy subjects but still within the physiological limits. With one exception (androstenedione), no significant differences were found between the groups. The levels of cortisol were undistinguishable from healthy subjects. Absolute as well as relative SHBG levels in untreated group and in the group treated with estrogens were normal or even lower than those reported for normal subjects of the same chronological age. Significantly reduced absolute as well as relative SHBG levels in comparison to all other groups were found in GH treated children. CONCLUSION: The results indicate that SHBG may serve as a sensitive biochemical marker of the response to the GH administration.
17-alpha-Hydroxyprogesterone↗
Genetic variant of luteinizing hormone: impact on gonadal steroid sex hormones in women.
A common variant of the LHbeta subunit has a varying prevalence in various ethnic groups. The consequences of the presence of mutated luteinizing hormone (LH) concern borderline alterations in pituitary/gonadal function that could be mediated by an altered action of variant LH on gonadal steroidogenesis. A comparison of plasma concentrations of gonadal steroid sex hormones was completed in women heterozygous for variant LH and in women with the wild type of LH in three different age ranges. The sample was a randomly selected group of 177 normal women 16 to 72 years old. Variant LH was determined by immunofluorimetric methods using two combinations of monoclonal antibodies. The ratios of LH measured by the two assays indicated whether the subject was wild type homozygote, heterozygote or homozygote for the variant LHbeta allele. The carriers of the variant LH allele in the group of postmenopausal women showed higher serum testosterone levels than those with the wild type LH. This is in agreement with the clinical observations made previously showing a slightly higher androgenic action in the population with variant LH. No differences were detected in serum LH, FSH, epitestosterone and sex hormone binding globulin (SHBG).
Adolescent↗
Immunomodulatory 7-hydroxylated metabolites of dehydroepiandrosterone are present in human semen.
Seminal fluid represents a milieu enabling spermatozoa to break the ovum membrane and suppress its immune response and, at the same time, to protect male germ cells against infection. Among constituents of the seminal fluid, various steroids, including dehydroepiandrosterone (DHEA) and its sulphate, were detected. With respect to immunomodulatory and antioxidative properties of the latter steroid and its 7-hydroxylated metabolites, believed to be at least in some instances the locally active species, their presence in seminal fluid is of particular interest. Here for the first time unconjugated 3beta,7alpha-dihydroxy-5-androsten-17-one (7alpha-OH-DHEA) and its 7beta-hydroxyisomer have been detected and quantified in semen. Eight semen samples were extracted with diethyl ether and following evaporation and solvent partition both isomers were detected by gas chromatography-mass fragmentometry using the ions m/z 358 and 343 for quantification. Another portion was separated by HPLC and in the fractions corresponding to 7-OH-DHEA isomers the steroids were measured by recently developed specific radioimmunoassays (RIA). Mean concentrations of 7-OH-DHEA as measured by RIA amounted 5.75+/-1.29 and 5.39+/-0.75 nmol/l (mean+/-SEM) for 7alpha- and 7beta-OH-DHEA, respectively.
Adjuvants, Immunologic↗
Neuroactive steroids, their precursors, and polar conjugates during parturition and postpartum in maternal and umbilical blood: 1. Identification and simultaneous determination of pregnanolone isomers.
A rapid method for the identification and measurement of four pregnanolone isomers and their polar conjugates in human plasma was developed using a simple quadrupole GC/MS system with electron impact ionization. Steroid levels were measured in the plasma of 13 and three women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma. A good correlation (r=0.94, P<0.001, n=8) was found between the allopregnanolone in maternal plasma determined by GC/MS and that measured by RIA. Epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one) was identified and measured for the first time in human plasma; its concentration in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3beta-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal plasma, while the differences in 3alpha-hydroxy-isomers were insignificant. The differences in conjugates were insignificant except in the case of allopregnanolone, the levels of which were lower in umbilical plasma. In all of the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. The possible role of the sulfatation of pregnanolone isomers around parturition is discussed.
Adult↗
[Derivatives of dehydroepiandrosterone and their changes during a one-day starvation test].
BACKGROUND: Relationship between dehydroepiandrosterone (DHEA), its sulphate (DHEAS) and various components of metabolic syndrome X have been recently discussed in several papers. Originally only DHEA or DHEAS have been considered to be responsible for all of the effects. At present mainly DHEA hydroxyderivatives (particularly 7-hydroxyisometers) are assumed to be responsible for those effects. METHODS AND RESULTS: 68 obese subjects (28 males) aged 42.6 +/- 11.1 years, with average BMI 35.7 +/- 11.6 kg/m2 were examined. Relationship between 7-alpha and 7-beta-(OH)-DHEA and various components of metabolic syndrome X have been followed in a pilot epidemiological study. Fluctuations of the hydroxyderivates level during one-day starvation test were investigated in a group of 11 obese females and compared with that of the control group (12 lean subjects with BMI 23.1 +/- 2.4 kg/m2). From the view of the metabolic syndrome X, the negative correlation between the serum levels of 7-beta-(OH)-DHEA and insulinemia (r = -0.28; p = 0.23), glycemia (r = -0.48; p < 0.001), serum level of uric acid (r = -0.35; p = 0.02) and opposite the positive correlation between the serum level of HDL-cholesterol (r = 0.42; p < 0.01) should be pointed out. The negative correlation between 7-alpha-(OH)-DHEA and age and BMI was noticed (correlation for 7-beta-(OH)-DHEA was similar). No other statistically significant correlation was found among the other monitored parameters. In 11 obese females the dynamic changes of the above-mentioned DHEA hydroxyderivatives during one-day starvation test were monitored. Changes were compared with the control group (12 lean females). Significant increases in DHEAS, 7-beta-(OH)-DHEA, and sex hormone binding globulin (SHBG) levels were observed during this test. Significant differences in dynamic changes (before and after the test) between obese and lean group have been found only in DHEAS and SHBG. CONCLUSION: We suppose that 7-beta-(OH)-DHEA (more than 7-alpha-(OH)-DHEA) is specifically related to the metabolic syndrome X and that its claimed anti-glucocorticoid effect in the immune response can play some role in its metabolic effects.
Adult↗