Effects of testosterone on the metabolism of folate coenzymes in the rat.
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ABSTRACT:
SUBMITTER: Rovinetti C
PROVIDER: S-EPMC1178379 | biostudies-other | 1972 Jan
REPOSITORIES: biostudies-other
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Project description:1. The effects of thyroidectomy and of ;acute' and ;chronic' administration of thyroxine on the synthesis of folate coenzymes were studied by determining the liver contents of folate active derivatives and the enzymic activities involved in their biosynthesis. The effect of thyroxine on the same enzymes in vitro was also studied. 2. In thyroidectomized rats the liver contents of folate coenzymes did not change except for a slight decrease in the contents of 5-formyltetrahydrofolate and tetrahydrofolate compared with those in control rats. 3. In the same animals serine hydroxymethyltransferase and formyltetrahydrofolate synthetase activities decreased markedly. 4. The ;chronic' administration of thyroxine to thyroidectomized rats caused more evident variations in the liver contents of folate coenzymes and in particular a decrease in the contents of 5-formyltetrahydrofolate, tetrahydrofolate, 5(or 10)-formyl derivatives of tetrahydropteroylpolyglutamate and of 5(or 10)-formyl derivatives of pteroylpolyglutamate. 5. The enzymic activities did not show significant variations. 6. The ;acute' administration of thyroxine caused changes in the liver contents of some folate derivatives such as 10-formyldihydrofolate, 10-formylfolate, tetrahydrofolate and the 10-formyl derivative of dihydropteroylpolyglutamate. In these animals also the enzymic activities were unchanged. 7. No effect of thyroxine on enzymic activities in vitro was observed.
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Project description:Folate metabolism in mammalian cells is essential for multiple vital processes, including purine and pyrimidine synthesis, histidine catabolism, methionine recycling, and utilization of formic acid. It remains unknown, however, whether these processes affect each other via folate metabolism or can function independently based on cellular needs. We addressed this question using a quantitative mathematical model of folate metabolism in rat liver cytoplasm. Variation in the rates of metabolic processes associated with folate metabolism (i.e., purine and pyrimidine synthesis, histidine catabolism, and influxes of formate and methionine) in the model revealed that folate metabolism is organized in a striking manner that enables activation or inhibition of each individual process independently of the metabolic fluxes in others. In mechanistic terms, this independence is based on the high activities of a group of enzymes involved in folate metabolism, which efficiently maintain close-to-equilibrium ratios between substrates and products of enzymatic reactions.
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Project description:The use of crude kerosene as a dietary supplement in boarding schools has been a common practice in east Africa and other countries for many years, with the belief of it reducing the sex drive (libido) at the pubertal stage. There is however no scientific basis for this belief. The present study aimed at using a rat animal model to investigate the effects of crude kerosene on serum testosterone levels, aggression and its possible toxic effects. Fifteen male albino rats of approximately similar age and average weights were put into three groups of five animals each; the control group (placebo), low kerosene dose (10 ?l/day) group and high kerosene dose (300 ?l/day) group. ELISA was used to determine the serum testosterone levels. During treatment, changes in aggression were observed and noted. Liver toxicity was determined using enzyme assays, total protein and albumin while renal toxicity was monitored using serum creatinine levels. A full hemogram was conducted to determine hematological effects. Various tissue biopsies were obtained and examined using histopathological techniques for evidence of toxicity. Contrary to the common belief, our findings showed an overall increase of serum testosterone levels of up to 66% in the low dose and 75% in the high dose groups, with an increasing trend by the end of the study. The high dose group showed significantly increased levels of white blood cells (WBC) (p = 0.036), red blood cells (RBC) (p = 0.025), hematocrit (HCT) (p = 0.03), red cell distribution width (p = 0.028) and platelets (p = 0.017). The histological results of the stomach indicated chronic gastritis.
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Project description:The importance of maternal folate consumption for normal development is well established, yet the molecular mechanism linking folate metabolism to development remains poorly understood. The enzyme methionine synthase reductase (Mtrr) is necessary for utilization of methyl groups from the folate cycle. We found that a hypomorphic mutation of the mouse Mtrr gene results in intrauterine growth restriction, developmental delay, and congenital malformations, including neural tube, heart, and placental defects. Importantly, these defects were dependent upon the Mtrr genotypes of the maternal grandparents. Furthermore, we observed widespread epigenetic instability associated with altered gene expression in the placentas of wild-type grandprogeny of Mtrr-deficient maternal grandparents. Embryo transfer experiments revealed that Mtrr deficiency in mice lead to two distinct, separable phenotypes: adverse effects on their wild-type daughters' uterine environment, leading to growth defects in wild-type grandprogeny, and the appearance of congenital malformations independent of maternal environment that persist for five generations, likely through transgenerational epigenetic inheritance.
| S-EPMC3844871 | biostudies-literature
Project description:A dramatic difference exists in the timing of development of cardiovascular disease in men vs. women. The primary candidates underlying the cause of this gender difference are the sex steroids, estrogen and testosterone. The vasculature is considered to be a site of action of these steroids. In spite of these concepts there is little data on the direct effects of estrogen and testosterone on gene expression in the vasculature. In this study, ovariectomized Sprague Dawley rats were treated for 4 days with vehicle (sesame oil), estradiol benzoate (0.15 mg/kg/day), or testosterone (1 mg/kg/day). The mesenteric arteries were obtained, total RNA was extracted, and CodeLink Uniset Rat I DNA microarrays were used to identify differential gene expression. Seven genes were identified as differentially expressed from the DNA microarray data and confirmed by real time RT-PCR. The expression of D site albumin promoter binding protein and fatty acid synthase were increased in response to both estrogen and testosterone. 3 alpha-hydroxysteroid dehydrogenase, interleukin 4 receptor, JunB and c-Fos expression were increased by estrogen but not by testosterone. Aryl hydrocarbon nuclear translocator-like gene was reduced by testosterone. These data identify genes not previously known to be responsive to estrogen and testosterone in the vasculature.
| S-EPMC2080788 | biostudies-literature
Project description:Folate metabolism affects ovarian function, implantation, embryogenesis and the entire process of pregnancy. In addition to its well-established effect on the incidence of neural tube defects, associations have been found between reduced folic acid levels and increased homocysteine concentrations on the one hand, and recurrent spontaneous abortions and other complications of pregnancy on the other. In infertility patients undergoing IVF/ICSI treatment, a clear correlation was found between plasma folate concentrations and the incidence of dichorionic twin pregnancies. In patients supplemented with 0.4 mg/d folic acid undergoing ovarian hyperstimulation and oocyte pick-up, carriers of the MTHFR 677T mutation were found to have lower serum estradiol concentrations at ovulation and fewer oocytes could be retrieved from them. It appears that these negative effects can be compensated for in full by increasing the daily dose of folic acid to at least 0.8 mg. In carriers of the MTHFR 677TT genotype who receive appropriate supplementation, AMH concentrations were found to be significantly increased, which could indicate a compensatory mechanism. AMH concentrations in homozygous carriers of the MTHFR 677TT genotype could even be overestimated, as almost 20 % fewer oocytes are retrieved from these patients per AMH unit compared to MTHFR 677CC wild-type individuals.
| S-EPMC4175124 | biostudies-literature
Project description:1. Folate metabolism was studied during the early phases of liver regeneration after partial hepatectomy in rats accustomed to eating during the first 8h of a daily 12h dark period. 2. The content of 5-CH(3)-H(4)folate was drastically decreased during the first hours of regeneration. 3. The total HCO-H(4)folate coenzymes showed a constant decrease during the first 3 days of regeneration, and a continuous interconversion between 5-HCO-H(4)folate and 10-HCO-H(4)folate. 4. 10-HCO-H(4)folate synthetase, serine hydroxymethyl-transferase and 5,10-CH(2)-H(4)folate dehydrogenase activities were relatively low during the first hours after the operation, and increased only several hours later. 5. The increase in enzyme activities showed a stepwise pattern, apparently due to an interaction between the regeneration process and the controlled feeding schedules.
| S-EPMC1172464 | biostudies-other
Project description:1. Labelled testosterone, injected directly into the ventral prostate of castrated rats became associated, in part, with a cytoplasmic high-molecular-weight fraction, fraction ;A'. 2. The label present in fraction ;A' was found to be mainly associated with dihydrotestosterone. 3. Unlike fraction ;A' from testosterone-pelleted castrated rats, fraction ;A' obtained from untreated castrated rats, 48h or more after castration, was strongly inhibitory towards Escherichia coli RNA polymerase in vitro. 4. The inhibition of RNA polymerase by fraction ;A' from castrated rats was not changed by the addition of testosterone or dihydrotestosterone in vitro, but pre-heating it to 80 degrees C resulted in a loss of its inhibitory capacity. 5. Fraction ;A' from castrated rats contained ribonuclease activity. The elution profile of ribonuclease activity from Sephadex columns indicated that this activity was responsible for the inhibitory effect on the RNA polymerase assays. 6. It is concluded that, unlike the inhibitor present in the uterus of ovariectomized rats (Talwar, Segal, Evans & Davidson, 1964), no direct connexion exists between the steroid-binding capacity of prostatic fraction ;A' and its effect on E. coli RNA polymerase activity in vitro.
| S-EPMC1178943 | biostudies-other
Project description:Background and purposeTestosterone alleviates symptoms in patients with ischaemic heart disease. Androgen receptors are present in the heart, and testosterone upregulates gene expression of cardiac beta(1)-adrenoceptors. We hypothesize that testosterone may confer cardioprotection by interacting with adrenoceptors.Experimental approachIn isolated perfused hearts and ventricular myocytes from orchidectomized rats without or with testosterone (200 microg/100 g) replacement, we first determined the effect of ischaemia/reperfusion in the presence of noradrenaline (10(-7) M). Then we determined the contribution of interactions between testosterone and alpha(1)- or beta(1)-adrenoceptors in cardiac injury/protection (infarct size, release of lactate dehydrogenase, viability of myocytes, recovery of contractile function and incidence of arrhythmias) upon ischaemia/reperfusion by pharmacological manipulation using selective adrenoceptor agonists (alpha(1)-adrenoceptor agonist: phenylephrine 10(-6) M; non-selective beta-adrenoceptor agonist: isoprenaline 10(-7) M) and antagonists (alpha(1): prazosin or benoxathian 10(-6) M; beta(1): CGP 20712A 5 x 10(-7) M). We also determined the expression of alpha(1) and beta(1)-adrenoceptor in the hearts from rats with and without testosterone.Key resultsTestosterone reduced injury induced by ischaemia/reperfusion and noradrenaline. This was achieved by enhancing the beneficial effect of alpha(1)-adrenoceptor stimulation, which was greater than the deleterious effect of beta(1)-adrenoceptor stimulation (also enhanced by testosterone). The effects of testosterone were abolished or attenuated by blockade of androgen receptors. Testosterone also enhanced the expression of alpha(1A) and beta(1)-adrenoceptor.Conclusions and implicationsTestosterone conferred cardioprotection by upregulating the cardiac alpha(1)-adrenoceptor and enhancing the effects of stimulation of this adrenoceptor. The effect of testosterone was at least partly mediated by androgen receptors.
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Project description:Nucleotide coenzymes dot the map of metabolic pathways providing energy to drive the reactions of the pathway and play an important role in regulating and controlling energy metabolism through their shared potential energy, which is widely unobserved due to the paradox that the energy in the coenzyme pools cannot be determined from the concentration of the coenzyme couples. The potential energy of the nucleotide couples in the mitochondria or the cytoplasm is expressed in the enzyme reactions in which they take part. The energy in these couples, [NAD+]/[NADH], [NADP+]/[NADPH], [acetyl CoA]/[CoA], and [ATP]/[ADP]x[Pi], regulates energy metabolism. The energy contained in the couples can be altered by suppling energy equivalents in the form of ketones, such as, D-β-hydroxybutyrate to overcome insulin resistance, to restore antioxidants capacity, to form potential treatments for Alzheimer's and Parkinson's diseases, to enhance life span, and to increase physiological performance. © 2019 IUBMB Life, 71(5):565-579, 2019.
| S-EPMC6850382 | biostudies-literature