Biomedical subjects
H Oftebro
Publications and source records attributed to H Oftebro.
Evaluating an abnormal urinary steroid profile.
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Detection of testosterone administration by increased ratio between serum concentrations of testosterone and 17 alpha-hydroxyprogesterone.
An increased ratio between urinary testosterone (T) and epitestosterone (epiT) has been accepted by the International Olympic Committee as a marker for T doping. However, in a few subjects, we and others have observed constantly above-normal urinary T/epiT ratios that are unlikely to be related to exogenous T administration. To find a better test for T doping, we studied several serum and urinary androgens and androgen precursors, estrogens, and luteinizing hormone (LH) in seven healthy volunteers for 35 days after an intramuscular injection of 250 mg of testosterone enanthate. Among urinary analyses, only the T/epiT ratio was a suitable marker of T doping; of the serum assays, 17 alpha-hydroxyprogesterone (17OHP), T/17OHP ratio, LH, and T/LH ratio were fair to good markers of T doping. The serum T/17OHP ratio was the best marker of those tested, with all seven subjects having above-normal values for this in the first 3 days of the observation period. No other marker showed abnormal values in all subjects at any time. Moreover, the T/17OHP ratio was affected by neither diurnal variation nor physical stress. The value of this marker for T doping was further supported by the finding of normal T/17OHP ratios in a subject with increased urinary T/epiT ratios caused by an abnormally low testicular epiT production, probably related to genetic factors.
Comparison of changes in testosterone concentrations after strength and endurance exercise in well trained men.
Changes in the testosterone concentrations after single sessions of endurance and strength training were measured in seven well trained men, experienced in both forms of training. Both training sessions were rated as hard to very hard on the Borg scale. Blood samples for testosterone measurements were taken before, immediately after, and 2, 4 and 6 h after the training sessions as well as the next morning. The mean testosterone concentration increased 27% (P less than 0.02) and 37% (P less than 0.02) during the strength and endurance training session, respectively. Two hours after the training sessions the mean testosterone concentration had returned to the pre-training level and remained at that level for the length of the observation period. There were no significant differences in the changes in testosterone concentration after strength and endurance training but there were large differences in the testosterone response at the level of the individual. A high correlation (r = 0.98; P less than 0.001) for individuals was found between increases in testosterone concentration after strength and after endurance training. It was concluded that the changes in mean testosterone values followed the same timecourse after single sessions of strength and endurance training of the same duration and perceived exertion. The interindividual differences in testosterone response may be of importance for individual adaptation to training.
Athletics and doping--effects on clinical laboratory analyses.
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Reconstitution of C27-steroid 26-hydroxylase activity from bovine brain mitochondria.
We have previously demonstrated the presence of cytochrome P-450 in a soluble preparation of bovine brain mitochondria (Oftebro, H., Størmer, F.C., and Pedersen, J.I. (1979) J. Biol. Chem. 254, 4331). In the present work we show that this preparation, in the presence of NADPH, adrenodoxin and adrenodoxin reductase catalyzes omega-hydroxylation of a number of C27-steroids that are intermediates in bile acid biosynthesis. The rates of hydroxylation were 1-2 order of magnitudes lower than reported for similar preparations from rat and human liver. No significant activity was detected with cholesterol as substrate. The physiological significance of brain mitochondrial cytochrome P-450 is discussed.
Validation of a radioreceptor assay for 1,25-dihydroxyvitamin D using selected ion monitoring GC-MS.
This report describes two methods for the measurement of 1,25-dihydroxyvitamin D [1,25(OH)2D] in serum: A modified radio receptor assay (RRA), employing a 1,25(OH)2D receptor from calf thymus, and selected ion monitoring (SIM) with combined capillary gas chromatography (GC)-mass spectrometry (MS). The intra-assay coefficient of variation was close to 13% for both methods, and the inter-assay coefficients of variation were 14.0 and 6.5% for RRA and SIM (GC-MS), respectively. Aliquots of 2 ml (RRA) and 20 ml (SIM) serum were used, and the limits of detection were 10 and 6 pmol/l, respectively. The analytical recovery of each method was assessed, and a maximum deviation from the expected value of 10 and 2% was found for RRA and SIM, respectively. A correlation coefficient of 0.93 (slope 0.97) was obtained when 27 different serum samples were analyzed by both methods. Included in this study were serum samples from healthy subjects and patients with subnormal as well as supranormal 1,25(OH)2D levels. This result showed that the RRA accurately measured the serum levels of 1,25(OH)2D and therefore should be useful in the diagnosis and control of vitamin D dependent diseases.
Biochemical changes and endocrine responses in cystic fibrosis in relation to incremental maximal exhaustive exercise.
The purpose of this study was to compare biochemical changes and endocrine responses during an incremental maximal bicycle test in three well-trained 18-year-old patients with cystic fibrosis (CF) and in three healthy controls. Although the blood concentration at rest of the white cell count, haptoglobin, phosphorus, urea, creatinine, and uric acid were somewhat different in the two groups, the CF patients had similar biochemical changes in response to the exercise compared with the healthy men. The endocrine responses to exercise seemed to be different between the two groups with regard to changes in cortisol, growth hormone, and testosterone concentrations. The differences, however, were probably caused by differences in age, training situation, and psychological stress reaction rather than by pathological mechanisms.
Biochemical changes and endocrine responses in cystic fibrosis in relation to a marathon race.
Biochemical changes and endocrine responses during the New York Marathon (42195 m) were investigated in three 18-year-old male adolescents with cystic fibrosis (CF) and three healthy men who accompanied the CFs during the race. The ambient temperature was 20 degrees-28 degrees C and the relative humidity 98%-75% during the run. The CF patients, who had Shwachman scores of 60, 85 and 95 completed the run without major problems in 6.10, 4.42, and 4.32 h, respectively. Serum concentrations of Na and Cl decreased slightly, but the values were still within normal range. Na and Cl excretions in the urine decreased to very low levels in the CF adolescents during the run. All the other biochemical changes were similar to the changes in the controls. Aldosterone concentration increased to a higher level and maintained this increase for a longer time after the race in the CFs. Testosterone concentration decreased more in the CFs during the race compared with the controls. Growth hormone concentration showed individually varying changes in response to the exercise. This study demonstrates that patients with CF may participate in strenuous prolonged exercise even in humid and hot conditions, without untoward effects. The observed differences in hormonal responses to exercise might be explained by differences in age, training status, and relative exercise intensity rather than by hormonal or other disturbances in CF.
Vigorous exercise in a female with cystic fibrosis: spirometric, biochemical, and endocrine responses during four types of intensive exercise.
Spirometric, biochemical, and endocrine responses during a maximal ergometer cycle test and during three runs (10 km, 21.1 km, and 42.2 km) were investigated in one female with cystic fibrosis (CF) 27 years of age and in two healthy control females 26 and 29 years of age. One of the controls ran as a companion to the CF woman, while the other ran at her own speed. The CF woman has a chronic respiratory Pseudomonas aeruginosa infection, and her spirometric values were 50%-70% of predicted values at the time of the study. For the last years she has been training almost daily with aerobics, running, cycling, or skiing. She completed the four types of exercise without major problems. Her spirometric values increased transiently following the cycle test and for several hours following the three races (maximal 20%-30% increase of spirometric values), while the controls had transient decreases of the same variables in response to the runs. The biochemical and the hormonal changes were similar in the CF woman and the control who ran at her own speed, while the control who was a less stressed companion showed smaller changes. This study demonstrates that well-trained females with CF may participate in strenuous prolonged exercise without untoward effects.
Calcium status and calcium-regulating hormones in alcoholics.
To elucidate effects of chronic ethanol consumption on clinical chemical parameters reflecting overall calcium homeostasis 34 hospitalized male alcoholics and 35 age-matched controls were studied during the winter season. Serum concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were reduced by 28% (p less than 0.01) and 24% (p less than 0.02) among the alcoholics as compared to the controls, respectively. Dietary intake of vitamin D3 did not differ significantly between the groups. The calcium level was below lower limit of reference in nine alcoholics (26%). Serum concentrations of parathyroid hormone and phosphorus were within normal ranges in both groups, and no differences were observed in levels of magnesium, vitamin D-binding protein, calcitonin, or alkaline phosphatase. In conclusion, it is possible that the activities of enzymes crucial in vitamin D3 metabolism may be altered in alcoholics.
Early postmenopausal bone loss is not associated with a decrease in circulating levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or vitamin D-binding protein.
To study changes in the rate of bone loss before and after the menopause, 19 normal premenopausal women of the same age were followed with annual measurements of appendicular bone mass for 8 yr. Their serum estrone, estradiol, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and vitamin D-binding protein levels also were measured annually. The serum estrogen levels declined before the menopause, and the rate of bone loss more than doubled at the time of the menopause. There were no significant changes in the serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin LD or vitamin D-binding protein levels from the pre- to the postmenopausal period. We conclude that changes in vitamin D metabolite levels are not associated with early postmenopausal bone loss.
The presence of an adrenodoxin-like ferredoxin and cytochrome P-450 in brain mitochondria.
An iron-sulfur protein has been isolated from bovine brain mitochondria and purified 200-fold. The optical spectrum (peaks at 412 and 455 nm which disappear upon reduction) and the EPR spectrum (g values at 1.94 and 2.02) were typical for a ferredoxin. In reconstitution experiments, the protein could replace adrenodoxin in the cholesterol side chain cleavage reaction. The additional detection of cytochrome P-450 in brain mitochondria indicates that the isolated ferredoxin is part of a cytochrome P-450-dependent hydroxylation system.
Isolation from bovine liver mitochondria of a soluble ferredoxin active in a reconstituted steroid hydroxylation reaction.
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