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Biomedical subjects

Y Touitou

Publications and source records attributed to Y Touitou.

At least 19 recordsLinked to original sources

Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man.

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma patterns of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00-23.00) male students (22.5 +/- 1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux; other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.

Adult

Concurrent adrenocortical carcinoma and Conn's adenoma in a man with primary hyperaldosteronism. In vivo and in vitro studies.

This is a report of a rare and unusual case of adrenal pathology. A patient presented with clinical and biological signs of primary aldosteronism and computed body tomography scan led to our suspecting the presence of a left adrenocortical carcinoma. The in vitro studies performed on the resected tumour showed very low synthesis of mineralocorticoids and glucocorticoids. The patient could not be reexamined until 15 months later, when he still suffered hypertension; another tomography scan revealed a mass on the right adrenal gland. The studies performed on this second tumour confirmed the diagnosis of Conn's adenoma: active in vitro biosynthesis of 18-hydroxy-corticosterone and aldosterone from exogenous tritiated precursors.

Adenoma

The in vitro effect of metyrapone on steroid synthesis in mice adrenals at different circadian stages.

The circadian rhythm of the in vitro biosynthesis of cortisol and cortisone in mice adrenals has been documented in the absence and presence of 0.1 mumol metyrapone, an inhibitor of steroid 11 beta-monooxygenase. After 3 weeks of synchronization with 12 h light:12 h darkness, adrenalectomy was performed at eight circadian stages: 0, 4, 9, 10, 13, 16, 21, and 22 h after light onset (HALO). Because it has been shown that mice adrenals could convert exogenous 11-deoxycortisol, the synthesis of 11-oxysteroids (cortisol+cortisone) in adrenal homogenates was studied from tritiated precursor. The pattern of steroid synthesis showed a maximum around the end (10 HALO) and a minimum at the beginning of the resting period (0 HALO); the variation was approximately 10%. A similar pattern was observed in the presence of a approximately 50% inhibiting dose of metyrapone. On the other hand, the percent inhibition of 11-oxysteroids synthesis was greater at the beginning of the resting period (0 HALO) and minimum around the end of the activity span (21 HALO), with an overall variation of 20%. However, the variations were statistically insignificant (unpaired t test).

Adrenal Glands

Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol.

17-Hydroxyprogesterone is a well-known precursor of androstenedione in adrenal biosynthesis. This study using sheep adrenal incubations demonstrates that 11-deoxycortisol, the precursor of cortisol synthesis, also can be a precursor of androstenedione. Indeed, our data show that androstenedione synthesis is negatively correlated to the synthesis of cortisol and cortisone. This fact allowed us to infer that this new pathway is closely related to the activity of the 11 beta-hydroxylase that is responsible for the synthesis of cortisol. Indeed, when the activity of this enzyme is impaired, 11-deoxycortisol follows the pathway that leads to androstenedione synthesis in the adrenals. This pathway could explain, at least in part, the marked increase of androstenedione observed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

Adrenal Glands

Diurnal changes in psychophysiological variables of school girls: comparison with regard to age and teacher's appreciation of learning.

Ninety-five nonresident girls of a private school volunteered for the study with the teachers' help as well as parental consent. Ages were approximately 8, 9, and 10 years. They were synchronized with diurnal activity from 0730 to 2100 h and nocturnal rest. Fatigue, drowsiness, and attention were self-rated using visual analogue scales; oral temperature was self-measured and a letter cancellation test was performed. Each of these variables was measured at school at 0900, 1100, 1400, and 1600 h on Mondays, Thursdays, Fridays, and Saturdays for two consecutive weeks in 1987 (March 30-April 11) and again in 1989 (March 13-25) when the youngest group had become 10 years old. According to conventional teacher evaluation of learning (learning performance) within each group, three subgroups were formed: top third, middle third, and bottom third. Time series (more than 50,000 data) were analyzed according to several statistical methods, but mainly chronograms with ANOVA. Similar diurnal changes in oral temperature were validated for each group and subgroups. The occurrence of a diurnal change in self-rated variables (fatigue and drowsiness) and score in letter cancellation was age related: no detection in the 8-year-old group (and subgroups) and validation (p less than 0.002) in 9- and 10-year-old groups (and respective subgroups). A good learning performance was associated with a reduced drowsiness in school girls of 9 and 10 years. Age-related, time-of-day differences in drowsiness (when detected) as well as learning performance effect were not associated with observed duration of sleep. Validated changes in self-rated fatigue were close to that of drowsiness. At 0900 h, girls of 9 and 10 years were more tired when belonging to the bottom third than top third subgroup. Whatever the time of day, self-rated attention was greater in the top than in the bottom third for these girls. Differences related to learning performance were validated in each grade. However, best scores were recorded for the bottom third in the 8-year-old group, while best scores were provided by top third subgroups in 10-year-old girls. It seems that in girls around 8 years of age, critical changes can be detected with regard to the (ontogenic?) occurrence of time-of-day differences in a set of psychophysiologic variables as well as influential effects of learning performance on the same variables. Reported finding are compatible with the hypothesis of circadian oscillators working at the level of the cortex of the human brain.

Age Factors

Growth hormone (GH) and GH-releasing hormone response to ACTH 1-17 at different times of day. Evidence of a circadian stage dependence.

The effect of injection of ACTH 1-17 on the secretion of GH has been examined at three different circadian stages (07, 14 and 21 h) in the winter. Each week for six consecutive weeks the subjects were investigated before and after I.M. injection either of saline (controls) or 100 micrograms ACTH 1-17. Each subject was his own control. The peak plasma concentration of GH was always found 40 min after the injection. The larger absolute increase and the greater AUC curve were seen following the injections at 14.00 h and 21.00 h. The findings could not be attributed to an effect on GH-RH, since secretion of it remained unchanged during the test.

Adolescent

Effect of shift work on the night-time secretory patterns of melatonin, prolactin, cortisol and testosterone.

In a study of the internal desynchronization of circadian rhythms in 12 shift workers, 4 of them, aged 25-34 years, agreed to be sampled every 2 h during their night shift (0000 hours to 0800 hours). They were oil refinery operators with a fast rotating shift system (every 3-4 days). We found marked changes in the secretory profiles of melatonin, prolactin and testosterone. Melatonin had higher peak-values resulting in a four-times higher amplitude than in controls. With respect to prolactin and testosterone, peak and trough times were erratic and the serum concentrations were significantly decreased in shift workers. Serum cortisol presented a decreased rhythm amplitude together with higher concentrations at 0000 hours in shift workers. This study clearly shows that fast rotating shift-work modifies peak or trough values and rhythm amplitudes of melatonin, prolactin, testosterone and cortisol without any apparent phase shift of these hormones. Whether the large rhythm amplitude of melatonin may be considered as a marker of tolerance to shift work, as reported for body temperature and hand grip strength, since it would help the subjects to maintain their internal synchronization, needs further investigation.

Adult

Psychophysiological effects of early morning bright light exposure in young adults.

The effects of bright light on circadian rhythms in man are well documented. Nevertheless the theoretical basis and the rules for the practical utilization of light exposure as therapy need still to be better defined. The present study determined to what extent a 2-hr bright light exposure (0500-0700 h) improved the adjustment to an early rising in normal adults. Phase changes were assessed in subjective alertness, performance in several search tasks, time estimation, and a visual discrimination task, as well as in body motility, plasma cortisol concentrations, and body temperature. In comparison with a dim light exposure, the bright light resulted in increased motor activity during waking, in earlier peak of subjective alertness, and an improvement in performance speed in three out of five tasks in the morning. Cortisol and body temperature also were phase-advanced. In summary, light applied to a portion of the circadian cycle sensitive to phase advance shifts influenced rhythms with strong endogenous components (temperature and cortisol), while other rhythms with strong exogenous components were more sensitive to sleep deprivation caused by the early rising time.

Adult

Cortisol and cortisone production in rat and mouse adrenal incubations.

The presence of 17 alpha-hydroxylase in rodent adrenals is debated. The presence in blood of mice of 11-deoxycortisol together with the absence of cortisol is well known. We demonstrated here the in vitro synthesis of 17 alpha-hydroxyprogesterone and cortisol from [3H]progesterone in rat and mouse adrenals. We have shown that these syntheses represented 45 and 28% of those of 11-deoxycorticosterone and corticosterone, respectively, from progesterone. These data clearly suggest the presence of a 17 alpha-hydroxylase activity in vitro in these rodents adrenals. In addition, a noticeable synthesis of cortisol (0.87-1.57% per mg tissue, i.e. 52-64% per incubation flask) from 11-deoxycortisol was also observed and was inhibited by 0.1-0.3 mumol of Metyrapone and SKF 12185. These results allow to underline that the adrenals of rat and mouse, two species commonly used in laboratory experiments, may be used for in vitro investigations on cortisol metabolism from exogenous radioactive precursors.

Adrenal Cortex Hormones

[Legal time shifting and biologic rhythms: summer hour in question?].

In France daylight saving time is set on last sunday of march (legal time becomes GMT + 2 h instead of GMT + 1h) and set off last sunday of september. Fifteen years ago when it was established this change of time was generally welcomed by the public. Since then strong rejection reflexes have appeared and an association against the summer daylight saving time has been founded. The arguments sustained by the oponents to this system are based on economical, agricultural and/or health considerations. A growing number of individuals claim they cannot withstand the change of legal time and suffer from various troubles mainly fatigue and sleep disturbances. An alteration of biologic rhythms has been put forward by some to explain these troubles. We will here discuss the problems related to the change of legal time and especially those in the field of health. For the latter we will show that troubles when they are present can not ascribed to a desynchronization.

Biological Clocks

Circadian and seasonal variations of electrolytes in aging humans.

The circadian and seasonal variations of a set of routinely determined variables (chloride, sodium, potassium, calcium, inorganic phosphorus, magnesium, creatinine, urea and urate) were documented in young men (mean age +/- SD: 24.0 +/- 3.9 yr) and in healthy elderly men (75.3 +/- 6.6) and women (78.2 +/- 9.1). The same urinary variables, except magnesium, were studied in young men. The circadian variability of serum variables was between 2 and 11% except for serum inorganic phosphorus (12-22% according to the group). By contrast, urinary chloride, sodium and potassium revealed large peak-trough differences (55-75%) and the variability of urinary creatinine, urate and urea was also not negligible (20-30%). ANOVA validated seasonal variations for most of the plasma variables and for urinary calcium, phosphorus and uric acid. No age or sex difference in either 24 h means or amplitudes could be observed. These data are of interest for the concept of reference values, for the diagnosis of certain bone and renal disease as well as for chronooptimization in treatment of potential electrolytes deficiency states.

Aged

Lack of effect in vivo of clofibrate on adrenal steroid secretion.

Clofibrate inhibits the synthesis of adrenal steroids when administered in vitro. In the present study the effect in vivo of clofibrate on adrenal steroid secretion has been investigated. Basal levels of plasma progesterone, corticosterone, aldosterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, dehydroepiandrosterone sulphate and dehydroepiandrosterone, and their response to ACTH 1 mg im, were not reduced by chronic administration of clofibrate 2 g per day p.o. for 8 to 34 days to 6 hyperlipidaemic men.

17-alpha-Hydroxyprogesterone

Evidence of 11 beta-hydroxylase deficiency in a patient with cortical adrenal adenoma.

We explored a 61 year old woman with mild hirsutism. An adrenal tumor was found in the left adrenal, which was held responsible for the androgen secretion. The in vitro incubation of the tumor tissue showed an impaired 11 beta-hydroxylation of 11-deoxycortisol. This is a rare and unusual case of adrenal pathology showing that a deficiency in 11 beta-hydroxylase activity does not rule out the presence of an adrenocortical adenoma.

Adenoma