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Biomedical subjects

G Copinschi

Publications and source records attributed to G Copinschi.

At least 19 recordsLinked to original sources
PubMed1995

Effects of bedtime administration of zolpidem on circadian and sleep-related hormonal profiles in normal women.

Short-acting benzodiazepine hypnotics may phase-shift circadian rhythms and improve adaptation of sleep patterns to abrupt time shifts, depending on the timing of administration. The aim of the present study was to determine whether bedtime administration of zolpidem, a non-benzodiazepine hypnotic, causes alterations in circadian rhythmicity or in the normal interactions between sleep and hormones. Eight normal women (aged 21-33 years) each participated in a baseline study and a study with zolpidem administration. On each occasion, blood samples were obtained at 20-minute intervals for 25 hours, starting at 1000 hours. Zolpidem (10 mg) was given orally at 2245 hours. Zolpidem administration was associated with an increase in stages III + IV sleep. Cortisol, melatonin, thyrotropin and growth hormone profiles were similar in both experimental conditions. In contrast, though remaining in the normal range, the nocturnal elevation of prolactin was enhanced two-fold in all subjects after zolpidem during early sleep, and prolactin levels were still 50% higher than baseline in late sleep. Morning levels were similar in both studies. In conclusion, bedtime administration of 10 mg zolpidem, a standard clinical dosage, systematically induces a transient moderate hyperprolactinemia, but does not alter other sleep-related hormonal secretions or endocrine markers of circadian rhythmicity.

Adult↗
PubMed1995

Effects of ageing on modulation of hormonal secretions by sleep and circadian rhythmicity.

Circadian rhythmicity persists in healthy elderly subjects but a number of 24 hour rhythms are dampened and/or advanced in old age. The tendency for earlier sleep onset, earlier morning awakening and a more fragmented and more shallow sleep period is representative of these alterations. Other overt rhythms which have been shown to be of lower amplitude and/or phase-advanced are those of body temperature and of the peripheral levels of hormones such as cortisol, melatonin, TSH, testosterone, prolactin and GH. Mean hormonal levels are generally decreased, but overall cortisol secretion is increased with ageing. These modifications are likely to be partially due to alterations of the circadian central nervous system processes controlling circadian rhythmicity and sleep.

Aging↗
PubMed1994

The 24-hour profiles of cortisol, prolactin, and growth hormone secretion in mania.

OBJECTIVE: To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania. METHODS: Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specifically designed computer algorithms. RESULTS: The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal. CONCLUSION: The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression.

Acute Disease↗
PubMed1994

Regulation of maternal insulin-like growth factor I by placental growth hormone in pregnancy. Possible action of maternal IGF-I on fetal growth.

In normal and in pathological human pregnancies, a specific placental growth hormone variant, rather than placental lactogen, substitutes for the suppressed pituitary GH to stimulate the maternal insulin-like growth factor I (IGF-I). In pathological pregnancies with disorders of the feto-placental unit, low levels of placental GH hormone result in relatively low levels of maternal IGF-I. In normal pregnancies, the baby birth weight is positively correlated with maternal IGF-I values.

Birth Weight↗
PubMed1993

Insulin-like growth factor I values in patients on maintenance hemodialysis: relationship to growth hormone and albumin levels.

Twenty-seven uremic patients (blood urea: 58.2 +/- 2.2 mmol/l; blood creatinine: 1,069 +/- 53 mumol/l; mean +/- SE) on maintenance dialysis were investigated immediately before and after a dialysis session. Control data were obtained from 30 normal volunteers. Before dialysis, circulating levels of insulin-like growth factor I (IGF-I) were similar in anuric and nonanuric patients, averaging 305 +/- 24 micrograms/l, a value not different from that observed in normal controls (262 +/- 16 micrograms/l). IGF-I levels were not modified by dialysis. In contrast, GH values were significantly higher in uremic patients (3.6 +/- 0.6 microgram/l) than in normal controls (2.5 +/- 0.5 microgram/l) and decreased significantly after the dialysis session (0.8 +/- 0.1 microgram/l). IGF-I values were positively correlated with GH and albumin, but not with the various parameters of renal insufficiency, suggesting that in chronic renal failure, synthesis of IGF-I appears to be regulated, as in normal subjects, by growth hormone and nutritional status.

Adult↗
PubMed1993

Sleep-promoting effects of growth hormone-releasing hormone in normal men.

Growth hormone-releasing hormone (GHRH) promotes rapid-eye-movement (REM) and non-REM sleep in animals, but there is little direct evidence for a hypnogenic action of GHRH in humans. In the present study, the possible somnogenic effects of intravenous bolus injections of a dose of GHRH eliciting physiological elevations of GH secretion in healthy young men were investigated. GHRH (0.3 micrograms/kg body wt) was given in early sleep [i.e., 1st slow-wave (SW) period], late sleep (i.e., 3rd REM period), and early sleep after sleep deprivation until 0400 h (i.e., 1st SW period). In the absence of sleep deprivation, injection of GHRH in early sleep did not modify SW sleep but increased REM sleep. GHRH administration in the third REM period was followed by a marked decrease of wake and an almost 10-fold increase in SW sleep. When GHRH was administered during the first SW period after sleep deprivation until 0400 h, the duration of wake decreased. Thus GHRH has sleep-promoting effects in young adults, particularly when given at a time of decreased sleep propensity.

Adult↗
PubMed1993

Regulation of maternal IGF-I by placental GH in normal and abnormal human pregnancies.

Throughout gestation, maternal insulin-like growth factor I (IGF-I) increases progressively despite suppressed pituitary growth hormone (GH) secretion. We have previously shown that in normal pregnancy, a specific placental GH variant, rather than human placental lactogen (hPL), substitutes for pituitary GH in the regulation of maternal IGF-I. We studied the maternal IGF-I secretion in a cohort of 286 normal and abnormal pregnancies (617 blood samples). Regardless of pathology and gestational age, IGF-I values correlated with corresponding placental GH but not with hPL values. Similar correlations were evidenced for each 2-wk gestational period between 32 and 39 wk. In pathological pregnancies, when only those hormonal results that are obtained before any treatment are considered and diabetes is excluded, IGF-I levels were closely related to corresponding placental GH, but not to hPL. In women with a fetoplacental unit disorder, low placental GH levels resulted in low IGF-I and in a secondary pituitary GH increase, whereas in patients without detectable impairment of the fetoplacental unit normal placental GH corresponded to normal IGF-I. These results suggest that in pathological as well as in normal pregnancy, placental GH, and not hPL, substitutes for pituitary GH to regulate the maternal IGF-I secretion.

Adolescent↗
PubMed1992

A quantitative estimation of growth hormone secretion in normal man: reproducibility and relation to sleep and time of day.

Recent reports, based on measurements of plasma GH levels, have challenged the concept that GH secretion is dependent on sleep and not modulated by circadian rythmicity. Because plasma levels reflect not only the secretory process, but also the effects of distribution and degradation, temporal limits of active secretion and, consequently, synchrony with other physiological events cannot be accurately estimated from circulating concentrations. The present study was undertaken to examine the roles of sleep and time of day in modulating pulsatile GH secretion, using a mathematical procedure (deconvolution) allowing secretory rates to be estimated from peripheral levels. Eight young nonobese healthy men participated each in six separate 16-h studies involving either normal or delayed sleep. Plasma GH levels were measured at 15-min intervals, and GH secretory rates were calculated by deconvolution. Each individual study was preceded by one night of habituation, and sleep was polygraphically recorded in all studies. Repeated measurements of plasma insulin-like growth factor-I (IGF-I) were performed in all subjects. Deconvolution revealed the existence of approximately 20% more GH pulses than detected in the plasma profiles. Large peaks of plasma GH concentrations often reflected the occurrence of a succession of secretory pulses. The total amount of GH secreted varied 10-fold across individual studies, but the within-subject variability (32%) was less than half the across-subject variability (65%). IGF-I levels were also more reproducible for a given subject than across subjects (11% vs. 36% variability) and did not correlate with the amount of GH secreted. During normal waking hours, the GH secretory rate was similar in the evening and the morning. This secretory rate was doubled during wakefulness at times of habitual sleep and tripled during sleep, even when sleep was delayed until 0400 h. A pulse starting within 30 min after sleep onset was present in all profiles with normal sleep and in 13 of 16 profiles with delayed sleep. The amount of GH secreted in response to sleep onset was tightly correlated with the level of secretion during wakefulness (r = 0.92). Almost 70% (57 of 83) of the pulses occurring during sleep were associated with slow wave (SW) stages. The amount of GH secreted in SW-associated pulses was correlated with the amount of SW occurring during the pulse, even when sleep-onset pulses were not considered. We conclude that in normal adult men, the amount of GH secretion and the levels of IGF-I are more reproducible within than across individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Sleep, awakenings, and insulin-like growth factor-I modulate the growth hormone (GH) secretory response to GH-releasing hormone.

To delineate possible factors influencing the magnitude of the GH response to GH-releasing hormone (GHRH), eight young healthy men participated in seven 16-h studies involving saline infusions or injections of 0.3 micrograms/kg GHRH at various times of day and stages of sleep. GH responses were quantified by deconvolution, a procedure allowing for secretory rates to be estimated from peripheral levels. While the plasma responses were monophasic, deconvolution revealed that the secretory response to GHRH generally included several distinct bursts in rapid succession. The intersubject variability of GH responses was very wide, but for a given subject, the response was quite reproducible (mean +/- SEM coefficient of variation, 21 +/- 3%). When GHRH was given during the waking period, the magnitude of the response was directly related to the amount of spontaneous GH secretion, negatively correlated with circulating levels of insulin-like growth factor-I (IGF-I) and was not influenced by time of day. When GHRH was given during slow wave sleep, the magnitude of the response was enhanced. When GHRH was given during rapid eye movement sleep, the response was similar to that observed during wake. Awakenings during sleep consistently inhibited the secretory response to GHRH, and resumption of sleep was associated with a reappearance of the secretory process. Thus, in normal men of similar age and body weight, the GH response to GHRH is dependent on the sleep or wake condition, circulating levels of IGF-I, and, possibly, genetic and lifestyle factors.

Adult↗
PubMed1991

Circadian and sleep-related endocrine rhythms in schizophrenia.

Plasma levels of prolactin, growth hormone, corticotropin, and cortisol were measured at 15-minute intervals for 24 hours in nine unmedicated male schizophrenic patients and in nine age-matched normal male subjects. Each study was preceded by 3 days of habituation to the laboratory environment. Sleep was polygraphically recorded. The circadian and pulsatile variations present in each hormonal profile were quantitatively characterized with the use of computer algorithms specifically designed for analyses of hormonal fluctuations. The major abnormality of neuroendocrine release that was observed in the schizophrenic patients was an almost threefold enhancement of the sleep-related increase in the prolactin level, associated with an intensified frequency of nocturnal prolactin pulses. This increased stimulatory effect of sleep on prolactin secretion was evident immediately after sleep onset. The normal inhibition of cortisol secretion during early sleep was absent in schizophrenic patients. The major sleep abnormalities were a prolonged sleep latency and a reduction in total rapid eye movement stage sleep. During wakefulness, prolactin and cortisol levels were normal. The 24-hour profile of growth hormone was unaltered in schizophrenic patients, and a sleep-onset growth hormone pulse was observed in all patients. No abnormalities were noted in the levels or temporal organization of corticotropin secretion. Both the amplitude and the timing of the cortisol rhythm were normal. We conclude that, in schizophrenic men, pituitary-adrenal function and circadian time-keeping are normal but prolactin secretion is hyperresponsive to the physiologic stimulus of sleep onset. Schizophrenia thus appears to be characterized by a subset of neuroendocrine disturbances distinct from that observed in major endogenous depression.

Adrenocorticotropic Hormone↗
PubMed1991

Insulin-like growth factor I: a good indicator of functional hepatocellular capacity in alcoholic liver cirrhosis.

To assess the value of serum insulin-like growth factor I (IGF-I) determination in liver disease, 21 patients hospitalized for active alcoholic cirrhosis (19 males, 2 females), 56 +/- 2 y (mean +/- SE) were studied at admission. Individual scores of hepatic alterations (Child score) ranged from 6 to 12 (mean: 9 +/- 1). Basal IGF-I levels were dramatically decreased, averaging 0.11 +/- 0.02 U/ml vs 0.70 +/- 0.08 U/ml in 15 control subjects. In cirrhotic patients, IGF-I values were inversely correlated with the modified Child index (r = 0.57, p less than 0.01). A highly significant positive correlation (r = 0.68, p less than 0.001) was evidenced between IGF-I levels and aminopyrine breath test values (which provide quantitative estimates of the hepatic functional capacity). In contrast, no significant relationship was found between IGF-I levels and various nutritional parameters (albumin, prealbumin, retinol binding protein) after partial correlation analysis. The present data suggest that, in alcoholic cirrhosis, the decrease of circulating IGF-I values is mainly related to alterations of liver function, and that IGF-I can be used as a good indicator of functional hepatocellular capacity.

Adult↗
PubMed1991

Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes.

To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period. The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism. In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum. Elevated levels persisted until noon. The morning glucose maximum corresponded to a relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and 13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05). In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes. In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates. Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P less than 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression. In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise. GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P less than 0.01). Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period. We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.

Adult↗
PubMed1990

Physiological role of somatostatin on growth hormone regulation in humans.

Growth hormone (GH) secretion in man is pulsatile and this pattern is regulated by both GH-releasing hormone (GHRH) and somatostatin. A large body of experimental evidence in both man and animals supports the model that bursts of GH secretion are mediated by a reduction of tonic hypothalamic somatostatin secretion. Our studies have been performed in normal subjects with frequent blood sampling for GH measurements (from 20-minute to 30-second intervals); the data have been analyzed by computer algorithms to objectively determine pulse characteristics and, in some studies, to estimate both pituitary secretion and clearance rates using deconvolution analysis. The studies include profiles of GH secretion in normal men and women in fed and fasted states; analysis of GH secretion during sleep; and administration of GHRH during different stages of sleep and after sleep deprivation. The variable GH response to exogenous GHRH and the attenuated response after 6 hours of GHRH infusion to GHRH, while not to hypoglycemia, as well as the pulsatile profile of GH secretion in response to continuous GHRH infusions (24 hours to 14 days), all support the thesis that it is hypothalamic somatostatin that determines the timing of bursts of GH secretion. This is further confirmed by the profile of GH secretion in a patient with ectopic GHRH secretion. Recently, we have initiated studies with the novel synthetic GH releasing hexapeptide, HisDTrpAlaTrpDPheLysNH2 (GHRP). Our studies show that it acts synergistically with GHRH. Several lines of evidence suggest that GHRP stimulates GH secretion independently of GHRH receptors and acts at both the hypothalamic and pituitary levels. It may act to functionally antagonize somatostatin.

Amino Acid Sequence↗
PubMed1990

Placental growth hormone as a potential regulator of maternal IGF-I during human pregnancy.

Ninety-three healthy women were investigated during normal pregnancy, and 177 blood samples were obtained at various gestational stages. In 8 of the women, serial measurements were obtained over a period of 16-34 wk from 8 to 40 wk of gestation. In 13 women, daily blood samples were obtained from day 0 to day 6 after delivery. Insulin-like growth factor I (IGF-I) and human placental lactogen (hPL) were measured by radioimmunoassays. Growth hormone (GH) was estimated by two monoclonal antibody-based radioimmunoassays insensitive to physiological concentrations of hPL: the K24 assay, which recognizes only pituitary hGH, and the 5B4 assay, which reacts with all the known pituitary as well as placental GH variants. Placental GH was distinguished from the main pituitary variant through its specific immunoreactivity pattern. Mean plasma levels of IGF-I were relatively stable until 29-30 wk gestation, then increased progressively to reach a maximum at 35-36 wk. Regardless of gestational age, individual IGF-I values exhibited a highly significant positive correlation with placental GH, reflected by 5B4 immunoreactivity, whereas the correlation between IGF-I and hPL was not statistically significant. Considering each 2-wk gestational period separately, we found a positive correlation between IGF-I and 5B4 hGH at 31-32 wk. Conversely, no evidence of correlation was found between IGF-I and hPL at any period. After delivery, IGF-I evolution exhibited a biphasic pattern, with an initial decrease to low values followed by a progressive return toward levels found in nonpregnant healthy women. These results strengthen our previous hypothesis that placental growth hormone is involved in the control mechanism of serum IGF-I levels in normal pregnant women.

Antibodies, Monoclonal↗
PubMed1990

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.

Animals↗
PubMed1988

[Neuroendocrine rhythms in uni- and bipolar depressions].

Eighteen patients with major depressive disorder of the endogenous subtype (8 unipolars and 10 bipolars) were submitted to blood sampling at 15 min interval for 24 h with polygraphic sleep recording during an acute episode of depression. Plasma growth hormone (GH), adrenocorticotrophin (ACTH) and cortisol were measured in each sample. The depressed patients hypersecreted GH during the daytime and had hypercortisolism which was evident throughout the 24 h span. The nadir of ACTH and cortisol rhythms was advanced by an average of 3 h as compared to the timing observed in normal subjects. These abnormalities were more pronounced and more consistent in patients with unipolar rather than bipolar depression. These results are consistent with the hypothesis that disorders of circadian time-keeping may characterize major endogenous depression.

Adrenal Cortex Hormones↗