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Biomedical subjects

G Copinschi

Publications and source records attributed to G Copinschi.

At least 19 recordsLinked to original sources
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↗
PubMed1987

Low somatomedin-C (Sm-C) concentrations measured by direct radioimmunoassay in patients with chronic renal failure.

Ten patients suffering from chronic renal failure and undergoing regular hemodialysis were tested immediately before and immediately after a 3-hour dialysis. Serum levels of immunoreactive Sm-C, estimated on unextracted non acidified serum at non equilibrium, were significantly lower than in normal controls and no consistent modifications were observed after dialysis.

Adult↗
PubMed1987

24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment.

Plasma ACTH, cortisol, and GH concentrations were measured at 15-min intervals for 24 h in 11 men suffering from major depressive illness during an acute episode of depression and during clinical remission following antidepressant treatment with either electroconvulsive therapy or amitriptyline. Seven age-matched normal men also were studied. During the acute phase of the illness, the patients had abnormally short rapid eye movement sleep latencies, hypercortisolism, early timing of the nadirs of the ACTH-cortisol rhythms, and shorter nocturnal periods of quiescent cortisol secretion. GH was hypersecreted during wakefulness, and a major pulse occurred before, rather than after, sleep onset. After treatment, rapid eye movement sleep latencies were lengthened, and cortisol levels returned to normal due to a decrease in the magnitude of episodic pulses. Moreover, the timing of the circadian rhythms of ACTH and cortisol as well as the duration of the quiescent period of cortisol secretion were normalized. The amount of GH secreted during wakefulness decreased to normal values, with fewer significant GH pulses. The major elevation of GH secretion in the early part of the night occurred later than that during the depressive episode. These results demonstrate that a disorder of circadian rhythmicity characterizes acute episodes of major depressive illness and that this chronobiological abnormality as well as the hypersecretion of ACTH, cortisol, and GH are state rather than trait dependent.

Adrenocorticotropic Hormone↗
PubMed1986

Somatomedins and steroids.

Somatomedin levels measured by radioreceptor assay, competitive protein-binding assay or radioimmunoassay are normal in hypercortisolism; the decrease of somatomedin activity consistently found in this condition is due to an increase in circulating somatomedin inhibitors resulting in an inhibition of somatomedin action. Progestagens could possibly have a direct stimulatory effect on somatomedin-C (Sm-C) production. During puberty, the increase of Sm-C is correlated with the increase in plasma estradiol and testosterone. In young subjects, relatively low doses of estrogens and of testosterone enhance Sm-C secretion, and in adult menstruating women, a positive relationship is found between testosterone and Sm-C values. An inhibitory effect of estrogens on Sm-C is observed with higher doses and/or in older subjects. Thus, somatomedin levels might be modulated by variations of sex steroids.

Estrogens↗
PubMed1986

Prolonged pulsatile administration of ovine corticotropin-releasing hormone in normal man.

The 24-h profiles of plasma ACTH and cortisol were determined at 15-min intervals in five normal men basally and during iv bolus injections of 25 micrograms ovine corticotropin-releasing hormone (oCRH) every 4 h for 72 h. Each oCRH injection was followed by a distinct elevation of plasma ACTH and cortisol levels, with a return to basal values before the next injection. The characteristics of the ACTH and cortisol pulses induced by 25 micrograms oCRH (i.e. 0.3-0.4 micrograms/kg) were similar to those observed in other studies with 1 microgram/kg human CRH. There was no significant blunting of oCRH-induced hormonal increments in the course of the 72-h study. On each oCRH injection day, the mean 24-h cortisol level was higher than that in the basal study, but there was no increase in the mean 24-h ACTH level. During the 72-h oCRH study, the preinjection ACTH and cortisol levels exhibited a diurnal variation, indicating persistence of the circadian periodicity of pituitary-adrenal activity. There was a diurnal variation of oCRH-induced ACTH increments, with highest responses at 0700 h. A small but not significant reverse trend was apparent for cortisol increments. Spontaneous pulses of ACTH and cortisol occurred throughout the 3 days of oCRH injections, and the total number of spontaneous and oCRH-induced pulses was similar to the number of spontaneous pulses observed in the basal study. All oCRH-induced and more than 90% of spontaneous cortisol pulses occurred concomitantly with an ACTH pulse. The variability of pulse increments was greater for ACTH than for cortisol. In conclusion, prolonged pulsatile administration of oCRH did not induce pituitary desensitization and did not suppress the endogenous circadian and pulsatile ACTH and cortisol variations.

Adrenocorticotropic Hormone↗
PubMed1986

Modulation of immunoreactive somatomedin-C levels by sex steroids.

Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and in progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days -3 to -8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.

Adult↗
PubMed1985

Diurnal hypersecretion of growth hormone in depression.

A 24-h profile of plasma GH concentrations was obtained together with polygraphic recordings of sleep in 16 men suffering from a major depressive disorder (8 unipolar and 8 bipolar) and in 8 age- and sex-matched normal men. None of the patients had any physical illness. All were studied after a drug-free period of at least 15 days. Blood was sampled every 15 min. The amount of GH released in every significant secretory spike was estimated using a computer program. Both unipolar and bipolar depressed patients secreted more GH than normal men (mean +/- SD, 441 +/- 189 micrograms/24 h for unipolar depressed men; 357 +/- 143 micrograms/24 h for bipolar depressed men vs. 172 +/- 101 micrograms/24 h for normal men (P less than 0.01). This hypersecretion occurred during waking hours rather than during sleep. The increase in daytime GH release was more marked in unipolar depressed patients. During sleep, depressed patients and normal men secreted similar amounts of GH despite an overall reduction in slow wave stages in depressed patients. An early sleep GH increase was found in all but one of the normal men, but was absent in seven of the eight unipolar depressed patients, who had, instead, a presleep increase in between 2100-0000 h. No consistent disturbance of the temporal association between sleep onset and GH secretion was found in bipolar depressed patients.

Adult↗
PubMed1985

The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness.

The 24-h profile of plasma ACTH and cortisol levels was determined in 18 men suffering from major depressive illness (8 with unipolar depression and 10 with bipolar depression) as well as in 7 age-matched normal men. Blood was sampled every 15 min. The circadian variation and episodic fluctuations were analyzed for each individual profile. Both unipolar and bipolar depressed patients had higher 24-h mean cortisol levels (P less than 0.01) than normal men, but no significant difference in 24-h mean ACTH level was found. The nadir of cortisol secretion occurred almost 3 h earlier in older normal subjects and patients with unipolar depression, regardless of age, than in younger normal subjects. This shift paralleled a similar advance of the ACTH nadir. Early timing of the quiescent period of ACTH-cortisol secretion was also found in several patients with bipolar depression, but did not reach significance at the group level. The hypercortisolism in the depressed patients was associated with an increase in the magnitude, but not the number, of cortisol secretory episodes. About 90% of the cortisol pulses could be related to a concomitant ACTH pulse in normal subjects as well as in both groups of depressed patients. However, concomitant ACTH and cortisol pulses were less correlated in magnitude in depressed patients than in normal subjects. These results indicate that major depressive illness is associated with disturbances of pituitary-adrenal function. The early timing of the nadir of ACTH-cortisol secretion suggests that disorders of circadian time keeping may characterize major endogenous depression.

Adrenocorticotropic Hormone↗