Biomedical subjects

A Caufriez

Publications and source records attributed to A Caufriez.

At least 19 recordsLinked to original sources

PubMed1997

The pubertal spurt: effects of sex steroids on growth hormone and insulin-like growth factor I.

In puberty, the growth spurt and the appearance of secondary sex characteristics occur concomitantly with an increase of sex steroids, growth hormone (GH) and insulin-like growth factor I (IGF-I). A number of experiments indicate that sex steroids exert a stimulatory action on the somatotropic axis. This effect is due to an amplifying action of oestradiol (secreted by the ovaries or after testosterone aromatization) on the neuroendocrine regulation of pulsatile GH release.

Estradiol↗

PubMed1997

Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.

Previous studies have indicated the existence of common mechanisms regulating sleep and somatotropic activity. In the present study, we investigated the effects of prolonged treatment with a novel, orally active, growth hormone secretagogue (MK-677) on sleep quality in healthy young and older adults. Eight young subjects (18-30 years) followed a double-blind, placebo-controlled, three-period crossover design. Each subject participated in three 7-day treatment periods (with bedtime drug administration), presented in random (Latin square) order, and separated by at least 14 days. Doses were 5 and 25 mg MK-677 and matching placebo. Six older subjects, ages 65-71 years, each participated in two 14-day treatment periods (with bedtime drug administration) separated by a 14-day washout. Doses were 2 and 25 mg MK-677 during the first and second periods, respectively. Baseline sleep and hormonal data were obtained on the 2 days preceding the beginning of the first 14-day treatment period. In young subjects, high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV and in a more than 20% increase in REM sleep as compared to placebo (p < 0.05). The frequency of deviations from normal sleep decreased from 42% under placebo to 8% under high-dose MK-677 (p < 0.03). In older adults, treatment with MK-677 was associated with a nearly 50% increase in REM sleep (p < 0.05) and a decrease in REM latency (p < 0.02). The frequency of deviations from normal sleep also decreased (p < 0.02). The present findings suggest that MK-677 may simultaneously improve sleep quality and correct the relative hyposomatotropism of senescence.

Adolescent↗

PubMed1996

Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men.

To assess the effects of prolonged administration of a novel analog of GH-releasing peptide (MK-677), nine healthy young men participated in a randomized, double blind, three-period cross-over comparison of orally administered placebo and 5- and 25-mg doses of MK-677. Each period involved bedtime administration of the drug for 7 consecutive days. At the end of each period, plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured at 0745 h, and 24-h profiles of plasma GH and cortisol were obtained at 15-min intervals together with the 24-h urinary excretion of free cortisol. Profiles of plasma free cortisol were calculated at hourly intervals. The amounts of GH secreted were similar in all three conditions, but GH pulse frequency was increased with both dosages of the drug, primarily because of an increase in the number of low amplitude pulses. Plasma IGF-I levels were increased in a dose-dependent manner, whereas IGFBP-3 levels were increased only with the highest dosage. There was a positive relationship between GH pulse frequency and IGF-I increase. Except for an advance in the nocturnal nadir and in the morning elevation, MK-677 had no effect on cortisol profiles. In particular, 24-h mean levels of plasma total and free cortisol and urinary excretion of free cortisol were similar under all conditions. The present data suggest that the use of MK-677 for the treatment of relative somatotropic deficiency, particularly in older adults compromised by such deficiency, deserves further investigation.

Administration, Oral↗

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↗

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

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

Choice of parameter for expressing bone mineralization.

In this cross-sectional study, the relative importance of anthropometric factors and that of biological parameters on bone mineralization were evaluated and their practical implications inferred on the choice of the parameter to be used for the estimation of bone mineralization. A close relationship between anthropometric factors and bone mineral content (BMC) was observed and this relationship was shown to be independent of age. Furthermore, by regression analyses, anthropometric parameters appeared to explain a large part of the variance in BMC and preceded the hormonal parameters in the stepwise analysis of this model. Using bone mineral density (BMD) data, however, we observed a weaker relationship between anthropometric factors and bone mineralization and a relatively stronger relationship between steroid hormones and bone mineralization than those observed using the BMC data. Furthermore, by multiple regression analysis the hormonal factors preceded the anthropometric parameters in the stepwise analysis of the model. As strong epidemiological and clinical evidence exists on the relationship between steroid hormones and bone loss, these results constitute a supplementary argument for the use of BMD for the estimation of bone mineralization.

Adult↗

PubMed1991

Menstrual disorders in adolescence: pathophysiology and treatment.

Menstrual problems including amenorrhea, oligomenorrhea, irregular cycles, abnormal uterine bleeding or dysmenorrhea represent 50% of adolescents' gynecologic complaints. Irregular and anovulatory cycles are common during the first postmenarcheal years and may reflect a normal transient step of ovarian hyperandrogenism, but they may also result from hormonal abnormalities affecting the adrenals, the ovaries or the pituitary. Amenorrhea may be a sign of late puberty or of a problem affecting the hypothalamus, the pituitary or the ovaries. Evaluation includes a complete physical examination, basal hormonal determinations of the hypothalamic-pituitary-ovarian function, of the thyroid, of the androgens and of the nutritional and growth parameters. This first evaluation must be completed by a karyotype analysis in case of primary amenorrhea or by the measurements of free testosterone, androstanediol glucuronide and testosterone glucuronide in case of hirsutism, and may be followed by X-rays, echography or dynamic tests depending on the first results. Therapy will always be directed towards the etiology of the disease. Abnormal uterine bleeding is generally the result of anovulatory cycles and responds to hormonal therapy, but a systemic illness, a local pathology or a complicated pregnancy must always be excluded. In case of dysmenorrhea, endometriosis must be excluded. Simple dysmenorrhea is generally suppressed by antiprostaglandins.

Adolescent↗

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

Serum levels of gonadotrophins and steroid hormones in the post-menopause and later life.

Changes in the serum levels of gonadotrophins and steroid hormones with increasing age were studied in 449 women aged 40 and over to investigate the relationships between these hormones even very late in life. The levels of oestradiol (E2) and dehydroepiandrosterone sulphate (DHEA-S) fell after age 50 and remained low thereafter. However, while serum oestrone (E1), testosterone (T), delta-4-androstenedione (A) and prolactin (PRL) concentrations also decreased initially after age 50 they subsequently rose again progressively and this increase was in fact significant in the case of E1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rose after age 50, but whereas FSH remained elevated, LH decreased late in life. Cortisol (F) increased significantly after age 70. There was a significant correlation between androgens and E1 as well as between E2 and LH, even after age 60. Owing to the great heterogeneity of the population studied, it is not yet possible to speculate as to the physiopathological significance of these observations. It would seem, however, that the negative feedback effect of oestrogens on LH secretion remains operational very late in life.

Aged↗

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↗

PubMed1986

Male pseudohermaphroditism due to 17-ketoreductase deficiency: report of a case without gynecomastia and without vaginal pouch.

A black adult subject, exhibiting complete virilization at puberty with psychological female orientation, was investigated. An older sister had similar physical habitus. Hormonal data showed an androstenedione/testosterone ratio greater than 1. This led us to the diagnosis of 17-ketoreductase deficiency, with possible genetic transmission of the defect.

17-Hydroxysteroid Dehydrogenases↗