Anne Caufriez

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.

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

To assess the value of serum insulinlike 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 < 0.01). A highly significant positive correlation (r = 0.68, p < 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.

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.

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.

A potential role of endogenous progesterone in modulation of GH, prolactin and thyrotrophin secretion during normal menstrual cycle

Objective  Previous studies investigating the fluctuations of endocrine secretion across the menstrual cycle yielded inconsistent results. Our objective was to evaluate during the menstrual cycle the potential role of endogenous oestradiol and progesterone in the regulation of hormones primarily controlled by the circadian clock and/or the sleep‐wake cycle.

Sleep and Hormonal Changes in Aging

Age-related sleep and endocrinometabolic alterations frequently interact with each other. For many hormones, sleep curtailment in young healthy subjects results in alterations strikingly similar to those observed in healthy old subjects not submitted to sleep restriction. Thus, recurrent sleep restriction, which is currently experienced by a substantial and rapidly growing proportion of children and young adults, might contribute to accelerate the senescence of endocrine and metabolic function. The mechanisms of sleep-hormonal interactions, and therefore the endocrinometabolic consequences of age-related sleep alterations, which markedly differ from one hormone to another, are reviewed in this article.

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.

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 μnol/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 μg/l, a value not different from that observed in normal controls (262±16 μg/l). IGF-I levels were not modified by dialysis. In contrast, GH values were significantly higher in uremic patients (3.6± 0.6 μg/l) than in normal controls (2.5±0.5 μg/l) and decreased significantly after the dialysis session (0.8±0.1 μg/). 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.

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.

Effects of a 3-week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24-h hormonal profiles in postmenopausal women: a pilot study.

Dehydroepiandrosterone (DHEA) administration is widely evocated as a ‘fountain of youth’, but previous studies have provided inconsistent results. We aimed to investigate in healthy postmenopausal women the effects of a 3‐week oral DHEA administration on individual steroid levels, multiple 24‐h hormonal profiles and sleep architecture.