ContextIn young adults, sleep affects the regulation of growth hormone (GH)
and cortisol The relationship between decreased sleep quality in older adults
and age-related changes in the regulation of GH and cortisol is unknownObjectiveTo determine the chronology of age-related changes in sleep duration
and quality (sleep stages) in healthy men and whether concomitant alterations
occur in GH and cortisol levelsDesign and SettingData combined from a series of studies conducted between 1985 and 1999
at 4 laboratoriesSubjectsA total of 149 healthy men, aged 16 to 83 years, with a mean (SD) body
mass index of 241 (23) kg/m2, without sleep complaints or histories
of endocrine, psychiatric, or sleep disordersMain Outcome MeasuresTwenty-four–hour profiles of plasma GH and cortisol levels and
polygraphic sleep recordingsResultsThe mean (SEM) percentage of deep slow wave sleep decreased from 189%
(13%) during early adulthood (age 16-25 years) to 34% (10%) during midlife
(age 36-50 years) and was replaced by lighter sleep (stages 1 and 2) without
significant increases in sleep fragmentation or decreases in rapid eye movement
(REM) sleep The transition from midlife to late life (age 71-83 years) involved
no further significant decrease in slow wave sleep but an increase in time
awake of 28 minutes per decade at the expense of decreases in both light non-REM
sleep (−24 minutes per decade; P<001) and
REM sleep (−10 minutes per decade; P<001)
The decline in slow wave sleep from early adulthood to midlife was paralleled
by a major decline in GH secretion (−372 µg per decade; P<001) From midlife to late life, GH secretion further
declined at a slower rate (−43 µg per decade; P<02) Independently of age, the amount of GH secretion was significantly
associated with slow wave sleep (P<001) Increasing
age was associated with an elevation of evening cortisol levels (+193 nmol/L
per decade; P<001) that became significant only
after age 50 years, when sleep became more fragmented and REM sleep declined
A trend for an association between lower amounts of REM sleep and higher evening
cortisol concentrations independent of age was detected (P<10)ConclusionsIn men, age-related changes in slow wave sleep and REM sleep occur with
markedly different chronologies and are each associated with specific hormonal
alterations Future studies should evaluate whether strategies to enhance
sleep quality may have beneficial hormonal effects

https://jamanetwork.com/journals/jama/articlepdf/192981/JCI00039.pdf

Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men.

To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone.

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Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.

To evaluate the effects of obesity on the hypothalamo-pituitary-testicular axis, we compared total and free (FT) testosterone (T), androstenedione, dehydroepiandrosterone and its sulfate, and 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide, and estradiol levels in a group of 35 obese [body mass index (BMI), > 30] men (aged 17-61 yr) to levels in a nonobese control group. We observed a highly significant negative correlation (P < 0.001) between plasma (F)T levels and BMI and a significant positive correlation (P < 0.01) between E2 levels and BMI. There were no differences between the obese and the nonobese men in levels of androstenedione, dehydroepiandrosterone sulfate, and 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide. Insulin levels were significantly higher in obese men and were significantly (P < 0.02) correlated with the waist hip girth ratio. To evaluate the role of the hypothalamo-pituitary complex in the decreased (F)T levels in obese men, diurnal (0800-2000 h) LH pulsatility was studied in eight obese middle-aged men and eight age-matched controls. The pulsatility of plasma cortisol levels was also studied. Whereas LH pulse frequency was similar in the obese and control subjects, mean diurnal LH levels, mean diurnal LH pulse amplitude, and the sum of all diurnal LH pulse amplitudes and secretory masses were significantly lower in the obese than in the controls. Moreover, there was a highly significant correlation between the sum of LH pulse amplitudes and plasma (F)T levels. This decrease in LH pulse amplitude is not an isolated phenomenon of hypothalamo-pituitary dysfunction in obese men, because the pulse amplitude of plasma cortisol levels was also decreased. The decreased LH pulse amplitude together with the normal respond of Leydig cells to hCG stimulation reported in the literature suggest by inference that the decreased FT levels in obese men are the consequence of a hypogonadotropism. The decreased LH pulse amplitude and the decreased amplitude of cortisol pulses, and hence probably of ACTH pulses, point toward a general alteration of hypothalamo-pituitary function in obese men.

Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men.

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.

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

In order to determine the mechanism by which glucocorticosteroids decrease the serum concentration of thyrotropin (TSH), we studied eight normal subjects before and after they received 16 mg of dexamethasone daily for 2½ days. Serum levels of TSH and prolactin (PRL) were measured in the basal state and in response to the intravenous administration of 200 μg thyrotropinreleasing hormone (TRH); T4, free T4 (fT4), T3, and free T3 (fT3) were measured before TRH injection. Metabolic clearance rates of TSH corrected for body surface area (MCR-TSH/m2) were determined by the method of constant infusion to equilibrium; the production rates of TSH (PR-TSH/m2) were calculated. Dexamethasone produced a decrease in basal TSH from 2.2 to 0.8 μU/ml (P < 0.02), a statistically insignificant elevation in MCR-TSH/m2 from 25.8 to 34.1 ml/min/m2, and a decrease in PRTSH/m2 from 79 to 30 mU/day/m2 (P < 0.01). Peak TSH response to TRH decreased from 16.4 to 5.8 μU/ml (P < 0.005), as did TSH reserve from 1.58 to 0.54 m...

The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin.

Hourly integrated concentrations (IC) of growth hormone (GH), prolactin (PRL) and cortisol were determined by a continuous sampling procedure in six obese women, before and at the end of a 12 day fast, and in eight normal controls under basal conditions. Hormonal 24 h IC and nyctohemeral variations were calculated from these data. Nyctohemeral rhythms were investigated by the periodogram method. A significant increase over basal values of 24 h IC of PRL, GH and cortisol was observed at the end of the fasting period. Nyctohemeral variations--but not nyctohemeral rhythm--of IC-GH were found in normal subjects. They were abolished in obese patients under basal conditions but restored during fasting. The circadian rhythm of cortisol was not altered in obesity. A shift of the normal nyctohemeral rhythm of PRL was observed in obese patients, but the normal pattern was restored during fasting.

Simultaneous study of cortisol, growth hormone and prolactin nyctohemeral variations in normal and obese subjects. Influence of prolonged fasting in obesity

Radioimmunoassay of human growth hormone using a charcoal-dextran separation procedure.

Prolactin release after injection of thyrotrophin-releasing hormone in man.

The 24-hour profile of plasma levels of immunoreactive beta-MSH (IR-beta MSH), ACTH and cortisol was obtained at 15-min intervals in six normal males in summer and winter In the radioimmunoassay used, dilution curves of human beta-MSH and human beta-LPH were not parallel A seasonal variation in basal pituitary-adrenal secretion, with higher levels in winter than in summer, was demonstrated A circadian rhythm was found to be significant for ACTH, IR-beta MSH and cortisol in all investigations Whereas ACTH and cortisol patterns were largely concordant in all studies, there was a significant desynchronization of the circadian rhythm of IR-beta MSH as compared to ACTH in five cases Eighty-three percent of the secretory spikes of cortisol but only 68% of the IR-beta MSH spikes were concomitant with an ACTH spike Correlations between maximal levels of concomitant spikes were higher during the quiescent period of pituitary-adrenal secretion (2200--0400) for ACTH-cortisol whereas for ACTH-IR-beta MSH, highest correlations were found during the active early morning secretory phase (0400--1000) For the three plasma constituents studied, longer apparent half-lives were found to occur when the basal level before spiking was already elevated, suggesting that ACTH, beta-LPH and cortisol are secreted in bursts superimposed on a continuous basal secretion Absolute increments of concentration appeared to be relatively independent of the level before spiking It is suggested that the dissociations between ACTH and IR-beta MSH fluctuations in plasma observed here result from in vitro proteolysis of beta-LPH

Seasonal, circadian and episodic variations of human immunoreactive β-MSH, ACTH and cortisol

The effects of 200 microgram thyrotrophin-releasing hormone (TRH) i.v. on thyrotrophin (TSH), prolactin (PRL), growth hormone (GH) and triiodothyronine (T3) were studied in eight patients with barbiturate coma due to attempted suicide, in the same patients after recovery, in eight depressive patients and in eight normal controls. The patients with barbiturate coma presented normal basal TSH and PRL, elevated basal GH and normal PRL but blunted TSH responses to TRH; their GH concentrations varied widely without consistent relation to TRH administration. The same patients after recovery from coma presented normal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a clear-cut rise in GH (i.e. more than 10 ng/ml) occurred after TRH administration. The depressive patients presented normal basal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a moderated rise in GH (less than 10 ng/ml) occurred after TRH administration. The increment in T3 concentrations 120 min after TRH was found reduced in the comatose patients only. Basal cortisol was measured in all the subjects and found elevated in the comatose patients only. It is concluded that the abnormal TSH and GH responses to TRH observed in patients with barbiturate coma are more likely related to depressive illness than to an effect of barbiturates at the pituitary level. Barbiturates might affect thyroid secretion.

R. Leclercq

Papers

Simultaneous study of cortisol, growth hormone and prolactin nyctohemeral variations in normal and obese subjects. Influence of prolonged fasting in obesity

Radioimmunoassay of human growth hormone using a charcoal-dextran separation procedure.

Prolactin release after injection of thyrotrophin-releasing hormone in man.

Seasonal, circadian and episodic variations of human immunoreactive β-MSH, ACTH and cortisol

Thyrotrophin, prolactin and growth hormone responses to TRH in barbiturate coma and in depression.