Elevated rectal temperature produced by all-night bright light is reversed by melatonin infusion in men.

Early morning rectal body temperature is lowest when melatonin levels are highest in humans. Although pharmacological doses of melatonin are hypothermic in humans, the relationship between endogenous melatonin and temperature level has not been investigated. We measured rectal body temperature in nine normal men whose melatonin levels were suppressed by all-night sleep deprivation in bright light and compared values with those seen in sleep in the dark, sleep deprivation in dim light (to control for the stimulatory effect of wakefulness on temperature), and sleep deprivation in bright light with an infusion of exogenous melatonin that replicated endogenous levels. Minimum rectal temperature, calculated from smoothed temperature data from 2300 to 0515 h, was greater in bright-light sleep deprivation, resulting in suppression of melatonin, than in conditions of sleep deprivation in dim light or sleep in the dark. An exogenous melatonin infusion in bright light returned the minimum temperature to that seen in dim-light sleep deprivation. A nonsignificant elevation in mean and minimum temperature was noted in all conditions of sleep deprivation relative to sleep. We conclude that melatonin secretion contributes to the lowering of core body temperature seen in the early morning in humans.

Sleep deprivation reduces LH secretion in men independently of melatonin.

Melatonin affects gonadal function in non-primate mammals. Confirmatory data in man are not available. We assessed melatonin's acute effects on luteinizing hormone secretion in 17 normal men. We studied these men in conditions of sleep in the dark, and sleep deprivation in bright light, dim light, and bright light combined with a physiologically relevant infusion of melatonin, while measuring blood levels of immunoreactive LH every 20 min for 7 h. We compared overnight LH secretion, and LH pulse frequency, amplitude, length, interval and area under the curve using a modification of the PULSAR peak identification program, among the four treatments. Areas under the curve for peaks in all three conditions of sleep deprivation were lower than in normal sleep. The presence or absence of melatonin had no additional effect. We conclude that acute suppression of melatonin does not affect LH pulse parameters in normal man, but that sleep deprivation may reduce the amount of LH secreted per pulse.

Supplemental growth hormone alters body composition, muscle protein metabolism and serum lipids in fit adults: characterization of dose-dependent and response-recovery effects.

Using double-blind, placebo-controlled procedures, the effects of low and high therapeutic dosages of methionyl-human growth hormone (met-hGH) on body composition, muscle protein metabolism and serum lipids were studied in 7 fit adults without growth hormone (GH) deficiency. Dose-dependent changes in body composition were observed that in part appeared to be influenced by a response-recovery effect, as measured by responses factored according to the duration of washout between exposure to the low and high dosages of met-hGH (6 weeks vs. 12 weeks vs. 18 weeks). Increases in fat-free weight were accompanied by an increase in skeletal muscle protein metabolism. Basal levels of cholesterol were inversely related to peak levels of GH in response to exercise stimulation and IGF-I, while GH supplementation lowered levels of total cholesterol and high- and low-density lipoproteins. A dose-dependent effect occurred for total cholesterol, and the percent change in cholesterol was related to the percent change in insulin-like growth factor I (IGF-I). Endogenous levels of GH were attenuated in response to stimulation and IGF-I levels were increased after treatment with GH, but no dose-dependent changes were observed. We conclude that met-hGH alters body composition and muscle protein metabolism, and decreases stored and circulating lipids in fit adults with a pre-existing supranormal body composition. The physiological profile of the person was not as important as the treatment conditions in determining the somatic and physiological response outcomes.

Increase in plasma melatonin, beta-endorphin, and cortisol after a 28.5-mile mountain race: relationship to performance and lack of effect of naltrexone.

Strenuous exercise increases plasma melatonin, cortisol, and beta-endorphin concentrations. Furthermore, a relationship between endogenous opioids and melatonin has been proposed. We measured plasma melatonin, cortisol, and beta-endorphin in 46 subjects before and after a 28.5-mile high altitude race. Thirteen of the subjects received the orally active opioid antagonist naltrexone immediately before the race. The mean plasma melatonin, cortisol, and beta-endorphin levels were higher after the race than before it; the melatonin results were confirmed by gas chromatography-mass spectrometry assay of 12 subjects. Naltrexone had no effect on the increase in any of the three hormones. The run-induced increases in plasma melatonin, beta-endorphin, and cortisol were negatively correlated with finishing time, but only the plasma beta-endorphin and cortisol rises correlated with each other. We conclude that prolonged exercise in trained athletes can increase plasma melatonin and that this rise is not due to the concomitant opioid release.

Questionnaire assessment of lifetime and recent exposure to environmental tobacco smoke.

In a sample of 149 adult nonsmokers recruited in New Mexico in 1986, the authors assessed the reliability of questionnaire responses on lifetime exposure to tobacco smoke in the home. They also compared urinary cotinine levels with questionnaire reports of environmental tobacco smoke exposure during the previous 24 hours. The agreement of responses obtained on two occasions within six months was high for parental smoking during childhood: 94% for the mother and 93% for the father. For the amounts smoked by the mother and the father during the subject's childhood, the agreement between the two interviews was moderate: 52% and 39%, respectively. For the number of hours per day that each parent smoked in the home during the subject's childhood, the Spearman correlation coefficients also indicated only moderate reliability (r = 0.18 for maternal smoking and r = 0.54 for paternal smoking). For each set of interviews, responses concerning recent tobacco smoke exposure and urinary cotinine levels were correlated to only a modest degree. The authors conclude that adults can reliably report whether household members smoked during their childhood, but information on quantitative aspects of smoking is reported less reliably.

Augmented pituitary corticotropin response to a threshold dosage of human corticotropin-releasing hormone in depressives pretreated with metyrapone.

We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.

Lack of an acute modulatory effect of melatonin on human nocturnal thyrotropin and cortisol secretion.

Using a recently developed model for investigating the neuroendocrine role of melatonin in man, we studied melatonin's effect on the nocturnal secretion of thyrotropin and cortisol in 17 normal male volunteers. The model consists of sleep in the dark and all-night sleep deprivation in conditions of: bright light with and without a melatonin infusion, and dim light. We have improved our infusion paradigm so that levels of melatonin during infusion are now indistinguishable from those occurring during sleep in the dark or dim light sleep deprivation. Sleep deprivation per se raised TSH levels compared to normal sleep. However, the three conditions of sleep deprivation could not be distinguished from each other, which suggests that the suppression of TSH by sleep (or the stimulation of TSH by sleep deprivation) is not mediated by melatonin. Cortisol secretion was unaffected by sleep deprivation regardless of melatonin's presence or absence. However, a difference in the pattern of secretion of cortisol in the sleep condition in the early morning (compared to the sleep deprivation conditions) was noted. These data do not implicate melatonin in the acute regulation of TSH or cortisol in normal man. These data also provide a method of melatonin infusion that replicates the pattern and levels seen in sleep.

Body composition response to exogenous GH during training in highly conditioned adults.

The effects of biosynthetic methionyl-human growth hormone (met-hGH) on body composition and endogenous secretion of growth hormone (GH) and insulin-like growth factor I (IGF-I) were studied in eight well-trained exercising adults between 22 and 33 yr of age. By the use of double-blind procedures, met-hGH (2.67 mg/0.5 ml diluent, 3 days/wk) and bacteriostatic water (placebo, 0.5 ml, 3 days/wk) were administered in a repeated-measures design that counterbalanced treatment order. Duration of each treatment was 6 wk. Subjects trained with progressive resistance exercise throughout and were maintained on a high-protein diet monitored by extensive compositional analyses of daily dietary intake records. Hydrodensitometry revealed that met-hGH significantly decreased percent body fat (%fat) and increased fat-free weight (FFW) and FFW/fat weight (FW), whereas the placebo treatment did not change any of these measures. Changes in FFW/FW correlated with the relative dose of met-hGH but did not correlate with either the peak GH response to L-dopa/arginine stimulation or IGF-I levels obtained after treatment with placebo. There were no differences between treatments in the dietary intakes of total kilocalories, protein, carbohydrates, and fat. Mean IGF-I levels were elevated after treatment with met-hGH compared with postplacebo levels. After treatment with met-hGH, five of seven subjects had a suppressed GH response to stimulation from either L-dopa/arginine or submaximal exercise. We conclude that supraphysiological doses of met-hGH will alter body composition in exercising adults in a relative dose-dependent manner and that such treatment may suppress endogenous release of GH in some individuals.

Discrepancies between self-reported and validated cigarette smoking in a community survey of New Mexico Hispanics.

In a population-based survey of respiratory disease in New Mexico Hispanics, we validated self-reports of cigarette use by 1,317 subjects against salivary cotinine level and end-tidal carbon monoxide concentration. For identifying likely deceivers about cigarette smoking among self-reported never smokers and former smokers, we used cutoff values of 20 ng/ml and 8 parts per million (ppm) for salivary cotinine and carbon monoxide, respectively. Among males and females, age-standardized prevalences of current smokers based upon questionnaire reports were 30.9 and 27.1%, respectively. After adjustment for cotinine alone, these percentages were 36.2 for males and 31.1 for females, and after adjustment for cotinine and carbon monoxide level, the corresponding percentages were 39.1 for males and 33.2 for females. We conclude that self-reports about smoking habits may lead to underestimation of the prevalence of current smokers and that questionnaire responses should be validated with biologic markers of tobacco smoke exposure.

Prolactin, cortisol, and antidepressant treatment.

In four depressed patients with abnormal dexamethasone suppression test results before treatment, plasma prolactin levels significantly increased after successful amitriptyline therapy. Such an increase did not take place in five depressed patients with normal dexamethasone suppression test findings.

Effects of bromocriptine on sweat gland function during heat acclimatization.

This study examined the involvement of the hormones aldosterone and prolactin in sweat gland function during heat acclimatization. Two groups of male subjects (n = 8) were tested - one receiving a placebo (control), the other receiving bromocriptine. Both groups performed cycle ergometer exercise at 50% of maximal oxygen uptake over 10 consecutive days in an environmental chamber maintained at 39 degrees C and 30% relative humidity. Duration of exercise was 90 min on days 2-4 and 6-9, and 45 min on test days 1, 5 and 10. Electrolyte concentrations were determined by total body washdown. Prolactin increased (p less than 0.001) during exercise on day 1 in the control group but not on days 5 and 10. In contrast, prolactin was suppressed by bromocriptine and did not rise in response to exercise or heat exposure. Plasma aldosterone increased during exercise in both groups, showing no differences between groups. The sodium concentration in sweat decreased significantly (p less than 0.05) in the control group from day 1 to 10 but was unchanged in the treatment group. These data suggest that acclimatization-related changes in sweat gland function may be attenuated by increases in central dopaminergic activity and implicate prolactin in control of sweat gland function.

Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion.

In order to assess the potential relationship between human growth hormone (GH) and body composition (BC) and natural immunity (NI), we measured the effects of exogenous GH on fat weight (FW), fat-free weight (FFW), and the cytotoxic activity of natural killer (NK) cells in women with impaired GH secretion. Mean peak serum concentrations of GH in response to L-dopa/arginine stimulation were 6.2 +/- 1.1 (SEM) ng/mL in 6 untreated subjects (US) and 5.4 +/- 1.5 ng/mL in 6 GH-treated subjects (TS). Moreover, the pretreatment circulating levels of IGF-I were low in both groups (US 684 +/- 121 mU/mL and TS 583 +/- 83 mU/mL), and they correlated with pretest levels of NK cell activity (r = .59, P less than .05) when both groups were combined. The TS were given 700 micrograms of human GH IM for an average of 14 days while the US were studied in parallel without GH treatment. As measured by hydrodensitometry or skinfold anthropometry, FW decreased (26.1 +/- 6.8 kg to 23.8 +/- 6.3 kg, P less than .05) and FFW increased (44.9 +/- 3.3 kg to 46.2 +/- 3.8 kg, P less than .05) in the TS. In the US, there were no significant (P less than .05) changes in either FW or FFW. Using a standard 51Cr release assay to measure the specific lytic (SL) activity of NK cells, mean SL activity increased from 24.4 +/- 7.0% to 44.1 +/- 8.9% (P less than .05) in the TS, whereas levels in the US were not altered significantly (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperhydration with glycerol solutions.

Glycerol was tested as an agent to promote hyperhydration of male and female subjects. Series I experiments involved ingesting 0.5, 1.0, or 1.5 g glycerol/kg body wt and within 40 min drinking 0.1% NaCl, 21.4 ml/kg. In series II, 1.0 g glycerol/kg body wt was ingested at time 0, and 25.7 ml/kg of 0.1% NaCl was ingested over a 3.5-h period. Experiments were of 4-h duration and included controls without glycerol as each subject served as his/her control. Blood samples were taken at 40- or 60-min intervals for hemoglobin (Hb), hematocrit (Hct), plasma osmolality, glycerol, and multiple blood chemistry analyses. Urine was collected at 60-min intervals. Glycerol ingestion increased plasma osmolality for 2 h and reduced the total 4-h urine volume. There were no significant changes in Hb or Hct as a result of the glycerol or excess fluid intake. This study demonstrates that glycerol plus excess fluid intake can produce hyperhydration for at least 4 h.

A model for the study of the acute effects of melatonin in man.

The role of the pineal hormone melatonin in human physiology is uncertain. Previous studies correlated plasma melatonin levels with several physiological parameters or determined the responses to pharmacological doses of melatonin during daylight hours. We established an acute model that is more rigorously physiological. Constant nocturnal bright light in sleep-deprived normal men resulted in low plasma melatonin levels throughout the night, in contrast to sleep in the dark and dim light sleep deprivation nights. Subsequently, melatonin was infused during bright light exposure to approximate physiological levels. Plasma GH and PRL measurements in these four conditions revealed an effect of sleep deprivation independent of the presence or absence of melatonin. A subsample of these men had an intermediate level of melatonin suppression with 500 lux light intensity, relative to those during sleep and bright light. The results suggest that melatonin has no acute modulatory effect on the secretion of these two sleep-related hormones.

Salivary cotinine levels and involuntary tobacco smoke exposure in children and adults in New Mexico.

We conducted a population-based household survey of respiratory disease in 2,029 children and adults and measured salivary cotinine levels by radioimmunoassay in 1,360 nonsmokers and ex-smokers. At all ages median and mean cotinine levels among nonsmokers and ex-smokers increased with the number of smokers in the home. The prevalence of a detectable level of cotinine was about 35% for those not living with a cigarette smoker and was greater with the number of cigarettes smoked by household members. In a multiple logistic regression model, the major determinants of a detectable level of cotinine in children were mother's smoking (odds ratio (OR) = 3.2), father's smoking (OR = 2.1), and smoking of other household members (OR = 4.0). Among adults, the effects of spouse's smoking were smaller with OR = 1.3 and 1.4 for husband's and wife's smoking, respectively. We conclude that in the general population cotinine can be frequently detected in the saliva of nonsmokers, even among those not living with a smoker.

Site of inhibitory action of CRE 9-41 on ACTH release from isolated rat pituitary cells.

The corticotropin-releasing factor (CRF) analog CRF 9-41 inhibits CRF, but not forskolin or dibutyryl cyclic AMP, stimulated release of ACTH from isolated pituitary cells. CRF 9-41 also blocks CRF-stimulated accumulation of cyclic AMP in a parallel dose dependent fashion. CRF 9-41 has no effect on basal ACTH release or cAMP levels. This substantiates that the analog acts as a direct CRF antagonist and that the site of this inhibition is most likely at the level of binding of CRF to its receptor on the corticotrope. Various substances, including most prominently glucocorticoids, inhibit release of ACTH from the pituitary. In an effort to develop another class of inhibitors, Rivier et al recently synthesized analogs of corticotropin releasing factor (CRF). One among these, alpha-helical ovine CRF 9-41 blunts adrenalectomy and stress induced ACTH release in non-anesthetized rats. At micromolar concentrations, CRF 9-41, shifts rightward the dose response of isolated pituitary cells to ovine CRF. Thus, the authors suggested that CRF 9-41 acts as a competitive antagonist to CRF-induced ACTH secretion. CRF appears to act through stimulation of adenylate cyclase. To determine the potential site of action of CRF 9-41 in the activation sequence for adenylate cyclase, we studied its effects on pituitary cyclic AMP formation and ACTH secretion from dispersed anterior pituitary cells derived from normal adult rats, as well as, its interaction with cyclic nucleotide agonists.

Lipemic and lipoproteinemic effects of natural and synthetic androgens in humans.

Testosterone cypionate administration in weight-trained subjects reduced serum high-density lipoprotein cholesterol (HDL-C) levels without affecting the total cholesterol (Total-C)/HDL-C ratio. Nandrolone decanoate administration also reduced HDL-C levels, but elevated the Total-C/HDL-C ratio. These findings could not be attributed to changes in exercise patterns, dietary intake, or alcohol consumption. It is concluded that the synthetic androgen employed in this study produced a worsening of potential lipid-related risk factors for ischemic heart disease and that exogenous testosterone has a much less pronounced effect on such risk factors.

Prolactin responses to chronic exercise in males.

Chronic, as well as acute, exercise increases circulating PRL in females. The response of males to repeated exercise, however, is unknown. The purpose of the present study was to examine the effects of acute and chronic exercise on plasma PRL levels in untrained males. Eight male subjects performed cycle ergometer exercise at 50% of their maximal oxygen uptake on 10 consecutive days. The subjects exercised in an environmental chamber maintained at 39 degrees C and 30% relative humidity. PRL levels were measured on days 1, 5, and 10 before exercise, and after 20 and 45 minutes of exercise. Acute exercise increased PRL levels. However, plasma levels did not significantly increase during exercise on days 5 and 10. This suggests a similarity in the PRL response to acute exercise in males and females, but a sex difference in the response to chronic exercise.

Regulation by calmodulin of adenylate cyclase activity in anterior pituitary.

The control of adenylate cyclase activity is exerted through separate components: receptors, guanyl nucleotide-binding protein, catalytic subunit, calmodulin (CaM), and divalent cations. We examined the roles of CaM, Mg+2, and Ca+2 in the regulation of adenylate cyclase activity in plasma membranes from anterior pituitary. Adenylate cyclase activity was reduced with 2.5 mM EGTA, 125 micrograms/ml compound 48/80, and 200 microM trifluoperazine, which are known inhibitors of CaM in a variety of tissues. Mg+2, in excess of ATP, stimulated adenylate cyclase activity. Ca+2 produced a biphasic effect on adenylate cyclase activity over the concentration range of 0.1-10 mM, exhibiting inhibition up to 2.0 mM and stimulation above that. GTP, 5'-guanylylimidodiphosphate, and F- each enhanced adenylate cyclase activity, but activity stimulated after each of these agents was reduced or returned toward control values by administration of compound 48/80 or trifluoperazine. In the absence of free Mg+2 (i.e. Mg+2 in excess of ATP concentrations), 10 mM Ca+2 produced marked stimulation of adenylate activity which was not reduced by trifluoperazine. We concluded that the plasma membranes from anterior pituitary possess a CaM-dependent adenylate cyclase and that activation of adenylate cyclase by guanyl nucleotide-binding protein requires CaM. Ca+2 may have allosteric binding sites on the catalytic subunit, and Ca+2 and Mg+2 appear to have antagonistic effects at different binding sites.

Pituitary-testicular axis dysfunction in burned men.

Plasma total testosterone, free testosterone, LH, and sex hormone-binding globulin (testosterone-estradiol-binding globulin) were measured in adult men hospitalized for treatment of burns. Total testosterone was below the normal range in 37 of 41 patients. Free and total testosterone levels declined very rapidly after the burn, remained low for weeks, and rose toward the end of hospitalization, but usually had not reached normal levels at discharge. The more severe the burns, the lower were the testosterone levels. LH levels were below normal during the first 4 days after the burn and remained in the low or mid normal range thereafter. Sex hormone-binding globulin levels were normal or slightly low. The data suggest the presence of a central defect in the release of LH. Large doses of opiate analgesics or an increase in endogenous opiate peptides related to severe persistent pain might be contributing factors to the pituitary-testicular hypofunction found in burned men.