Integrated Concentration Of Growth Hormone Research Articles

Biomarqueurs en endocrinologie

TSH assay is the best parameter of the thyroid function. For adults, the normal interval of TSH concentrations range from 0.4 to 4 mUI/L. At the first trimester of pregnancy, TSH levels must be <2.5 mUI/L. Normal TSH levels increase with aging and obesity. The biological diagnosis relies on the identification of excessive secretion of the metanephrines which are more sensitive and specific than those of catecholamines. The concentrations of the free plasmatic metanephrines reflect the ongoing production of tumor. Plasma methoxytyramine is a novel biomarker of metastatic pheochromocytomas and paragangliomas. Serum IGF1 is a reliable measure of integrated GH concentrations in patients with acromegaly. Accurate assessment of IGF1 concentrations requires age and sex-matched control values. IGF1 is a sensitive tool for the diagnosis of acromegaly and efficacy of therapies. Serum AMH assay is more sensitive, more specific and more reproducible that counting of ovarian follicles by ultrasound. AMH level above 5 ng/mL (35 pmol/L) could be chosen as one of the diagnostic criteria for the polycystic ovary syndrome. In early or "incipiens" ovarian failure, the decrease in serum AMH is far ahead of the increase in FSH. Thyroglobulin (TG) and calcitonin (CT) are the sensitive and specific markers of respectively well-differentiated thyroid cancers of follicular origin and of the medullary thyroid cancers. The same tumour marker assay should be used to monitor a given patient. Chromogranin A (CgA) is a highly efficient biomarker for diagnosis and follow-up of various endocrine tumours. Despite the lack of international standardisation, some CgA assays are reliable.

Effects of Continuous Versus Intermittent Exercise, Obesity, and Gender on Growth Hormone Secretion

Obesity attenuates spontaneous GH secretion and the GH response to exercise. Obese individuals often have low fitness levels, limiting their ability to complete a typical 30-min bout of continuous exercise. An alternative regimen in obese subjects may be shorter bouts of exercise interspersed throughout the day. The objective of the study was to examine whether intermittent and continuous exercise interventions evoke similar patterns of 24-h GH secretion and whether responses are attenuated in obese subjects or affected by gender. This was a repeated-measures design in which each subject served as their own control. This study was conducted at the University of Virginia General Clinical Research Center. Subjects were healthy nonobese (n = 15) and obese (n = 14) young adults. Subjects were studied over 24 h at the General Clinical Research Center on three occasions: control, one 30-min bout of exercise, and three 10-min bouts of exercise. Twenty-four hour GH secretion was measured. Compared with unstimulated 24-h GH secretion, both intermittent and continuous exercise, at constant exercise intensity, resulted in severalfold elevation of 24-h integrated serum GH concentrations in young adults. Basal and pulsatile modes of GH secretion were attenuated both at rest and during exercise in obese subjects. The present data suggest that continuous and intermittent exercise training should be comparably effective in increasing 24-h GH secretion.

Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men

Circulating testosterone (T) and GH/IGF-I are diminished in healthy aging men. Short-term administration of high doses of T augments GH secretion in older men. However, effects of long-term, low-dose T supplementation on GH secretion are unknown. Our objective was to evaluate effects of long-term, low-dose T administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I and IGFBP-3 in healthy older men (65-88 yr, n = 34) with low-normal T and IGF-I. In a double-masked, placebo-controlled, randomized study we assessed effects of low-dose T supplementation (100 mg im every 2 wk) for 26 wk on nocturnal GH secretory dynamics [8 PM to 8 AM, Q(20) min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% (P = 0.004) and E(2) by 31% (P = 0.009) and decreased SHBG by 17% (P = 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% (P = 0.02) and pulsatile GH secretion by 79% (P = 0.05), primarily due to a twofold increase in GH secretory burst mass (P = 0.02) and a 1.9-fold increase in basal GH secretion rate (P = 0.05) vs. placebo. There were no significant changes in GH burst frequency or orderliness of GH release (ApEn). IGF-I levels increased by 22% (P = 0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We conclude that low-dose T supplementation for 26 wk increases spontaneous nocturnal GH secretion and morning serum IGF-I concentrations in healthy older men.

The impact of sex and exercise duration on growth hormone secretion

Previous research clearly indicates a linear relationship between exercise intensity and growth hormone (GH) release and that this relationship is influenced by sex. The present study examined the GH response to increasing exercise duration in young men and women. Fifteen healthy subjects (8 men and 7 women) completed three randomly assigned exercise sessions (30, 60, and 120 min) at 70% of peak oxygen consumption. Blood samples were collected every 10 min beginning 30 min before exercise, for a total of 240 min. Total integrated GH concentration (IGHC) increased with increasing exercise duration for men and women (601, 1,394, and 2,360 microg/l.4 h; 659, 1,009 and 1,243 microg/l.4 h for 30, 60, and 120 min of exercise, respectively). Regression analysis revealed that IGHC (logarithmically transformed) was significantly influenced by exercise duration (logarithmically transformed) (120 min > 60 min > 30 min) and that a significant sex-dependent effect was present even after adjustments for fitness level and percent body fat (men > women). The slope of the regression line was greater for men than for women (1.003 vs. 0.612; P = 0.013), but the average height of the regression line was greater for women (7.287 vs. 6.595; P < 0.001). Although GH secretory pulse half-duration was greater in women (P = 0.001), and GH half-life was greater in men (P = 0.001), they were not affected by exercise duration. The total mass of GH secreted during exercise increased with exercise duration (P < 0.001) but was not affected by sex (P = 0.137). Results from the present investigation indicate that when exercise intensity is constant, exercise duration significantly increases IGHC and that this relationship is sex dependent.

Nocturnal growth hormone secretory dynamics are altered after resistance exercise: deconvolution analysis of 12-hour immunofunctional and immunoreactive isoforms

To characterize the effects of daytime exercise on subsequent overnight growth hormone (GH) secretion and elimination dynamics, serum was sampled, and GH was measured every 10 min for 12 h (1800 to 0600) in a control (CON) condition and after a 50-set resistance exercise protocol (EX) from 1500 to 1700. GH was measured with a conventional immunoreactive (IR) and an immunofunctional (IF) assay, and values were analyzed via a multi-parameter deconvolution analysis. EX resulted in a higher overnight secretory burst frequency [CON: 7.6 (SD 2.4) < EX: 9.4 (2.2) bursts per 12 h, P = 0.005] but lower mean burst mass [CON: 9.2 (4.7) > EX: 6.0 (2.9) microg/l, P = 0.019] and secretory rate [CON: 0.68 (0.29) > EX: 0.48 (0.23) microg/l/min; P = 0.015; ANOVA main effect means presented]. Approximate entropy (ApEn) was greater after EX, indicating a less orderly GH release process than CON. The estimated half-life of IF GH was significantly lower than IR GH [IF: 15.3 (1.1) < IR 19.8 (1.6) min, P < 0.001] but similar between the CON and EX conditions (approximately 17 min). Despite the changes in secretory dynamics, 12-h mean and integrated GH concentrations were similar between conditions. The results suggest that although quantitatively similar total amounts of GH are secreted overnight in CON and EX conditions, resistance exercise alters the dynamics of secretion by attenuating burst mass and amplitude yet increasing burst frequency.

Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves

Perturbations in endocrine functions can impact normal growth. Endocrine traits were studied in three dwarf calves exhibiting retarded but proportionate growth and four phenotypically normal half-siblings, sired by the same bull, and four unrelated control calves. Plasma 3,5,3′-triiodothyronine and thyroxine concentrations in dwarfs and half-siblings were in the physiological range and responded normally to injected thyroid-releasing hormone. Plasma glucagon concentrations were different (dwarfs, controls > half-siblings; P < 0.05). Plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations in the three groups during an 8-h period were similar, but integrated GH concentrations (areas under concentration curves) were different (dwarfs > controls, P < 0.02; half-siblings > controls, P = 0.08). Responses of GH to xylazine and to a GH-releasing-factor analogue were similar in dwarfs and half-siblings. Relative gene expression of IGF-1, IGF-2, GH receptor (GHR), insulin receptor, IGF-1 type-1 and -2 receptors (IGF-1R, IGF-2R), and IGF binding proteins were measured in liver and anconeus muscle. GHR mRNA levels were different in liver (dwarfs < controls, P < 0.002; dwarfs < half-siblings, P = 0.06; half-siblings < controls, P = 0.08) but not in muscle. IGF-1R mRNA abundance in liver in half-siblings and controls was 2.4- and 2.5-fold higher ( P = 0.003 and P = 0.001, respectively) and in muscle tissue was 2.3- and 1.8-fold higher ( P = 0.01 and P = 0.08, respectively) than in dwarfs. Hepatic IGF-1R protein levels (Western blots) in muscle were 2.5-fold higher ( P < 0.05) and in liver and muscle (quantitative immunohistochemistry) were higher ( P < 0.02 and P < 0.07, respectively) in half-siblings than in dwarfs. The reduced presence of IGF-1R may have been the underlying cause of dwarfism in studied calves.

Growth hormone response to graded exercise intensities is attenuated and the gender difference abolished in older adults

We investigated the joint impact of age, gender, and exercise intensity on growth hormone (GH) secretion. At a university center, nine young men, eight young women, seven older men, and six older women were each tested on six randomly ordered occasions [control (C) and 5 exercise conditions (Ex)]. Serum GH concentrations were measured by immunochemiluminometry [10-min samples: 0700-0900 (baseline); 0900-1300 (C or Ex + recovery)]. Integrated GH concentrations (IGHC) were calculated by trapezoidal reconstruction, and GH secretion was modeled by deconvolution analyses. Subjects exercised from 0900 to 0930 at graded intensities [standardized to individual lactate threshold (LT)] of 25 and 75% of the difference between rest and LT, LT, and 25 and 75% of the difference between LT and peak oxygen consumption. Data were analyzed via mixed-effects ANOVA for repeated measures with post hoc contrasts. We found that 1) Ex elevated IGHC above C in all four cohorts, 2) 1.75 LT Ex resulted in maximal IGHC, 3) IGHC differed by gender in young (women > men) but not older adults, 4) older adults secreted 50% less GH during graded exercise, 5) Ex selectively augmented the mass of GH secreted per burst, and 6) higher Ex + recovery IGHC in young women was due to higher baseline IGHC, rather than greater stimulated GH secretion. We conclude that young women manifest a greater absolute and incremental IGHC response to exercise than postmenopausal women and men of any age. Age diminishes the GH response to exercise and abolishes the young-adult gender difference. Attenuation of GH responses to all exercise intensities in older adults has implications for exercise prescription because higher exercise intensities may be required to stimulate GH release in older adults.

Hormone-replacement therapy use, but not race, impacts the resting and exercise-induced GH response in postmenopausal women

This study examined the effect of hormone-replacement therapy (HRT) use on the incremental GH response to aerobic exercise in postmenopausal women and established whether racial differences in the GH response were seen at rest and in response to exercise. 13 white (n = 6, HRT; n = 7, no HRT) and seven black women (no HRT) were studied on two occasions, a control day and an exercise day (30 min at 70% VO(2)max on a cycle ergometer). Blood was sampled every 10 min for a 4-h period and analyzed for GH using an ultrasensitive chemiluminescent assay. The mean 4-h GH concentration was higher on both study days in the HRT women than the non-HRT users. The integrated GH concentrations were greater in the HRT women both at rest and in response to exercise (rest, 352 +/- 53 min microg l(-1); exercise, 711 +/- 57 min microg l(-1); P < 0.01) than in the non-HRT women (rest, 157 +/- 87 min microg l(-1); exercise, 248 +/- 94 min microg l(-1)). The incremental GH response was greater in the HRT users than in the non-HRT women (358 +/- 130 versus 90.8 +/- 94 min microg l(-1), respectively; P < 0.05). GH-production rate during the 4-h period was greater in the HRT women than in the non-HRT women (P < 0.01), due to an increase in the GH mass secreted/pulse (P < 0.05), with no change in GH pulse number or GH half-life. No racial differences in the mean 4-h GH concentrations or integrated GH concentrations were found at rest or in response to exercise. HRT use resulted in a greater incremental exercise response compared with non-HRT users, due to changes in the secretory pulse characteristics in the HRT users. This study also demonstrated that no racial differences exist at rest and in response to exercise in the morning hours.

Pubertal alterations in growth and body composition: IX. Altered spontaneous secretion and metabolic clearance of growth hormone in overweight youth

Deconvolution analysis was used to determine 12-hour spontaneous nocturnal growth hormone (GH) secretion and GH half-life in lean (body mass index, <85th percentile; n = 39) and overweight (body mass index, ≥85th percentile; n = 18) youth. The integrated GH concentration, GH burst mass, and half-life were lower ( P < .05) in overweight than in lean youth. For each unit increase in percentage of body fat, integrated serum GH concentrations, secretory burst mass, and half-life declined by 83.6 μg/L per minute ( r = −0.39, P < .01), 0.22 μg/L ( r = −0.28, P < .05), and 0.2 minute ( r = −0.38, P < .01), respectively. The effect of overweight on GH secretion was independent of pubertal status. Hierarchical regression models tested the hypothesis that altered GH secretion in youth is more related to total adiposity than abdominal visceral fat. When age, sex, fat-free mass, testosterone, and estradiol were held constant, the sequential addition of abdominal visceral fat did not increase R 2 for any GH secretion variable. Sequential addition of percentage of body fat increased R 2 ( P < .05) for integrated GH concentration, total secretory rate, secretory burst mass, and pulsatile production rate. We conclude that serum GH concentrations are reduced in overweight youth primarily because of reduced GH burst mass with no change in the number of secretory events and secondarily to reduced GH half-life. Based on the model that GH-releasing hormone predominantly increases GH pulse amplitude whereas somatostatin primarily controls GH pulse frequency, these results suggest that overweight in youth diminishes GH-releasing hormone stimulation resulting in truncated GH bursts but does not alter the number of somatostatin withdrawal intervals so that GH burst frequency is conserved.

Growth hormone responses to repeated bouts of aerobic exercise with different recovery intervals in cyclists

To characterise the specific GH responses to repeated bouts of standardised aerobic exercise in amateur competitive cyclists, 6 volunteers (mean age +/- SE: 28.7 +/- 2.3 yr, range: 18-35 yr) performed two consecutive 30-min cycling sessions at 80% of individual maximal oxygen uptake on three occasions with different time interval between bouts: 2 h (EXP A), 4 h (EXP B) and 6 h (EXP C). Serum GH concentration was determined in blood samples collected at 15-min intervals during exercise and following 1 h of recovery. In EXP A and EXP B, peak GH concentration in response to the second bout was significantly lower (p < 0.01) than that of the first bout, but in EXP C no difference was detected between bouts. Similarly, the average integrated GH concentration (AUC), determined during the exercise period and in the following 1 h of recovery in the course of the second bout, was significantly lower than that observed during the first bout only in EXP A (p < 0.05) and EXP B (p < 0.01) and not in EXP C, so that the second bout AUC of EXP C was significantly higher than that of EXP A (p < 0.01) and EXP B (p < 0.01). It was concluded that GH responses to subsequent bouts of aerobic exercise are dependent on the time interval between the exercise sessions.

Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation

ObjectiveTo study the influence of dietary intervention on plasma ghrelin levels in obese children and adolescents with anorexia nervosa (AN). Study designPrepubertal obese children (n=16) and 16 anorexic adolescents were studied at three different points: clinical diagnosis and after a reduction or recuperation of 25% and 50% of the initial BMI SD score. Controls included 21 Tanner growth stage 1 and 36 Tanner growth stage 5 subjects. We analyzed plasma ghrelin levels and their correlation with plasma levels of leptin, insulin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP-1), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and integrated concentration of growth hormone (ICGH) before and after dietary intervention. ResultsAt diagnosis, ghrelin levels were significantly decreased in obese children (52% of control levels) and significantly increased in adolescents with AN (164% of control levels). After dietary intervention, ghrelin increased in obese patients but without reaching control levels even after a 50% reduction in body mass index (BMI). In adolescents with AN, ghrelin levels normalized after a 25% increase in BMI. Ghrelin correlated negatively with the BMI and positively with IGFBP-1 levels in controls but not in obese patients or in patients with AN at diagnosis. The positive correlation between ghrelin and IGFBP-1 was recovered after dietary intervention. ConclusionsPlasma ghrelin levels present opposite changes in obesity and AN after dietary intervention, suggesting that ghrelin is a good marker of nutritional status.

Insulin-like growth factor-I: marker for diagnosis of acromegaly and monitoring the efficacy of treatment

Acromegaly is caused by chronic excess secretion of growth hormone (GH) and resultant persistent elevation in concentrations of insulin-like growth factor-I (IGF-I), also called somatomedin-C. A number of diagnostic tests are available to support the diagnosis of acromegaly, but those that rely on measurement of serum GH concentrations have important limitations. Concentrations of serum IGF-I, which is produced principally in the liver and mediates the actions of GH, have been shown to correlate with clinical and metabolic markers of disease activity. Additionally, normalisation of IGF-I levels in acromegaly is associated with the resolution of symptoms and normal life expectancy. Thus, serum IGF-I is an important marker of disease activity and a sensitive, practical, and reliable measure of integrated GH concentrations in patients with acromegaly.

Impact of abdominal visceral fat, growth hormone, fitness, and insulin on lipids and lipoproteins in older adults

We examined the relationship between abdominal visceral fat (AVF) and plasma concentrations of lipids and lipoproteins in 19 females (F) (not on estrogen) and 31 males (M) over the age of 60 (age = 66.8 years). In addition, the effects of growth hormone (GH) release, fitness (V̇o2 peak), insulin, and glucose concentrations (both fasting and in response to an oral glucose tolerance test) on lipids were examined. Subjects were categorized by low (L) and high (H) AVF (L < 130 cm2, H > 130 cm2), fat mass (FM) (above or below median value), and AVF corrected for fat mass. Factorial analysis of variance (ANOVA) showed that when subjects were divided by AVF and FM, similar results were observed with H > L (P <.05) for very–low-density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), VLDL-TG, apolipoprotein (apo)-B, apo-B VLDL, cholesterol (Chol)/high-density lipoprotein (HDL), LDL/HDL, apoB/A1 and L > H for HDL, HDL2, HDL3, apo A1, and LDL/apo-B LDL. Gender differences were also observed with F > M for Chol, LDL, HDL, and HDL2. When AVF was corrected for FM, these gender differences were still present. After correcting for FM, differences remained between H and L AVF groups for VLDL, TG, VLDL-TG, apo-B, apo-B LDL, apo-B VLDL, apoB/A1 (P <.05). Twenty-four hour integrated GH concentration (IGHC) was inversely related to VLDL, TG, VLDL TG, LDL TG, apoB, apoB VLDL, apoB LDL, Chol/HDL, LDL/HDL, and apoB/A1 in F, but not M (P <.05). V̇o2 peak was directly related to Chol, LDL, HDL3, and apoB LDL with stronger relationships observed in F. Fasting insulin was related to lipids and lipoproteins in both men and women. These data suggest that, in older adults, elevated levels of AVF, FM, and AVF corrected for FM are associated with unfavorable lipid-lipoprotein profiles and extend similar findings reported in younger males and females with elevated AVF. These data also support previous findings indicating that AVF is a primary determinant of GH release. Copyright 2003, Elsevier Science (USA). All rights reserved.

Amplified and orderly growth hormone secretion characterizes lean adolescents with polycystic ovary syndrome.

The present study evaluated the hypothesis that pulsatile GH secretion is altered in adolescents with polycystic ovary syndrome (PCOS). Thirteen adolescent girls with PCOS (ages 13-19 years) and ten eumenorrheic controls (ages 14-19 years) matched for a range of body mass index (BMI) values underwent blood sampling every 20 min for 12 h overnight. Serum concentrations of GH and LH were measured by specific immunofluorometric assays (IFMA). Pulsatile secretion was quantitated by deconvolution analysis and pattern orderliness by the approximate entropy (ApEn) statistic. Fasting serum androstenedione, testosterone, 17-hydroxyprogesterone, estrone, estradiol, insulin and IGF-I concentrations were measured by RIA, GH-binding protein (GHBP) by IFMA and IGF-binding protein (IGFBP)-1 and IGFBP-3 by IRMA. Twelve-hour mean and integrated GH concentrations, the mass of GH secreted per burst, and the GH pulse frequency were not distinguishable in patients with PCOS and controls as a whole. Subanalysis of non-obese (BMI<25 kg/m(2)) PCOS and healthy volunteers disclosed elevated 12-h GH production rates (P=0.03) and integrated serum GH concentrations (P=0.04) in (lean) patients with PCOS. ApEn analysis of the orderliness of GH release showed remarkably more regular GH secretion patterns (lower ApEn of GH release) in girls with PCOS compared with controls (P=0.02). Serum GHBP, IGF-I and IGFBP-3 concentrations were similar in both groups, whether lean or obese. However, IGFBP-1 levels were lower in the combined group of PCOS subjects compared with BMI-matched controls (P<0.05). In volunteers with PCOS, mean (12-h) serum GH concentrations correlated positively with mean serum LH levels (P=0.006). Based on deconvolution analysis, the 12-h production rate and the mass of GH secreted per burst also correlated strongly with the cognate LH measure (both predicted) (P=0.004) in PCOS. Androstenedione levels were also related to the 12-h GH secretion rate (P=0.02). This study shows that non-obese adolescents with PCOS secrete GH at a higher rate and with more orderly patterns, resembling a male profile. Determining whether this pattern reflects an intrinsic hypothalamic abnormality or is secondary to androgen excess in PCOS will require further studies.

Growth hormone release during acute and chronic aerobic and resistance exercise: recent findings.

Exercise is a potent physiological stimulus for growth hormone (GH) secretion, and both aerobic and resistance exercise result in significant, acute increases in GH secretion. Contrary to previous suggestions that exercise-induced GH release requires that a "threshold" intensity be attained, recent research from our laboratory has shown that regardless of age or gender, there is a linear relationship between the magnitude of the acute increase in GH release and exercise intensity. The magnitude of GH release is greater in young women than in young men and is reduced by 4-7-fold in older individuals compared with younger individuals. Following the increase in GH secretion associated with a bout of aerobic exercise, GH release transiently decreases. As a result, 24-hour integrated GH concentrations are not usually elevated by a single bout of exercise. However, repeated bouts of aerobic exercise within a 24-hour period result in increased 24-hour integrated GH concentrations. Because the GH response to acute resistance exercise is dependent on the work-rest interval and the load and frequency of the resistance exercise used, the ability to equate intensity across different resistance exercise protocols is desirable. This has proved to be a difficult task. Problems with maintaining patent intravenous catheters have resulted in a lack of studies investigating alterations in acute and 24-hour GH pulsatile secretion in response to resistance exercise. However, research using varied resistance protocols and sampling techniques has reported acute increases in GH release similar to those observed with aerobic exercise. In young women, chronic aerobic training at an intensity greater than the lactate threshold resulted in a 2-fold increase in 24-hour GH release. The time line of adaptation and the mechanism(s) by which this training effect occurs are still elusive. Unfortunately, there are few studies investigating the effects of chronic resistance training on 24-hour GH release. The decrease in GH secretion observed in individuals who are older or have obesity is associated with many deleterious health effects, although a cause and effect relationship has not been established. While exercise interventions may not restore GH secretion to levels observed in young, healthy individuals, exercise is a robust stimulus of GH secretion. The combination of exercise and administration of oral GH secretagogues may result in greater GH secretion than exercise alone in individuals who are older or have obesity. Whether such interventions would result in favourable clinical outcomes remains to be established.

Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men.

We studied 130 healthy aged women (n = 57) and men (n = 73), age 65-88 yr, with age-related reductions in insulin-like growth factor I and gonadal steroid levels to assess the interrelationships between cortisol and growth hormone (GH) secretion and whether these relationships differ by sex. Blood was sampled every 20 min from 8:00 PM to 8:00 AM; cortisol was measured by RIA and GH by immunoradiometric assay, followed by deconvolution analyses of hormone secretory parameters and assessment of approximate entropy (ApEn) and cross-ApEn. Cortisol mass/burst, cortisol production rate, and mean and integrated serum cortisol concentrations (P < 0.0005), and overnight basal GH secretion (P < 0.05), were elevated in women vs. men. Integrated cortisol concentrations were directly related to most measures of GH secretion in women (P < 0.01) and with mean and integrated GH concentrations in men (P < 0.05). Integrated GH concentrations were directly related to mean and integrated cortisol levels in women (P < 0.005) and men (P < 0.05), with no sex differences. There were no sex differences in cortisol or GH ApEn values; however, the cross-ApEn score was greater in women (P < 0.05), indicating reduced GH-cortisol pattern synchrony in aged women vs. men. There were no significant relationships of integrated cortisol secretion with GH ApEn, or vice versa, in either sex. Thus postmenopausal women appear to maintain elevated cortisol production in patterns that are relatively uncoupled from those of GH, whereas mean hormone outputs remain correlated.

Aging-related growth hormone (GH) decrease is a selective hypothalamic GH-releasing hormone pulse amplitude mediated phenomenon.

Aging is accompanied by declining growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels. The neuroendocrine mechanisms of this decline have been studied previously, but the interpretation of the data was confounded by the imprecision in GH measurements and by the intervening variables of altered body composition and decreased gonadal steroid milieu in the elderly subjects of both sexes. To study the contribution of aging per se, we evaluated discrete parameters of GH pulsatility in young (n = 8 women, n = 8 men) and elderly (n = 11 women, in 10 men) subjects closely matched for body mass index. Blood samples for GH were obtained every 10 minutes for 24 hours. Plasma GH was measured by a sensitive chemiluminescent assay. GH pulsatility was assessed using cluster analysis. The elderly subjects had plasma IGF-I levels and integrated GH concentrations that were 32% to -56% of their sex-matched younger counterparts. The age-associated attenuation in GH was due to a decrease in GH pulse amplitude, whereas pulse frequency and nadir levels were unchanged. The majority of the young subjects (81%) reached their peak GH during the "lights off" period, whereas the majority of the elderly subjects (62%) peaked during the "lights on" period (p = .01). We conclude that aging in both sexes is accompanied by profound decreases in GH output and in plasma IGF-I concentrations. This effect is separate from the alterations in body mass index that accompany the normal aging process. Attenuation of GH output associated with aging is related solely to the lower GH and, by inference, GH-releasing hormone (GHRH) pulse amplitude.

Growth hormone secretory dynamics over the menstrual cycle.

Whether GH secretion in women varies over the menstrual cycle is uncertain. Previous investigations have led to conflicting conclusions; some studies suggested that there is an estrogen mediated rise in GH during the periovulatory (PO) and luteal (L) phases whereas others indicated no change in GH axis over the cycle. Differences in conclusions could relate to heterogeneity of the study populations, GH sampling paradigms or sensitivity of the GH assays used. In order to investigate whether GH secretion varied over the cycle, 24-h GH profiles using every 10-min sampling were obtained in 6 ovulatory women during the early follicular (EF), PO and L phases of the cycle. The TSH response to TRH, GH response to GRH and fasting plasma IGF-I were measured on each occasion. There was a trend toward higher integrated GH concentration (IGHC) during the PO phase, although this difference was not statistically significant (3284+/-721 vs 4542+/-872 vs 4071+/-699 microg/min/L; EF vs PO vs L; p=0.09). Similarly, deconvolution estimated GH secretion did not vary over the cycle (p=0.56). There were no differences in GH pulse amplitude or frequency. There were no correlations between IGHC and sex steroids. Serum IGF-I was constant over the cycle (272+/-38 vs 277+/-31 vs 265+/-38 microg/L; p=0.89). The TSH response to TRH and GH response to GRH did not vary over the cycle. We concluded that the effect of changes in the ovarian steroid milieu on the GH axis during spontaneous menstrual cycles is minimal.

Obesity attenuates the growth hormone response to exercise.

Resting serum GH concentrations are decreased in obesity. In nonobese (NonOb) individuals, acute exercise of sufficient intensity increases GH levels; however, conflicting data exist concerning the GH response to exercise in obese individuals. To examine the exercise-induced GH response in obese individuals, we studied 8 NonOb, 11 lower body obese (LBO), and 12 upper body obese (UBO) women before, during, and after 30 min (0800-0830 h) of treadmill exercise at 70% oxygen consumption peak. Blood samples were taken every 5 min (0700-1300 h) and were analyzed for GH concentrations with a sensitive (0.002 microg/L) chemiluminescence assay. The impact of 16 weeks of aerobic exercise training on the GH response to exercise was also examined in the obese women. In response to exercise, the 6-h integrated GH concentration was significantly greater (P < 0.05) in the NonOb women (1006 +/- 220 min/microg x L) than in either of the obese groups (LBO, 435 +/- 136; UBO, 189 +/- 26 min/microg x L). No differences were found between the LBO and UBO women. The increased integrated GH concentrations could be accounted for by a greater 6-h GH production rate [micrograms per L distribution volume (Lv)] in the NonOb women than in either of the obese groups (NonOb, 45.6 +/- 12.3; LBO, 16.9 +/- 1.2; UBO, 8.7 +/- 0.64 microg/Lv; P < 0.05). This increase was attributed to a greater mass of GH secreted per pulse in the NonOb women (NonOb, 10.8 +/- 2.5; LBO, 4.9 +/- 0.8; UBO, 4.0 +/- 0.5 microg/Lv; P < 0.05, NonOb vs. both obese groups). After 16 weeks of aerobic training, maximal oxygen consumption increased from 44.7 +/- 2.2 to 48.5 +/- 1.9 mL/kg fat-free mass x min; P < 0.05), but no significant change in body composition occurred in the 10 obese women who completed the training. No change was observed in the GH response to exercise after training (n = 10; pre, 379 +/- 144; post, 350 +/- 55 min/microg x L). In conclusion, the GH response to exercise was attenuated in the obese women compared to NonOb women. Short term aerobic training improved fitness, but did not increase the GH response to exercise.

Cafeteria diet-induced obesity is associated with a low spontaneous growth hormone secretion and normal plasma insulin-like growth factor-I concentrations

Pituitary growth hormone (GH) secretion has been shown to be blunted in human and animal obesity. With respect to human obesity, cafeteria diet-induced obesity might be an appropriate model to study spontaneous GH secretion. In 6 cafeteria diet-overfed obese male Wistar rats and 6 control rats with chronically implanted catheters, GH levels were measured every 15 min over 6 h by standard RIA. A significantly lower GH secretion, reflected by the integrated GH concentration, was found in the obese rats (median 16.46, [range 10.55-19.13] ng/ml x 6 h vs 35.63 [range 21.90-41.50] ng/ml x 6 h, P < 0.05). The GH secretion in the obese rats was significantly negatively correlated with the body fat percentage, assessed by dual X-ray absorptiometry (Rho = -0.95, P < 0.05). Median plasma insulin-like growth factor-I (IGF-I) concentration was comparable between the two groups, while the median insulin concentration was significantly higher in the obese group (1.95 [range 1.76-3.55] ng/ml vs 1.21 [range 0.86-2.13] ng/ml, P < 0.05). No significant correlation existed between GH secretion and the plasma insulin concentration. In conclusion, cafeteria diet-induced obesity is associated with a low spontaneous GH secretion and normal plasma IGF-I concentration. The hyperinsulinemia present in this model probably explains the normal IGF-I concentrations, but not the GH hyposecretion.