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Biomedical subjects

A D Rogol

Publications and source records attributed to A D Rogol.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of leptin during childhood growth and development.

Leptin, the product of the ob/ob gene in rodents, regulates energy balance and fertility. Two genetic models, the ob/ob mouse (deletion of leptin protein) and the db/db mouse (deletion of leptin receptor) have markedly augmented research in obesity. Human obesity is more closely linked to leptin resistance than to the absence of leptin. Serum leptin concentrations reflect the size of the subcutaneous fat depot better than total fat mass or abdominal visceral fat. At the initiation of puberty there is a divergence in circulating leptin concentrations between boys and girls. In boys, leptin concentrations increase and then markedly decrease to prepubertal concentration levels. In girls there are only increasing concentrations. The authors believe these patterns are relevant to the markedly different alterations in the regional distribution of body fat that occurs in boys and girls at puberty.

Adipose Tissue↗
PubMed1999

Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth.

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.

Adolescent↗
PubMed1998

Androgen replacement in children with constitutional delay of puberty: the case for aggressive therapy.

Puberty describes the complex physiological transition between childhood and adulthood. Dramatic physical changes occur, most notably the development of secondary sexual characteristics and the pubertal growth spurt. During the adolescent growth spurt, growth velocity increases from pre-pubertal rates of 4-6 cm per year to as much as 10-15 cm per year. Accompanying the increase in gonadal steroids is an increase in amplitude of growth hormone secretory bursts. Evidence suggests that adequate growth hormone and gonadal steroids are both necessary for the attainment of a normal pubertal growth velocity, and the complex interplay between these two hormonal axes is under intense investigation. Delayed onset of puberty, or constitutional delay of growth and adolescence, is a common phenomenon presenting particularly in boys. Physiologically, it represents an extension of the normal pre-pubertal hypogonadotropic hypogonadal state. Without intervention, these children will spontaneously undergo puberty and often reach their genetic height potential, but their delay compared with that of their peers is often of concern to the children and their families. Recent evidence suggest long-term physiological benefits of early androgen replacement therapy in these boys, including maximizing attained bone mineral density. Androgen replacement therapy in male adolescents with constitutional delay of growth and adolescence is beneficial psychologically as well as physiologically and should be initiated promptly.

Adolescent↗
PubMed1998

Repeated bouts of exercise alter the blood lactate-RPE relation.

PURPOSE: To examine the effects of repeated bouts of exercise on the blood lactate [HLa]-ratings of perceived exertion (RPE) relation. METHODS: Six moderately trained males were studied on two occasions: a sequential exercise bouts day (SEB: 1000 h, 1130 h, and 1300 h) and a delayed exercise bouts day (DEB: 1000 h, 1400 h, and 1800 h). Each of the three exercise bouts within a given condition were 30 min in duration at the power output (PO) associated with 70% of VO2peak on a cycle ergometer. A standardized meal was provided at 0600 h. VO2, PO, HR, and RER were recorded every min during exercise and blood [HLa] and RPE were measured every 5 min during exercise. RESULTS: A 2 x 3 analysis of variance with repeated measures revealed that blood [HLa] decreased significantly with each repeated exercise bout (X +/- SEM: bout 1: SEB = 3.5 (0.3), DEB = 3.8 (0.4); bout 2: SEB = 2.6 (0.3), DEB = 2.8 (0.3); bout 3: SEB = 2.0 (0.2), DEB = 2.1 (0.4); mM). No differences were observed in the blood [HLa] response to repeated bouts of exercise between SEB and DEB. RPE-peripheral (legs, RPE-L) was higher during bout 3 compared with bout 1 (P <0.05) (bout 1: SEB = 11.8 (0.8), DEB = 12.3 (0.2); bout 2: SEB = 12.3 (0.5), DEB = 13.3 (0.4); bout 3: SEB = 13.5 (0.8), DEB = 14.0 (0.7); RPE-central (chest and breathing, RPE-C) was not affected by repeated bouts of exercise, whereas RPE-Overall (RPE-O) was higher during bout 3 compared with bouts 1 and 2 (P < 0.05) (bout 1: SEB = 12.5 (0.2), DEB = 12.3 (0.4); bout 2: SEB = 12.8 (0.4), DEB = 12.7 (0.4); bout 3: SEB = 13.7 (0.7), DEB = 13.2 (0.3)). No interaction for RPE x condition was observed. HR increased with repeated bouts of exercise with HR during exercise bout 3 being higher than HR during exercise bout 1 (164 vs. 156 bpm, P < 0.05). There was also a strong trend for HR during exercise bout 3 to be higher than HR during exercise bout 2 (P < 0.06). A trend for a reduction in VO2 with repeated exercise was observed (P < 0.07), with the reduction apparently related to the SEB condition (P < 0.12 for VO2 x condition). PO and kcal.min-1 were not affected by repeated bouts of exercise. RER decreased significantly with each repeated bout of exercise (from RER = 0.96 to RER = 0.89, P < 0.05) with no difference observed between SEB and DEB. CONCLUSIONS: We conclude that the blood [HLa]-RPE relation is altered by repeated bouts of exercise and that this alteration does not appear to be affected by recovery time between exercise bouts (up to 3.5 h of recovery). These data suggest that, after the first exercise bout, RPE should not be used to produce a specific blood [HLa] on subsequent exercise bouts.

Adult↗
PubMed1998

Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids.

Little is known about the influence of adiposity and hormone release on leptin levels in children and adolescents. We utilized criterion methods to examine the relationships among sex steroids, body composition (4 compartment), abdominal visceral and subcutaneous fat (magnetic resonance imagery), total subcutaneous fat (sum of 9 skinfolds), energy expenditure (doubly labeled water), aerobic fitness, and serum leptin levels in prepubertal and pubertal boys (n = 16; n = 13) and girls (n = 12; n = 15). The sum of skinfolds accounted for more variance in leptin levels of all girls [coefficient of determination (R2) = 0.70, P < 0.001] and all boys (R2 = 0.60, P < 0.001) than the total fat mass (girls, R2 = 0.52, P < 0.001; boys, R2 = 0.23, P < 0.001). Total energy expenditure, corrected for the influence of fat-free mass, correlated inversely with leptin (R2 = 0.18, P = 0.02). Gender differences in leptin disappeared when corrected for sex steroid levels or the combination of adiposity and energy expenditure. In multiple regression, the sum of skinfolds and free testosterone and estrogen levels accounted for 74% of the variance in leptin levels. We conclude that serum leptin levels are positively related to subcutaneous adiposity but negatively related to androgen levels. Energy expenditure may be negatively related to leptin levels by reduction of the adiposity, or a common genetic factor may influence both the activity and serum leptin levels.

Abdomen↗
PubMed1998

Discordant puberty in monozygotic twin sisters with neurofibromatosis type 1 (NF1).

Monozygotic twin sisters are reported who have discordant pubertal growth and sexual development. Although both sisters were physiologically appropriate for chronological age in their pubertal development, their adolescent development was considerably different from that expected of monozygotic twin sisters. The more pubertally advanced sister by magnetic resonance imaging had an optic pathway glioma while none was present in her twin sister. Precocious puberty is not an unexpected complication of neurofibromatosis type 1 and is always associated with the presence of an optic pathway glioma. These sisters emphasize the striking similarity that is expected of monozygotic twins and the need for investigation when intertwin differences in growth and/or development arise.

Birth Weight↗
PubMed1998

Alterations in growth and body composition during puberty: III. Influence of maturation, gender, body composition, fat distribution, aerobic fitness, and energy expenditure on nocturnal growth hormone release.

We examined the relationships among gender, sexual maturation, four-compartment model estimates of body composition, body fat distribution (magnetic resonance imaging for abdominal visceral fat and anthropometrics), aerobic fitness, basal and total energy expenditure, and overnight GH release in an ultrasensitive chemiluminescence assay in healthy prepubertal and pubertal boys (n = 18 and 11, respectively) and girls (n = 12 and 18, respectively). Blood samples were withdrawn every 10 min from 1800-0600 h to determine the area under the serum GH-time curve (AUC), sum of the GH peak heights (sigma GH peak heights), and the mean nadir GH concentration. GH release was greater in the pubertal than prepubertal subjects due to an increase in sigma GH peak heights (43.8 +/- 3.6 vs. 24.1 +/- 3.5 ng.mL-1, P = 0.0002) and mean nadir (1.7 +/- 0.2 vs. 0.7 +/- 0.2 ng.mL-1, P = 0.0002), but not peak number (4.3 +/- 0.2 vs. 4.5 +/- 0.2). The girls had a greater sigma GH peak heights (39.0 +/- 3.5 vs. 28.8 +/- 3.6 ng.mL-1, P = 0.05) and mean nadir concentration (1.4 +/- 0.2 vs. 0.9 +/- 0.2 ng.mL-1, P = 0.05) than the boys. Significant inverse relationships existed between sigma GH peak heights (r = -0.35, P = 0.06) or mean nadir (r = -0.39, P = 0.04) and four-compartment percent body fat for all boys but not for all girls or when combining all subjects. For all girls, significant inverse relationships existed between sigma GH peak heights (r = -0.39, P = 0.03) or mean nadir (r = -0.37, P = 0.04) and waist/hip ratio. Similar inverse relationships in all boys or all subjects were not significant. Forward stepwise regression analysis determined that bone age (i.e. maturation, primary factor) and gender were the significant predictors of AUC, sigma GH peak heights, and mean nadir. The influence of maturation reflects rising sex steroid concentrations, and the gender differences appear to be because of differences in estradiol concentrations rather than to body composition or body fat distribution.

Adipose Tissue↗
PubMed1998

The effects of pubertal status and glycemic control on the growth hormone-IGF-I axis in boys with insulin-dependent diabetes mellitus.

Dysregulation of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in children and adolescents with insulin-dependent diabetes mellitus (IDDM) is well documented. Elevated levels of circulating GH, increased GH secretory amplitude, and decreased concentrations of IGF-I, IGFBP-3, and GHBP have been related to poor glycemic control. We proposed that pubertal maturation may be a more significant factor, potentially overriding the effects of metabolic control, especially during mid-puberty when the GH-IGF-I axis is maximally stimulated. We studied 24 male children and adolescents with IDDM over a 5 year period. Subjects were grouped both by pubertal stage (prepubertal vs mid-pubertal) and by level of glycemic control (hemoglobin A1 (<9%, 9-11.5%, and >11.5%). Twenty-four hour every 20 minute blood sampling for GH determination was analyzed using the Cluster algorithm, and static measures of IGF-I, IGFBP-3, and GHBP were obtained. When analyzed by pubertal status, we found no difference in the number of GH secretory peaks or the interval between concentration peaks. The sum of the peak heights and area under the curve were significantly greater in the mid-pubertal boys, as was the average GH nadir. Serum levels of IGF-I and IGFBP-3 were greater in the mid-pubertal boys, but levels of GHBP were higher in the prepubertal boys. When analyzed by level of glycemic control, we found no differences in the number of GH secretory peaks or interval between peaks among the 3 groups. However, the sum of the peak heights, area under the curve, and average GH nadir were all lower in the group with the intermediate level of glycemic control (HgbA1 9-11.5%); no differences were observed between the other 2 groups. This relationship persisted when the mid-pubertal subjects were analyzed separately. No differences were found among the 3 groups for levels of IGF-I, IGFBP-3, or GHBP. We conclude that normal increases in GH secretion and levels of IGF-I and IGFBP-3 occur during mid-puberty in boys with IDDM. A concomitant increase in average GH nadir may reflect an underlying effect of metabolic control. Greater GH secretion was observed in the groups with the lowest and highest levels of glycemic control. We speculate that this may be related to an increased incidence of severe hypoglycemic episodes in the group with the lowest levels of glycosylated hemoglobin, resulting in metabolic derangements similar to those with elevated glycosylated hemoglobin levels.

Blood Glucose↗
PubMed1997

Exercise and growth hormone: does one affect the other?

The release of growth hormone (GH) is sensitive to many pharmacologic and physiologic stimuli, including exercise. Although the role of the increased amount of GH released during exercise is not fully understood, it most likely contributes to metabolic fuel adaptations during exercise, and tissue repair after the exercise session. The GH response to exercise is altered by many factors, including sex steroid concentrations, fitness level, and the intensity of previous exercise sessions. For both endurance and resistance exercise, greater activation of anaerobic glycolysis and lactate formation increases the amount of GH released. Whether an endurance exercise session or an endurance exercise training regimen influences the total amount of GH released during a 24-hour period is not clear; this may depend on the gender of the person, the intensity of the exercise, and the duration of exercise training. The influence of a single session of resistance exercise or resistance training on 24-hour GH secretion has not been studied. Preexercise diet modulation (especially modulation of fat intake) may also influence the release of GH during endurance exercise. Studies that measure the 12- to 24-hour GH response to resistance exercise after the ingestion of various macronutrient diets have not been completed.

Adaptation, Physiological↗
PubMed1997

Serum lipid levels and steroidal hormones in women runners with irregular menses.

This study compared the lipid profile of women runners with menstrual cycle irregularities with their normally menstruating counterparts. Relationships among selected steroid hormones and serum lipid levels in 10 eumenorrheic (EU) and 8 oligo-/amenorrheic (O/A) women runners and 6 eumenorrheic controls (CON) were examined. Serum 17 beta-estradiol (E2), progesterone (Prog), and dehydroepiandrosterone-sulfate (DHEAS) concentrations were determined in daily blood samples for 21 days, and integrated concentrations were calculated. Fasting blood samples were analyzed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL2, HDL3, triglycerides (Trig), and apolipoproteins A-1, A-II, and B. The O/A group had significantly lower E2 and Prog than EU or CON groups. Women in the CON group had lower HDL-C and HDL3 than the runners. With all women grouped together, E2 was not significantly correlated with any measured blood lipid parameters. On the other hand, DHEAS was significantly correlated with HDL-C, HDL2, and apolipoprotein A-I. These data demonstrate that women runners, regardless of menstrual cycle status, exhibit higher HDL-C concentrations than CON and supports previous research reporting a positive association between DHEAS and HDL-C.

Adolescent↗
PubMed1997

Alterations in growth and body composition during puberty. I. Comparing multicompartment body composition models.

A four-compartment (4C) model of body composition was used as a criterion to determine the accuracy of three-compartment (3C) and two-compartment (2C) models to estimate percent body fat (%BF) in prepubertal and pubertal boys (genital I & II, n = 17; genital III & IV, n = 7) and girls (breast I & II, n = 8; breast III & IV, n = 15). The 3C water-density (3C-H2O) and 3C mineral-density models, dual-energy X-ray absorptiometry, the Lohman age-adjusted equations, the Slaughter et al. skinfold equations, and the Houtkooper et al. and Boileau bioelectrical impedance equations were evaluated. Agreement with the 4C model increased with the number of compartments (i.e., body water, bone mineral) measured. Except for the 3C-H2O model, the limits of agreement were large and did not perform well for individuals. The mean %BF by dual-energy X-ray absorptiometry (23.6%) was greater than that of the criterion 4C method (21.7%). For the field methods, the Slaughter et al. skinfold equations performed better than did the Houtkooper et al. and Boileau bioimpedance equations. The hydration of the fat-free mass decreased (genital I & II = 75.7%, genital III & IV = 74.8%, breast I & II = 75.5%, breast III & IV = 74.4%) and the mineral content increased (genital I & II = 4.9%, genital III & IV = 5.0%, breast I & II = 5.1%, breast III & IV = 5.7%) with maturation. The density of the fat-free mass also increased (genital I & II = 1.084 g/ml, genital III & IV = 1.087 g/ml, breast I & II = 1.086 g/ml, breast III & IV = 1.091 g/ml) with maturation. All of the models reduced the %BF overprediction of the Siri 2C model, but only the 4C and 3C-H2O models should be used as criterion methods for body composition validation in children and adolescents.

Adipose Tissue↗
PubMed1997

Human growth hormone response to repeated bouts of aerobic exercise.

We examined whether repeated bouts of exercise could override growth hormone (GH) auto-negative feedback. Seven moderately trained men were studied on three occasions: a control day (C), a sequential exercise day (SEB; at 1000, 1130, and 1300), and a delayed exercise day (DEB; at 1000, 1400, and 1800). The duration of each exercise bout was 30 min at 70% maximal O2 consumption (VO2max) on a cycle ergometer. Standard meals were provided at 0600 and 2200. GH was measured every 5-10 min for 24 h (0800-0800). Daytime (0800-2200) integrated GH concentrations were approximately 150-160% greater during SEB and DEB than during C: 1,282 +/- 345, 3,192 +/- 669, and 3,389 +/- 991 min.microgram.l-1 for C, SEB, and DEB, respectively [SEB > C (P < 0.06), DEB > C (P < 0.03)]. There were no differences in GH release during sleep (2300-0700). Deconvolution analysis revealed that the increase in 14-h integrated GH concentration on DEB was accounted for by an increase in the mass of GH secreted per pulse (per liter of distribution volume, lv): 7.0 +/- 2.9 and 15.9 +/- 2.6 micrograms/lv for C and DEB, respectively (P < 0.01). Comparison of 1.5-h integrated GH concentrations on the SEB and DEB days (30 min exercise + 60 min recovery) revealed that, with each subsequent exercise bout, GH release apparently increased progressively, with a slightly greater increase on the DEB day [SEB vs. DEB: 497 +/- 162 vs. 407 +/- 166 (bout 1), 566 +/- 152 vs. 854 +/- 184 (bout 2), and 633 +/- 149 vs. 1,030 +/- 352 min.microgram.l-1 (bout 3), P < 0.05]. We conclude that the GH response to acute aerobic exercise is augmented with repeated bouts of exercise.

Adult↗
PubMed1997

Food availability affects neural estrogen receptor immunoreactivity in prepubertal mice.

How underfeeding delays maturation of the central mechanisms affecting GnRH release at the onset of puberty, and why females are more sensitive to underfeeding than males are not well understood. We tested the hypothesis that the sexually dimorphic effects of underfeeding on GnRH release are mediated in part through the estrogen receptor (ER). We investigated the influence of underfeeding on the number of ER-immunoreactive (ER-ir) cells in the medial preoptic area (mPOA), ventromedial nucleus (VMN), and arcuate nucleus (ARH) of prepubertal CF-1 mice, neural areas known to influence GnRH release. In females, 7 days of underfeeding reduced detectable ER-ir cells in the mPOA and VMN, but not in the ARH. Also, we noted a direct relationship between the percent body weight change the last 24 h before perfusion and the numbers of ER-ir cells in the mPOA (r = 0.69; P = 0.0008) and VMN (r = 0.56; P = 0.01). In males, 17 days of underfeeding did not affect ER-ir cell numbers in any region. A subsequent investigation of the time course of alterations in ER immunoreactivity revealed that in female mice ER-ir cell numbers were reduced within 48 h of underfeeding in the mPOA, VMN, and ARH. ER-ir cell number was not changed in male mice. When female mice were underfed for 48 h and then refed, ER-ir cell numbers normalized by 24 h in the mPOA, VMN, and ARH. For the time-course experiments, the percent body weight change the last 24 h before perfusion and the number of ER-ir cells were related in the mPOA (r = 0.47; P < 0.001) and VMN (r = 0.49; P < 0.001), but not in the the ARH (r = 0.23; P < 0.12) in female mice, and in the mPOA (r = 0.66; P < 0.001), VMN (r = 0.33; P = 0.06), and ARH (r = 0.45; P = 0.007) in male mice. Thus, despite no significant change in ER-ir cell number in the male mice, there was a relationship between the percent body weight change during the last 24 h before perfusion and the number of ER-ir cells. We conclude that in male mice, correlation analyses between the percent body weight change before perfusion and ER-ir cell number may be a more sensitive marker of the metabolic condition at the time of perfusion. In female mice, underfeeding may stall puberty by reducing the number of ER-ir cells in brain areas important for signal transmission of GnRH release.

Animal Feed↗
PubMed1997

Estrogen and testosterone, but not a nonaromatizable androgen, direct network integration of the hypothalamo-somatotrope (growth hormone)-insulin-like growth factor I axis in the human: evidence from pubertal pathophysiology and sex-steroid hormone replacement.

Activation of the gonadotropic and somatotropic axes in puberty is marked by striking amplification of pulsatile neurohormone secretion. In addition, each axis, as a whole, constitutes a regulated network whose feedback relationships are likely to manifest important changes at the time of puberty. Here, we use the regularity statistic, approximate entropy (ApEn), to assess feedback activity within the somatotropic (hypothalamo-pituitary/GH-insulin-like growth factor I) axis indirectly. To this end, we studied pubertal boys and prepubertal girls or boys with sex-steroid hormone deficiency treated short-term with estrogen, testosterone, or a nonaromatizable androgen in a total of 3 paradigms. First, our cross-sectional analysis of 53 boys at various stages of puberty or young adulthood revealed that mean ApEn, taken as a measure of feedback complexity, of 24-h serum GH concentration profiles is maximal in pre- and mid-late puberty, followed by a significant decline in postpubertal adolescence and young adulthood (P = 0.0008 by ANOVA). This indicates that marked disorderliness of the GH release process occurs in mid-late puberty at or near the time of peak growth velocity, with a return to maximal orderliness thereafter at reproductive maturity. Second, oral administration of ethinyl estradiol for 5 weeks to 7 prepubertal girls with Turner's syndrome also augmented ApEn significantly (P = 0.018), thus showing that estrogen per se can induce greater irregularity of GH secretion. Third, in 5 boys with constitutionally delayed puberty, im testosterone administration also significantly increased ApEn of 24-h GH time series (P = 0.0045). In counterpoint, 5 alpha-dihydrotestosterone, a nonaromatizable androgen, failed to produce a significant ApEn increase (P > 0.43). We conclude from these three distinct experimental contexts that aromatization of testosterone to estrogen in boys, or estrogen itself in girls, is likely the proximate sex-steroid stimulus amplifying secretory activity of the GH axis in puberty. In addition, based on inferences derived from mathematical models that mechanistically link increased disorderliness (higher ApEn) to network changes, we suggest that sex-steroid hormones in normal puberty modulate feedback within, and hence network function of, the hypothalamo-pituitary/GH-insulin-like growth factor I axis.

Adolescent↗
PubMed1997

The short-term infusion of ovine corticotropin-releasing hormone does not alter luteinizing hormone concentrations in young adult men.

Chronic stress leads to suppression of the hypothalamic-pituitary-gonadal (HPG) axis with decreased plasma LH concentrations. This is believed to be due to the influence of elevated levels of endogenous CRH mediated via the endogenous opiate peptide receptor. Efforts to reproduce this phenomenon with exogenous CRH have produced varied results depending on the dose and route of administration of CRH as well as on the species, gonadal state, and endogenous opiate peptide system tone of the experimental subjects. In humans, conflicting results for CRH-induced suppression of the HPG axis exist for women, and the issue has not been addressed sufficiently in men. We, therefore, studied the effects of a 4-h infusion of ovine CRH (oCRH) on LH secretion in 11 healthy, nonobese young adult men (age range, 20-33 yr). Subjects were admitted to the General Clinical Research Center on 4 occasions in randomized order. They underwent blood sampling for LH at 10-min intervals from 1800-0600 h. From 2200-0200 h, subjects received one of the following iv infusion protocols in blinded fashion: a normal saline (NS) bolus and NS infusion, a naloxone (NAL) bolus (4 mg) and NAL infusion (2 mg/h), a NS bolus and oCRH infusion (1 microgram/kg.h; maximum, 75 micrograms/h), and a NAL bolus and both NAL and oCRH infusions, using the above-mentioned doses. For each time point, serum LH values from the four experimental conditions were compared by one-way ANOVA with repeated measures; the paired t test was applied post-hoc. This experimental model is predicted to have a beta-error of less than 0.10 for identifying a 1.0 U/L change in LH levels. As expected, NAL was associated with a transient, but significant, rise in serum LH concentrations compared to those in the NS control. On the other hand, oCRH administration did not result in any significant alteration in either basal or NAL-stimulated LH levels. We conclude that exogenous oCRH administration does not significantly alter pituitary secretion of LH in healthy men. We speculate that any suppressive effect of CRH on the HPG axis occurs at the level of the hypothalamus.

Adult↗
PubMed1997

Maturation of the regulation of growth hormone secretion in young males with hypogonadotropic hypogonadism pharmacologically exposed to progressive increments in serum testosterone.

To study the onset of the action of gonadal sex steroids on the GH axis in spontaneous puberty, which is prolonged and sparingly predictable, we present a clinical investigative paradigm in which six previously untreated boys with isolated hypogonadotropic hypogonadism were exposed to progressively higher testosterone levels designed to mimic the androgen environment recognized during the early stages of puberty. We administered three incremental doses of testosterone (25-, 50-, and 100-mg im injections), each over a period of 4 weeks. Studies of overnight pulsatile GH secretion and GH responses to GHRH alone or combined with L-arginine (a functional somatostatin antagonist) were performed before testosterone administration and after each dose of testosterone. Serum testosterone, but not estrogen, levels increased progressively in all subjects during therapy. Deconvolution analysis of GH release profiles disclosed that GH secretory burst mass was stimulated significantly even by 25 mg testosterone. This parameter was not altered further by higher doses of testosterone. Spontaneous GH secretory burst number and amplitude increased significantly only after the 50- and 100-mg testosterone treatments, after which the serum GH response to GHRH and arginine also rose significantly. In contrast, the GH response to GHRH alone was not significantly affected by any dose of testosterone. Serum testosterone levels correlated significantly with the primary parameters of nocturnal GH secretion. In summary, our experimental model suggests that in males even very small increases in circulating testosterone occurring during the earliest stages of puberty are able to amplify pulsatile GH secretion. Our concomitant secretagogue data further suggest that testosterone exerts its action at different sites in the hypothalamo-somatotropic axis, i.e. directly at the pituitary level, and also at hypothalamic loci, possibly increasing both GHRH and somatostatin release.

Adolescent↗