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Biomedical subjects

A D Rogol

Publications and source records attributed to A D Rogol.

At least 91 records · Page 5Linked to original sources
PubMed1992

Elevated growth hormone secretory rate in premature infants: deconvolution analysis of pulsatile growth hormone secretion in the neonate.

Premature infants have higher circulating concentrations of growth hormone (GH) than term infants. Previous investigations of these differences have used sampling frequencies of every 30 min with subsequent application of pulse detection algorithms, such as the CLUSTER program, to assess serum GH pulse parameters. To determine differences in GH secretory rates or GH t1/2 values between premature and term infants, we have sampled 11 neonates at 15-min intervals. We performed deconvolution analysis of the resultant plasma GH values to estimate GH secretory and clearance parameters. Five premature infants (gestational age range 24-34 wk) and six term infants (gestational age range 38-42 wk) were sampled every 15 min for 6 h. All subjects had indwelling arterial catheters. GH was measured (in duplicate) by RIA using 10 microL of plasma. Premature infants had higher secretory burst amplitudes (2.2 +/- 0.13 micrograms/L/min versus 1.4 +/- 0.27 micrograms/L/min, p = 0.02), higher production rates (product of the total number of bursts and the mean mass of GH secreted per burst, 811 +/- 173 micrograms/L/6 h versus 283 +/- 77 micrograms/L/6 h, p = 0.03), and a higher mass of GH per secretory burst (106 +/- 25 micrograms/L versus 38 +/- 11 micrograms/L, p = 0.049) than term infants. The integrated plasma GH concentration exhibited a strong trend toward a higher value in the premature infants (18,100 +/- 800 micrograms/L versus 10,200 +/- 2,700 micrograms/L, p = 0.067).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1992

Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: relationship to age, pubertal status, and body mass.

Mean plasma GH concentrations increase in normal boys during mid- to late-puberty. To investigate the nature of the pituitary secretory events and/or altered metabolic clearance responsible for these serum GH concentration changes, we performed multiple-parameter deconvolution analysis of 46 24-h serum GH concentration-time series obtained from normal boys at various stages of puberty and young adulthood. The subjects ranged in chronological age from 7-27 yr. The height and weight of each subject were between the 5th and 95th percentile for age. The calculated daily mass of GH secreted was greatest (P less than 0.001) in late pubertal boys (mean +/- SE, 1810 +/- 250 micrograms/24 h) and was triple the value in prepubertal boys (610 +/- 65 micrograms/24 h). When the values were normalized and expressed as mass of GH secreted per unit (m2) body surface area or per L distribution volume, GH secretion in late pubertal boys was still significantly greater than that in any other group (P less than 0.05). These values for late pubertal boys were nearly double the corresponding values for prepubertal boys (1160 +/- 160 vs. 600 +/- 58 micrograms GH/m2.24 h and 440 +/- 63 vs. 270 +/- 25 micrograms GH/L vol.24 h, respectively). When the effect of clearance mechanics on serum GH concentrations was removed mathematically, the primary change in predicted GH secretory burst parameters during pubertal development was an increase in GH mass released per burst resulting from an increase in the maximal rate of GH secretion attained within the bursts. These changes in the amplitude of GH release events were specific, in that they were largely independent of any accompanying alterations in duration or frequency of the GH secretory bursts or in serum GH half-life. Correlation analysis revealed that the 24-h GH secretion rate varied inversely with the subjects' body mass index SD score (r = -0.65; P less than 0.01), suggesting that differences in body mass, even within the normal range, contribute to the wide variability in daily GH secretion rates among normally growing children. The plasma insulin-like growth factor-I concentrations of all subjects correlated positively with the calculated 24-h GH secretion rate (r = 0.51; P less than 0.001). In summary, the primary neuroendocrine alteration responsible for the augmented serum GH concentrations characterizing mid- to late-puberty in boys is an increased mass of GH released per pituitary secretory episode resulting from an increased maximal rate of GH secretion within each burst.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Properties of spontaneous growth hormone secretory bursts and half-life of endogenous growth hormone in boys with idiopathic short stature. Genentech Collaborative Group.

We analyzed endogenous GH secretory dynamics and MCRs by a novel quantitative deconvolution technique in 20 boys with idiopathic short stature (ISS) and 35 boys of normal stature in Tanner stage I of puberty. We tested the null hypotheses that 1) ISS is not associated with any alterations in the frequency, mass, amplitude, or duration of spontaneous GH secretory bursts and/or the 24-h GH production rate; and 2) the half-life of endogenous GH is not altered in ISS. The boys with ISS had a mean (+/- SEM) bone age of 8.0 +/- 0.42 yr and a chronological age of 10 +/- 0.50 yr. The latter was similar to the chronological (and bone) age of the normal boys of 9.8 +/- 0.23 (and 9.3 +/- 0.34) yr. Mean height SD scores were significantly lower in ISS boys, viz. -2.7 +/- 0.15 in ISS vs. +0.34 +/- 0.13 in normal boys (P less than 0.001). Plasma insulin-like growth factor-I concentrations were similar in the two groups, as were (24-h) mean serum GH concentrations, viz. 3.5 +/- 0.29 micrograms/L in ISS and 4.1 +/- 0.49 micrograms/L in normal boys (P = NS). Deconvolution analysis revealed that the mean number of GH secretory events per 24 h was similar in normal and ISS boys, viz. 9.6 +/- 0.76 (normal) vs. 8.4 +/- 0.55 (ISS), and that there was no significant difference in mean GH interburst intervals. The amplitude, mass, and duration of computer-resolved GH secretory bursts also did not differ in normal and ISS boys. The half-lives of endogenous GH were estimated to be 16 +/- 0.77 min in the ISS and 18 +/- 0.93 min in the control boys (P = NS). The calculated daily GH secretion rate per unit distribution volume was not significantly reduced in ISS, i.e. 194 +/- 19 micrograms/L.day in ISS vs. 177 +/- 19 micrograms/L.day in control boys. Moreover, daily GH secretion rates corrected for body mass index (weight/height2) in the twp groups were not significantly different. In summary, the present cohort of boys with ISS manifested no significant alterations in GH secretory burst frequency, duration, mass, or amplitude or in the half-life of endogenous GH compared to normal boys in Tanner stage I of pubertal development. Indeed, whether daily GH secretion rates are expressed per unit distribution volume or per unit body mass index, groups of boys with ISS and normal height controls secrete similar total amounts of GH. We conclude that the overall dynamics of GH secretion and clearance in boys with ISS considered as a whole cannot be distinguished readily from physiological patterns observed in prepubertal boys of normal height.

Adolescent↗
PubMed1992

Anabolic-androgenic steroids and the adolescent.

This article has reviewed some of the hormonal and behavioral maturation that occurs during adolescence, which are characterized by remarkable physical changes and behavioral vulnerability. Risk taking of many varieties is common and drugs (including anabolic-androgenic steroids) form a part of the prevailing culture in many places. These steroids probably are not severe health hazards when taken intermittently and in low to moderate doses. The 17-alkylated derivatives are clearly the more likely to cause hepatotoxicity. Thus, the scare tactics formerly used (severe constitutional side effects) are doomed to failure. The tenuous link between these drugs and objective behavioral and addictive effects must be strengthened before health strategies based on this issue can be validated. Clearly, the lack of scientific information has impeded, if not precluded, the formulation of an effective health education strategy. The most potent deterrent to the use of steroid drugs by athletes must be the moral issue of fair play and maintaining a "level playing field." We strongly support directed research in these areas and hope that the credibility of the scientific community can be regained after its faulted "stop steroid use" campaigns based on the lack of steroid efficacy in bringing about desired results or on their dire consequences have been replaced with credible evidence to refute their use on these and other grounds.

Adolescent↗
PubMed1992

Long-term endurance training alters the hypothalamic-pituitary axes for gonadotropins and growth hormone.

In a prospective fashion we have studied the impact of chronic exercise of two intensities on the hypothalamic-pituitary-end organ axes for gonadotropins and GH in gynecologically mature, previously sedentary women. Physiologic alterations are evident in both axes with a doubling of 24-hour mean serum GH concentrations at 1 year and smaller, transient changes in pulsatile LH release during the first four menstrual cycles. The latter period of physiologic adaptation should be studied more intensively with more frequent exercise evaluation. Perhaps more significant "adaptation to stress" would be quantitated. We also emphasize that gynecologically less mature women were not studied and only the early follicular phase was evaluated. Adaptive changes of greater magnitude (including amenorrhea) might have been produced if a different group of women, a markedly different training regimen, or a different phase of the menstrual cycle were studied. Finally, whether or not they participate in physical training, younger amenorrheic women are at increased risk for diminished lumbar spine bone mineral content and skeletal fractures.

Exercise↗
PubMed1991

Function of the growth hormone-insulin-like growth factor I axis in the profoundly growth-retarded diabetic child: evidence for defective target organ responsiveness in the Mauriac syndrome.

Mauriac syndrome (MS) consists of a triad of poorly controlled diabetes, profound growth retardation, and hepatomegaly. The mechanisms involved in the growth retardation of those patients are not well understood. In an attempt to determine whether the growth retardation was secondary to somatroph secretory failure, abnormal pulsatile secretion, deletion of the growth hormone (GH) receptor, inadequate insulin-like growth factor I (IGF-I) generation, or abnormal IGF-I binding proteins (IGFBPs) two patients with MS were studied and their results compared with those of age-matched diabetic boys of similar glycemic control who were growing well. Overnight GH profiles in the MS and normally growing diabetics were analyzed by the CLUSTER program. The mean 12-hour GH concentrations, pulse amplitude, and pulse frequency were not different in either group of patients and did not change during acute normalization of the serum glucose overnight in the MS patients. The GH-binding proteins (GHBPs) relative binding were found to be the same in both groups of patients and did not differ from normal nondiabetic sera (62% +/- 8.0% relative specific binding in MS patients, v 53% +/- 4.3% in diabetic controls). The IGF-I concentrations were normal and comparable in both groups of patients (1.1 +/- 0.1 U/mL MS, v 1.1 +/- 0.3 diabetic controls). The IGFBPs were comparable in both groups of patients as well. One of the patients with MS had no meaningful increase in his growth velocity after 1 year on GH therapy despite good compliance. In conclusion, our data show normal hypothalamic-pituitary function, normal GHBP, IGF-I generation, and IGFBPs in two patients with MS when compared with normally growing diabetic children. These data, and the lack of linear growth in response to exogenous GH therapy in one patient, suggest a GH-resistant state, either secondary to impaired bioactivity of IGF-I, or a defect at or distal to the IGF-I receptor.

Carrier Proteins↗
PubMed1991

Augmented hypothalamic proopiomelanocortin gene expression with pubertal development in the male rat: evidence for an androgen receptor-independent action.

To investigate the mechanism(s) during pubertal development by which androgens alter hypothalamic proopiomelanocortin (POMC) gene expression and beta-endorphin content, we used the technique of in situ hybridization histochemistry and the androgen-insensitive testicular feminized (Tfm) rat. We evaluated POMC mRNA levels in the arcuate nuclei and periarcuate regions of 12 coronal brain slices from prepubertal (age, 30 days) and adult (age, 60 days) normal male and Tfm rats (n = 4 for each group). Hybridizations were performed using an 35S-radiolabeled oligonucleotide probe complementary to a 30-base sequence within POMC mRNA. The tissue sections were sequentially exposed to x-ray film and photographic emulsion with subsequent analysis by both densitometry and computer-assisted grain counting. beta-Endorphin was measured in hypothalamic tissue blocks from similar animals in each of the four experimental groups. The results of densitometry and grain counting were consistent and revealed an increase in POMC mRNA with pubertal development in both the male and Tfm animals. The concentration of hypothalamic beta-endorphin was greater for the adult Tfm animals than for all other groups, which did not differ from each other. These results suggest that androgens may stimulate POMC gene transcription by their action through estrogen receptors after conversion by aromatase. Alternatively, additional pubertal factors may be responsible for act directly through their respective receptors to alter translation, posttranslational processing, or secretion of beta-endorphin, resulting in diminished intracellular hypothalamic peptide concentration.

Animals↗
PubMed1991

Growth hormone-binding protein activity is inversely related to 24-hour growth hormone release in normal boys.

To investigate the physiological relationship between serum GH-binding proteins and 24-h GH release, we compared the 24-h GH pulse attributes in serum samples obtained at 20-min intervals to the serum GH-binding protein activity (GH-BP) from 38 normal boys between 7 5/12 and 18 4/12 yr of age. GH-BP was determined in a serum sample from each study (containing less than 1.0 micrograms/L GH) using a standardized GH-BP assay. GH-BP results are expressed as the percentage of [125I]human GH bound to the high affinity GH-BP complex (peak II) per 160 microL serum. There were significant inverse relationships between the high affinity (receptor-related) GH-BP and several characteristics of 24-h GH release. Specifically, GH-BP was significantly (P less than 0.005 for all), but negatively, correlated with mean 24-h GH concentration (r = -0.62), sum of the GH pulse amplitudes (r = -0.57), sum of the GH pulse areas (r = -0.55), interpulse mean GH concentration (r = -0.53), and number of GH pulses per 24 h (r = -0.53). In addition, GH-BP correlated positively with the mean time interval between pulses (r = 0.59). There was also a significant positive correlation (r = 0.75; P less than 0.001) between GH-BP and the subject's age-adjusted body mass index SD score (BMI-SDS). Each characteristic of 24-h GH release correlating inversely with GH-BP also correlated inversely with BMI-SDS (P less than 0.01 for all comparisons). GH-BP did not, however, correlate with plasma insulin-like growth factor-I levels, serum testosterone concentrations, or height SDS. Binding to the low affinity GH-BP (peak I) did not correlate significantly with any of the examined GH pulse attributes, BMI-SDS, or the degree of binding to the high affinity GH-BP (peak II). We conclude that an inverse relationship exists between the high affinity serum GH-BP and 24-h GH release in boys under normal physiological conditions. We speculate that abnormalities in this relationship probably also exist and may underlie some disorders of growth.

Adolescent↗
PubMed1991

Estrogenic modulation of the gonadotropin-releasing hormone-stimulated secretory activity of the gonadotrope and lactotrope in prepubertal females with Turner's syndrome.

The nature of estrogen's modulation of GnRH-stimulated secretion of the female prepubertal gonadotrope and lactotrope was studied in nine girls with primary gonadal failure (Turner's syndrome; mean age, 10.0 +/- 0.25 yr). LH, FSH, and PRL release was evaluated by sampling blood every 20 min from 2000-0800 h. Hormone secretion was stimulated by one of two randomized doses of GnRH (50 or 750 ng/kg) delivered at fixed intervals of every 90 min in an attempt to replace the function of the endogenous GnRH pulse generator with an exogenous GnRH clamp. To evaluate the time dependency of estrogen action, studies were conducted at baseline and after 1 and 5 weeks of oral administration of ethinyl estradiol (EE; 100 ng/kg.day). In vivo gonadotropin secretory dynamics were quantitated by deconvolution mathematical modeling. We found a suppression of total LH secretion in response to repeated fixed doses of GnRH after 1 and 5 weeks of EE exposure, viz. a 10% (1 week) and 60% (5 weeks) reduction in the total mass of LH released after six consecutive GnRH pulses. Before estrogen exposure, patients manifested a decreasing mass of LH secreted per burst (slope of mass/burst vs. GnRH injection number was -3.3 +/- 1.44), suggesting down-regulation of the LH secretory response. However, after 5 weeks of EE treatment, the same series of GnRH doses elicited a progressive increase in the mass of LH secreted per burst (slope, 1.06 +/- 0.036; P = 0.041). Such serial amplification of LH secretory responses (despite overall suppression of the mean serum LH concentrations by EE) is consistent with the emergence of priming of GnRH actions. This phenomenon was specific, since the half-life of LH and the LH secretory burst duration were not altered. FSH responses to GnRH were significantly suppressed after 5 weeks of EE exposure (mean serum FSH concentrations, 61.9 +/- 11.4 IU/L at baseline vs. 14.4 +/- 6.9 at week 5; P = 0.003). However, in contrast to the LH responses on a given study day, there was increased FSH responsivity to successive doses of GnRH, suggesting a priming effect of serial GnRH exposure on GnRH-stimulated FSH secretion regardless of the estrogen milieu. PRL secretion was stimulated by GnRH at baseline (16.8 +/- 0.88 micrograms/L), but release was reduced at week 5 on estrogen (11.6 +/- 0.4 micrograms/L). This may represent withdrawal of the paracrine effects of endogenous GnRH and/or increased dopaminergic tone induced by estrogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Clinical utility of cycle exercise for the physiologic assessment of growth hormone release in children.

The clinical utility of exercise as a stimulus for the physiologic assessment of growth hormone (GH) deficiency was examined in healthy children. In response to exercise tests performed on different days, serum GH concentrations exceeded 7 micrograms/L on both days in 9 of 10 children. Although there is variation in this method of physiologic testing in the response of serum GH concentration (significant mean differences in GH peak values, 27.1 vs 19.8 micrograms/L for the two tests), the exercise test proved clinically valid in that diagnostic levels of GH were exceeded on both days 90% of the time. We conclude that this exercise evaluation protocol has clinical utility for the assessment of GH deficiency in children.

Adolescent↗