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Biomedical subjects

M O Thorner

Publications and source records attributed to M O Thorner.

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

Growth hormone and nutrition.

The regulation of growth hormone (GH) secretion in humans is a complex process which comprises more than stimulation by GH-releasing hormone and suppression by somatostatin. Although these two hypothalamic hormones are the primary regulators of GH secretion, they most likely function as the final pathway through which numerous factors influence GH synthesis and secretion. Some of the modulators of GH secretion include neurotransmitters, circulating glucose, insulin-like growth factor I and gonadal steroid concentrations. Age, nutrition and body composition are also related to the amount and pattern of GH secretion in humans. The influence of nutritional status on GH secretion is becoming more clearly defined.

Adult↗
PubMed1992

Short-term adult exposure to estradiol feminizes the male pattern of spontaneous and growth hormone-releasing factor-stimulated growth hormone secretion in the rat.

Experimental evidence indicates that the neonatal gonadal steroid environment is an important determinant of the sexual dimorphism of GH secretion and body growth. However, the influence of the sex steroids in GH control during adult life and their mechanism/site of action are largely unknown. In the present study we examined the effects of adult gonadectomy (GNX) and short term adult exposure to 17 beta-estradiol (E2) on both spontaneous and GRF-stimulated GH release in free-moving adult male rats. The rate of body weight gain was also monitored. GNX (3 weeks postoperatively) resulted in a 2-fold reduction in GH pulse amplitude compared to that in sham-operated control rats, but did not significantly alter the GH nadir or the interpeak interval. Exposure to E2 (sc implants) for 4 days markedly disrupted the spontaneous GH secretory profile of both sham-operated and GNX rats; E2-treated animals exhibited a striking elevation (4- to 20-fold) of GH trough levels and a significant decrease in GH interpeak interval, remarkably similar to the typical female rat GH secretory profile. The augmentation in both GH nadir and GH pulse frequency was evident as early as 12 h after a single sc injection of E2 valerate. In sham and GNX rats bearing control implants, the GH response to 1 micrograms rat GRF-(1-29)NH2, iv, was significantly greater when GRF was administered at peak (1100 h) than at trough (1300 h) times of GH secretion; the latter is known to be due to antagonism by the cyclical increased release of endogenous somatostatin (SRIF) in the male rat. Treatment with E2 abolished this time-dependent difference in both groups and produced a regular pattern of GH responsiveness to GRF similar to that typically observed in the female rat, thus suggesting that E2 has altered the pattern of hypothalamic SRIF secretion from a cyclic to a more continuous mode of release. Chronic exposure to E2 for 2 weeks resulted in an almost 6-fold inhibition of the rate of body weight gain in sham-operated male rats to levels comparable to those in normal adult female rats. Taken together, these results demonstrate that short term exposure to E2 during adult life can profoundly feminize the male pattern of spontaneous and GRF-stimulated GH secretion, as well as rate of somatic growth.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors.

GH secretion has been thought traditionally to be regulated by the two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin (SRIF). Recent evidence has suggested that other factors may be involved. These factors include the natural ligand for the synthetic hexapeptide GH-releasing peptide (GHRP) and the putative hypophysiotropic factor pituitary adenylate cyclase-activating polypeptide (PA-CAP). Accordingly, we examined the effects of GHRP and PACAP on GH secretion at the single cell level using the reverse hemolytic plaque assay which allows distinction of effects on the number of secreting cells and the amount of hormone each cell secretes. Both factors stimulated GH secretion in a dose-dependent fashion, with PACAP being more effective. PACAP increased both the number of cells secreting and the mean amount of hormone secreted per cell. In contrast, GHRP increased the number of secreting cells, although it had no effect on the amount of secretion per cell. GH secretion induced by GHRH, GHRP, and PACAP was inhibited by SRIF, but the effect was predominantly on the number of cells secreting rather than the amount secreted per cell. Specific antagonists to GHRP and GHRH inhibited GH secretion induced by the respective agonist but not that induced by the other factor nor by PACAP. These findings confirm the complex nature of the regulation of GH secretion at the level of the somatotrope. At least three factors, operating via distinct receptors, are able to increase GH secretion. In addition, they ascribe a potential physiological role for the hitherto putative hypophysiotropic factor PACAP.

Animals↗
PubMed1992

Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men.

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- 0.16 mg/m2 (assuming a distribution volume of 7.9% body weight), P = 0.0001]. This enhanced GH production rate was accounted for by 2-fold increases in the number of GH secretory bursts per 24 h (14 +/- 2.3 vs. 32 +/- 2.4, P = 0.0006) and the mass of GH secreted per burst (6.3 +/- 1.2 vs. 11 +/- 1.6 micrograms/Lv, P = 0.002). The latter was a result of increased secretory-event amplitudes (maximal rates of GH release attained within a burst) with unchanged secretory burst durations. GH was secreted in complex volleys composed of multiple discrete secretory bursts. These secretory volleys were separated by shorter intervals of secretory quiescence in the fasted than fed state (respectively, 88 +/- 4.2 vs. 143 +/- 14 min, P = 0.0001). Similarly, within volleys of GH release, constituent individual secretory bursts occurred more frequently during the fast [every 33 +/- 0.64 (fasted) vs. every 44 +/- 2.0 min (fed), P = 0.0001]. The t1/2 of endogenous GH was not significantly altered by fasting [18 +/- 2.2 (fasted) vs. 20 +/- 1.5 min (fed), P = 0.47]. Serum insulin-like growth factor I concentrations were unchanged after 56 h of fasting. In conclusion, the present data suggest that starvation-induced enhancement of GH secretion is mediated by an increased frequency of GHRH release, and longer and more pronounced periods of somatostatin withdrawal.

Adult↗
PubMed1992

Oral administration of growth hormone (GH)-releasing peptide stimulates GH secretion in normal men.

Intravenous infusions of the synthetic hexapeptide GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2; GHRP) specifically stimulate GH release in man. To determine whether orally administered GHRP stimulates GH secretion, 10 normal men received oral doses of placebo, 30, 100, and 300 micrograms/kg GHRP, and an iv injection of 1.0 micrograms/kg GHRP at weekly intervals in a single blind, randomized design. Serum GH concentrations were measured in blood samples obtained at 5-min intervals for 1 h (0700-0800 h) before and 4 h (0800-1200 h) after each dose. Mean (+/- SE) peak GH concentrations were 4.0 +/- 1.5, 5.2 +/- 1.6, 9.2 +/- 3.3, 18 +/- 3.7, and 26 +/- 5.6 micrograms/L for placebo; 30, 100, and 300 micrograms/kg oral GHRP; and 1 micrograms/kg iv GHRP, respectively; mean 4-h (0800-1200 h) integrated GH concentrations were 312 +/- 109, 406 +/- 159, 698 +/- 284, 1264 +/- 303, and 1443 +/- 298 min.micrograms/L, respectively. To analyze changes in the pulsatile pattern and amount of GH secretion after the administration of GHRP, a waveform-independent deconvolution method was used to estimate GH secretion rates. Variable increases in GH secretion after placebo and GHRP treatments were observed. Despite this variability, weighted least squares linear regression revealed that increasing doses of oral GHRP progressively stimulated GH secretion (P less than 0.005); similar relationships were observed for the peak GH concentration and 4-h integrated GH concentrations. The GH responses to oral GHRP (300 micrograms/kg) and iv GHRP (1 microgram/kg) were significantly greater than that to placebo (P less than 0.05) and were comparable in magnitude. Pairwise comparisons revealed that increases in GH concentrations and secretion rates after the 30 and 100 micrograms/kg oral doses of GHRP were not significantly different from those after placebo. The increase in GH secretion after GHRP treatment was accounted for entirely by an increase in the amplitude of GH secretory events, as no significant increase in the number of GH secretory pulses was observed. The onset and duration of action of GHRP were analyzed by a proportional hazards general linear regression model. Intravenous GHRP had a more rapid onset of action than all doses of oral GHRP (P less than 0.02). Increasing doses of oral GHRP resulted in earlier GH responses (P = 0.006). However, the duration of the GH response was similar for iv GHRP and all doses of oral GHRP, averaging 120-150 min.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1992

A quantitative estimation of growth hormone secretion in normal man: reproducibility and relation to sleep and time of day.

Recent reports, based on measurements of plasma GH levels, have challenged the concept that GH secretion is dependent on sleep and not modulated by circadian rythmicity. Because plasma levels reflect not only the secretory process, but also the effects of distribution and degradation, temporal limits of active secretion and, consequently, synchrony with other physiological events cannot be accurately estimated from circulating concentrations. The present study was undertaken to examine the roles of sleep and time of day in modulating pulsatile GH secretion, using a mathematical procedure (deconvolution) allowing secretory rates to be estimated from peripheral levels. Eight young nonobese healthy men participated each in six separate 16-h studies involving either normal or delayed sleep. Plasma GH levels were measured at 15-min intervals, and GH secretory rates were calculated by deconvolution. Each individual study was preceded by one night of habituation, and sleep was polygraphically recorded in all studies. Repeated measurements of plasma insulin-like growth factor-I (IGF-I) were performed in all subjects. Deconvolution revealed the existence of approximately 20% more GH pulses than detected in the plasma profiles. Large peaks of plasma GH concentrations often reflected the occurrence of a succession of secretory pulses. The total amount of GH secreted varied 10-fold across individual studies, but the within-subject variability (32%) was less than half the across-subject variability (65%). IGF-I levels were also more reproducible for a given subject than across subjects (11% vs. 36% variability) and did not correlate with the amount of GH secreted. During normal waking hours, the GH secretory rate was similar in the evening and the morning. This secretory rate was doubled during wakefulness at times of habitual sleep and tripled during sleep, even when sleep was delayed until 0400 h. A pulse starting within 30 min after sleep onset was present in all profiles with normal sleep and in 13 of 16 profiles with delayed sleep. The amount of GH secreted in response to sleep onset was tightly correlated with the level of secretion during wakefulness (r = 0.92). Almost 70% (57 of 83) of the pulses occurring during sleep were associated with slow wave (SW) stages. The amount of GH secreted in SW-associated pulses was correlated with the amount of SW occurring during the pulse, even when sleep-onset pulses were not considered. We conclude that in normal adult men, the amount of GH secretion and the levels of IGF-I are more reproducible within than across individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Sleep, awakenings, and insulin-like growth factor-I modulate the growth hormone (GH) secretory response to GH-releasing hormone.

To delineate possible factors influencing the magnitude of the GH response to GH-releasing hormone (GHRH), eight young healthy men participated in seven 16-h studies involving saline infusions or injections of 0.3 micrograms/kg GHRH at various times of day and stages of sleep. GH responses were quantified by deconvolution, a procedure allowing for secretory rates to be estimated from peripheral levels. While the plasma responses were monophasic, deconvolution revealed that the secretory response to GHRH generally included several distinct bursts in rapid succession. The intersubject variability of GH responses was very wide, but for a given subject, the response was quite reproducible (mean +/- SEM coefficient of variation, 21 +/- 3%). When GHRH was given during the waking period, the magnitude of the response was directly related to the amount of spontaneous GH secretion, negatively correlated with circulating levels of insulin-like growth factor-I (IGF-I) and was not influenced by time of day. When GHRH was given during slow wave sleep, the magnitude of the response was enhanced. When GHRH was given during rapid eye movement sleep, the response was similar to that observed during wake. Awakenings during sleep consistently inhibited the secretory response to GHRH, and resumption of sleep was associated with a reappearance of the secretory process. Thus, in normal men of similar age and body weight, the GH response to GHRH is dependent on the sleep or wake condition, circulating levels of IGF-I, and, possibly, genetic and lifestyle factors.

Adult↗
PubMed1991

A potential code of luteinizing hormone-releasing hormone-induced calcium ion responses in the regulation of luteinizing hormone secretion among individual gonadotropes.

Luteinizing hormone-releasing hormone (LHRH) induces two Ca2+ responses in single gonadotropes: a Ca2+ spike/plateau or oscillation. Similar receptor-mediated Ca2+ signals have been reported in many cell types but their functional significance is obscure. Accordingly, we have determined the concentration-response properties of LHRH-induced luteinizing hormone (LH) release at the single cell level. We demonstrate a critical single cell LHRH threshold for LH release. Each gonadotrope had a particular LHRH threshold value and a range of different single cell thresholds was distributed in the gonadotrope population. The physiological significance of the threshold was demonstrated by a striking reduction (delta ED50 = 153 nM) of the LHRH threshold immediately before the preovulatory surge of LH release. The metestrous phenotype of secretion resembled a quantal process in contrast with the graded process of the proestrous phenotype. That is, the quantity of hormone secreted per metestrous gonadotrope was independent of LHRH concentration and more all-or-none than graded. The LHRH threshold and the quantal secretion process of metestrous gonadotropes was further studied by measuring cytosolic Ca2+ using fura-2 and digital imaging microscopy. We provide evidence suggesting that the Ca2+ spike/plateau and oscillation are the respective responses to subthreshold and suprathreshold concentrations of LHRH. It is proposed therefore that the Ca2+ oscillation and spike/plateau response form a binary intracellular signaling code that functions as an on-off switch. It is further proposed that this potential code unraveled here for the regulation of hormone secretion may also regulate other gonadotrope functions. Thus, while the Ca2+ spike/plateau response is strongly associated with LH release, it may be associated with reduced levels of LH-beta mRNA, and reduced numbers of LHRH receptors. Conversely, while the Ca2+ oscillation appears to be unrelated to LH release, it may be associated with increased levels of LH-beta mRNA, and increased numbers of LHRH receptors. This model may explain in molecular terms the long-standing observation that an invariant, albeit pulsatile, pattern of LHRH release is sufficient to support the preovulatory surge of LH release.

Animals↗
PubMed1991

Temporal structure of in vivo growth hormone secretory events in humans.

The time course of spontaneous growth hormone (GH) secretion was studied in 12 normal men by analyzing serum GH concentrations measured in blood collected at 5-min intervals over 24 h with a multiple-parameter deconvolution model to simultaneously resolve endogenous GH secretory and clearance rates. Twenty-four-hour profiles of serum GH concentrations were accounted for by an average of 12 +/- 1.2 (SE) discrete GH secretory bursts having a mean half-duration (duration at half-maximal amplitude) of 25 +/- 2.3 min, indicating that 95% of daily GH secretion occurred in 8.8 h. The majority (96%) of GH was secreted in volleys composed of multiple (4.0 +/- 0.4) discrete secretory bursts. Such volleys of GH secretion were separated by 171 +/- 19 min, whereas their constituent individual secretory events occurred every 36 +/- 1.7 min (P = 0.0001). Between secretory volleys, calculated GH secretory rates fell asymptotically to zero. Significant positive and negative autocorrelations were observed for the series consisting of successive GH secretory burst mass and interburst intervals, respectively. Linear regression analysis revealed significant negative correlations between the mass of GH secreted per burst and both the preceding and following interburst intervals. Estimates of the half-life of endogenous GH (17 +/- 1.7 min) and of the endogenous GH production rate (0.25 +/- 0.033 mg/m2 for an assumed distribution volume of 7.9% body wt) agreed well with earlier independent measurements. We conclude that the human pituitary gland secretes GH in volleys consisting of multiple secretory bursts, without measurable intervening tonic secretion. This pattern of in vivo GH release in normal humans is consistent with a model of high-frequency GH-releasing hormone secretory events superimposed on low-frequency episodes of somatostatin withdrawal.

Adult↗
PubMed1991

Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages.

Both fasting and sleep increase the secretion of human GH and, therefore, might explain its predominantly nocturnal release. To study the precise temporal relationship between GH secretory episodes and cortical activity, GH measurements and electroencephalogram sleep stage recordings were performed every 30 s for 8 h in six young male volunteers fasted for 24 h. GH was measured in two drops of whole blood, which were directly sampled into the assay tube using a continuous blood withdrawal pump and a fraction collector. Concomitant serum sampling during a GH-releasing hormone test (n = 4) revealed a high correlation (r = 0.98) between GH measurements in serum and whole blood. GH pulses were objectively identified with Cluster analysis, and GH secretion rates were calculated with a waveform-independent deconvolution algorithm. When data were analyzed as replicates with 1-min intervals, the nocturnal pulse frequency was 1.2 pulses/h. Elimination of data points demonstrated 43% and 64% reductions in the number of GH pulses detected for 5- and 20-min sampling intervals, respectively. Mean GH concentrations and secretory rates were significantly higher during stage 3 and 4 sleep compared to stage 1, 2, and rapid eye movement sleep. GH secretory rates and peripheral GH concentrations were maximally correlated with sleep stage, with lags of 4.5 and 16 min, respectively, suggesting that maximal GH release occurs within minutes of the onset of stage 3 or 4 sleep. This temporal coincidence between pituitary GH secretion and delta sleep is consistent with cortical control over hypothalamic-pituitary function.

Adult↗
PubMed1991

Growth hormone (GH) secretion during continuous infusion of GH-releasing peptide: partial response attenuation.

The synthetic hexapeptide GH-releasing peptide (GHRP; SK&F 110679) specifically stimulates GH release in man. To determine the effect of a continuous GHRP infusion and whether response attenuation occurs in man, we administered to six healthy subjects a 6-h infusion of saline and three doses of GHRP, each followed by a 1.0 micrograms/kg bolus injection. GH was measured every 10 min using an immunoradiometric assay. During the saline infusion, spontaneous GH peaks occurred at variable times in four of the six subjects. During the continuous GHRP infusion, a single burst of GH release occurred with the two lower doses (0.1 and 0.3 micrograms/kg.h). With the highest dose of 1.0 micrograms/kg.h, a primary burst of GH release was followed by sporadic secretory episodes of lesser magnitude during the infusion; the GH concentrations remained above baseline before administration of the iv GHRP bolus in all six subjects. The mass of GH secreted was indirectly determined using waveform-independent deconvolution analysis. Mean GH secretion rates (micrograms per L distribution volume/h) were calculated by dividing the GH mass by the time interval. The GH secretion rates during the infusion period (0900-1430 h) were 2.40 +/- 0.68, 2.47 +/- 0.61, 7.67 +/- 1.86, and 14.75 +/- 2.32 on the saline and GHRP (0.1, 0.3, and 1.0 micrograms/kg.h) infusion days, respectively (P less than 0.05, 1.0 micrograms/kg.h vs. saline). The GH secretion rates after the iv GHRP bolus were 18.28 +/- 3.81, 19.01 +/- 2.03, 11.70 +/- 2.55, and 7.86 +/- 0.80 on the saline and GHRP (0.1, 0.3, and 1.0 micrograms/kg.h) infusion days, respectively (P less than 0.05, 1.0 micrograms/kg.h vs. saline). Compared with the saline infusion, the GH response to GHRP infusions was dose dependent (r = 0.81; P less than 0.001). The GH response to the iv bolus was inversely related to the dose of the preceding 5.5-h continuous GHRP infusion (r = -0.58; P = 0.003), and the total amount of GH secreted (constant infusion plus the bolus infusion periods) was not different among the GHRP doses. Constant GHRP infusion stimulates GH release in man, and partial response attenuation occurs with a subsequent 1.0 micrograms/kg GHRP bolus. We hypothesize that GHRP is active at multiple sites and may act as a functional somatostatin antagonist. Further studies are needed to better determine the site(s) of GHRP action and its potential use as a diagnostic and therapeutic agent.

Adult↗
PubMed1991

Preoperative diagnosis of acromegaly by growth hormone-releasing factor radioimmunoassay.

Acromegaly was diagnosed in a 37-year-old woman with classical physical and biochemical findings; an enlarged sella on computed tomography suggested the presence of a pituitary macroadenoma. Radiologic evidence of a lung mass prompted radioimmunoassay of plasma growth hormone-releasing factor (7,500 pg/ml; normal less than 100 pg/ml). After resection of a bronchial carcinoid, which stained positive for growth hormone-releasing factor, circulating growth hormone-releasing factor levels normalized. Subsequently, her clinical, biochemical, and radiologic evidence for acromegaly resolved. This case represents the first reported use of the human pancreatic growth hormone-releasing factor 1-40 radioimmunoassay to preoperatively diagnose this rare etiology of acromegaly.

Acromegaly↗
PubMed1990

Physiological role of somatostatin on growth hormone regulation in humans.

Growth hormone (GH) secretion in man is pulsatile and this pattern is regulated by both GH-releasing hormone (GHRH) and somatostatin. A large body of experimental evidence in both man and animals supports the model that bursts of GH secretion are mediated by a reduction of tonic hypothalamic somatostatin secretion. Our studies have been performed in normal subjects with frequent blood sampling for GH measurements (from 20-minute to 30-second intervals); the data have been analyzed by computer algorithms to objectively determine pulse characteristics and, in some studies, to estimate both pituitary secretion and clearance rates using deconvolution analysis. The studies include profiles of GH secretion in normal men and women in fed and fasted states; analysis of GH secretion during sleep; and administration of GHRH during different stages of sleep and after sleep deprivation. The variable GH response to exogenous GHRH and the attenuated response after 6 hours of GHRH infusion to GHRH, while not to hypoglycemia, as well as the pulsatile profile of GH secretion in response to continuous GHRH infusions (24 hours to 14 days), all support the thesis that it is hypothalamic somatostatin that determines the timing of bursts of GH secretion. This is further confirmed by the profile of GH secretion in a patient with ectopic GHRH secretion. Recently, we have initiated studies with the novel synthetic GH releasing hexapeptide, HisDTrpAlaTrpDPheLysNH2 (GHRP). Our studies show that it acts synergistically with GHRH. Several lines of evidence suggest that GHRP stimulates GH secretion independently of GHRH receptors and acts at both the hypothalamic and pituitary levels. It may act to functionally antagonize somatostatin.

Amino Acid Sequence↗
PubMed1990

Correlation study of serum prolactin levels, pituitary weights, number and ultrastructure of pituitary lactotrophs in female Long-Evans rats.

Twenty-five female, 23-month-old Long-Evans rats were sacrificed for investigation of correlations between serum prolactin levels, pituitary weights, numbers and ultrastructural features of pituitary lactotrophs. Serum prolactin levels measured by radioimmunoassay varied from 7.1 ng/ml to 1,534.0 ng/ml. Pituitary weights ranged from 16.0 mg to 255.0 mg. Serum prolactin levels were increased when pituitary weights were high; statistical analysis revealed a correlation between the two. No significant correlation was evident between serum prolactin levels and lactotroph percentage and ultrastructure. Light microscopy revealed a large number of lactotrophs in almost every pituitary. Values for nuclear, cell and cytoplasmic areas, nuclear/cytoplasmic ratios and nucleolar diameters remained similar in the lactotrophs of all animals. Electron microscopy disclosed no lactotroph damage or vascular injury. Ultrastructural morphometry of lactotrophs in the pituitaries studied showed no major differences in cytoplasmic volume densities of endoplasmic reticulum, Golgi complex, mitochondria, secretory granules and lysosomes as well as secretory granule diameters. It is reasonable to conclude that elevations of serum prolactin levels are due to an increase in pituitary mass, resulting from accumulation of lactotrophs. Thus hyperprolactinemia appears to be secondary to an increase in the number of lactotrophs and not hyperactivity of individual cells.

Animals↗
PubMed1990

Atenolol enhances nocturnal growth hormone (GH) release in GH-deficient children during long term GH-releasing hormone therapy.

The effect of the selective beta 1-adrenergic blocking agent atenolol (50 or 100 mg, orally) on spontaneous and GH-releasing hormone (GHRH)-stimulated GH release was evaluated in six GH-deficient children during long term therapy with GHRH. Nocturnal GH concentrations were determined every 20 min for 12 h under the following four conditions: 1) control, 2) atenolol administration only, 3) sc GHRH administration only, and 4) combined GHRH and atenolol administration. The mean 12-h nocturnal GH concentrations after administration of atenolol alone [2.4 +/- 0.6 microgram/L (mean +/- SEM)] or GHRH alone (2.7 +/- 1.0 micrograms/L) were indistinguishable from baseline values (2.0 +/- 0.5 microgram/L; P greater than 0.05). In contrast, the addition of atenolol to ongoing GHRH therapy caused a clear augmentation of 12-h overnight GH release compared to that during all other study periods (5.0 +/- 1.3 micrograms/L; P less than 0.05). In a subset of three subjects for whom GH pulse characteristics were determined, the primary mode of the enhanced GH release was through an increase in the amplitude of serum GH pulses. These results are consistent with the hypothesis that beta-adrenergic blocking compounds enhance the responsivity of the pituitary gland to agents that permit GH release by inhibiting hypothalamic somatostatin secretion or action. They suggest that atenolol may have potential as an adjunctive therapy in some children with abnormalities of GH secretion when GHRH is the primary therapeutic agent.

Age Determination by Skeleton↗
PubMed1990

Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone.

The acute GH release stimulated by the synthetic hexapeptide, His-DTrp-Ala-Trp-DPhe-Lys-NH2 [GH releasing peptide (GHRP)], was determined in 18 normal men and compared with the effects of GH-releasing hormone, GHRH-(1-44)-NH2. Specificity of effect was assessed by measurement of serum PRL, LH, TSH, and cortisol. GHRP was administered at doses of 0.1, 0.3, and 1.0 microgram/kg by iv bolus. GHRH at a dose of 1.0 microgram/kg was administered alone and together with various does of GHRP. No adverse clinical effects of laboratory abnormalities were observed in response to GHRP. A side-effect of mild facial flushing of 1- to 3-min duration occurred in 16 of the 18 subjects who received GHRH-(1-44)-NH2. Mean (+/- SEM) peak serum GH levels after injection of placebo and 0.1, 0.3, and 1.0 microgram/kg GHRP were 1.2 +/- 0.3, 7.6 +/- 2.5, 16.5 +/- 4.1, and 68.7 +/- 15.5 micrograms/L, respectively. The submaximal dosages of 0.1 and 0.3 microgram/kg GHRP plus 1 microgram/kg GHRH stimulated GH release synergistically. Serum PRL and cortisol levels rose about 2-fold above basal levels only at the 1 microgram/kg dose of GHRP, and there were no changes in serum LH and TSH over the first hour after administration of the peptide(s). GHRP is a potent secretagogue of GH in normal men. Since GHRP and GHRH together stimulate GH release synergistically, these results suggest that GHRP and GHRH act independently. This supports our hypothesis that the GH-releasing activity of GHRP reflects a new physiological system in need of further characterization in animals and man.

Adult↗