Glucocorticoids: Potent Inhibitors and Stimulators of Growth Hormone Secretion*

Wehrenberg, William B.; Janowski, Bethany A.; Piering, Andrew W.; Culler, Floyd L.; Jones, Kathryn L.

doi:10.1210/endo-126-6-3200

Cited by 153 publications

(83 citation statements)

References 27 publications

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“…In rats, spontaneous GH levels were significantly decreased and the GH-releasing hormoneinduced GH response was blunted after 4 d of DEXA treatment. Subsequent immunologic neutralization of somatostatin, however, resulted in a significantly enhanced GH response, suggesting that steroids inhibit the GH response to GHreleasing hormone by increasing the hypothalamic somatostatin secretion (27). Miell et al (34), however, found in healthy volunteers a persistent but attenuating rise in serum GH levels after 4 d of DEXA treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Inasmuch as we present the first data of an acute DEXA effect on serum GH levels in preterm infants, we cannot compare our results with other studies in preterm infants. In older individuals the effects of glucocorticoids on spontaneous and stimulated GH secretion appear contradictory (25)(26)(27). Chronic hypercortisolism inhibits spontaneous and stimulated GH secretion in children and adults (9 -11, 28).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Huysman

Hokken-Koelega

Hop³

et al. 2003

Pediatr Res

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Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9 -32.0 wk), median (range) birth weight 970 g (610 -2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) -1 and -3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 g/L (6 -28.4 g/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 g/L (1.7-11.9 g/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p Ͻ 0.01, p Ͻ 0.01, and p Ͻ 0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p Ͻ 0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found. Very preterm infants developing BPD, with a persistent need for artificial ventilation and oxygenation, frequently show a very compromised growth in the neonatal period (1, 2). Their growth will be further attenuated when DEXA treatment is given after conservative treatment, including increased ventilation settings and fluid restriction, has failed to wean them from the ventilator (3-5). The hormonal mechanisms underlying this early postnatal growth retardation and the role of glucocorticosteroids have not been elucidated. DEXA has a catabolic effect by increasing protein breakdown and alters skeletal metabolism by inhibition of intestinal calcium absorption, stimulation of renal calcium excretion, and suppression of collagen turnover in preterm infants (6 -8).Glucocorticosteroids have been suggested to have a suppressive effect on the pituitary GH secretion with attenuation of the spontaneous GH secretion and decreased GH responses to various stimuli (9 -11). A direct antagonizing effect of DEXA on the epiphyseal cartilage to the action of GH has been reported, probably by inhi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Huysman

Hokken-Koelega

Hop³

et al. 2003

Pediatr Res

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“…hexarelin remain responsive to subsequent GHRH stimulation (L K Conley, R C Gaillard, A Giustina, R S Brogan & W B Wehrenberg, unpublished observations) and others have reported a maintained responsiveness to GHRH or the opiate agonist MRZ 2549 during continuous GHRP-6 exposure (Sartor et al 1985b, Clark et al 1989. In addition, although others have reported increases in cortisol in response to intermittent GHRP-6 treatment in man (Hayashi et al 1991, Frieboes et al 1995, Thomas et al 1997), a sustained increase in this inhibitor of GH secretion (Wehrenberg et al 1990) is an unlikely explanation, as we found that corticosterone concentrations were not significantly elevated in response to long-term exposure to hexarelin (Fig. 4A).…”

Section: Figure 3 (A)mentioning

confidence: 98%

Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats

Conley

Gaillard²,

Giustina³

et al. 1998

Journal of Endocrinology

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We have previously shown that hexarelin, a novel GHreleasing peptide (GHRP), is able to elicit GH release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the effects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats.In the first experiment, adult male Sprague-Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 µg/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the mean ... For both the peak and AUC results there was a significant (P<0·05) difference in the GH response noted between the first (peak 301 37 ng/ml; AUC 5585 700 ng/ml per 30 min) and second (peak 149 47 ng/ml; AUC 3056 908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214 49 ng/ml; AUC 3862 844 ng/ml per 30 min). In a second series of experiments, adult male Sprague-Dawley rats received continuous infusions (100 µg/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not differ between any of the treatment groups, nor did any of the parameters of pulsatile hormone release analyzed. No significant differences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941 70 ng/ml) nor the 30 h (954 70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935 65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289 42 ng/ml; P<0·05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of pulsatile GH release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

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“…Many lines of evidence suggest that hypothalamic somatostatin (SRIF) is chiefly responsible for GC-induced CH suppression [11][12][13].…”

mentioning

confidence: 99%

Effects of Short- and Long-Term Dexamethasone Treatment on Growth and Growth Hormone (GH)-Releasing Hormone (GRH)-GH-Insulin-Like Growth Factor-l Axis in Conscious Rats.

et al. 1997

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Abstract. Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily ip injections of DEX (200 µg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed.Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.

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Glucocorticoids: Potent Inhibitors and Stimulators of Growth Hormone Secretion*

Cited by 153 publications

References 27 publications

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats

Effects of Short- and Long-Term Dexamethasone Treatment on Growth and Growth Hormone (GH)-Releasing Hormone (GRH)-GH-Insulin-Like Growth Factor-l Axis in Conscious Rats.

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