Paradoxical Enhancement of Pituitary Growth Hormone (GH) Responsiveness to GH-Releasing Factor in the Face of High Somatostatin Tone*

Tannenbaum, Gloria Shaffer; Painson, Jean-Claude; Lengyel, A. M. J.; Brazeau, Paul

doi:10.1210/endo-124-3-1380

Cited by 74 publications

(41 citation statements)

References 38 publications

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“…Th e augme nted GH responsiveness to GRF reported here differs from our earli er observatio n of diminish ed GRFinduced GH rele ase in rats fed a low prot ein diet in adult life (16), but resembles the paradoxic al enhanceme nt of GH respo nsiveness to GRF found in foo d-deprived adult rats that exhibit high SRIF ton e (26) . Thus, an increased SRIF influence on pituitary somatotrophs could provide an additional expl anati on for the suppress ion in GH pulse amplitude and the enhance d GH response to GRF th at we obs erved in adult rats ex pose d to protein deprivation in ea rly life.…”

contrasting

confidence: 91%

Long-Term Alterations in Growth Hormone and Insulin Secretion after Temporary Dietary Protein Restriction in Early Life in the Rat

Harel

Tannenbaum

1995

Pediatr Res

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Protein malnutrition early in life stunts subsequent physical growth in both humans and rats, but the mechanism(s) is unknown . To test the hypothesis that temporary early life dietary protein restriction produces long-term alterations in the grow th hormone (GH) neuroendocrine axis, we examined the effects of 3 wk of exposure to dietary protein restriction in male rats postwea ning (3-6 wk of age) on spontaneous and GH-releasing factor (GRF)-stimulated GH secretion at 12 wk of age. In compar ison to rats weaned onto a normal diet (23% protein), rats weaned onto a low (4%) protein diet failed to catch up growth when transferred to the normal diet between 6 and 12 wk of age. Spontaneous 6-h GH secretory profiles of adult rats fed the low protein diet early in life showed a 41% reduction in mean GH peak amplitude and a significant suppression in overall mean 6-h plasma GH concentra tions (37.5 ± 4.5 versus 56.9 ± 5.9 J.Lg/L; p < 0.02). The magnitude of the GH response to 1 J.Lg of rat GRF(I-29)NH 2 i.v. challenge was augmented during the GH trough period in these rats (165.7 ± 30.4 versus 43.9 ± 17.6 J.Lg/L; P < 0.01). Although basal plasma lGF-l levels and glucose tolerance of protein-deprived rats were normal at 12 wk of age, the insulin response to ip glucose was severely blunted [insulin Undernutrition in early life impairs subsequent physical growth in both humans (1-4) and rats (5), but the mechanism (s) is not yet known. Exposure to early postnatal undernutrition, in genera l, and protein malnutritio n, in particular, has deleterious effects on the development and func tion of various organs, and leads to lower protein/DNA ratios in several tissues (5-10). Such persisting cellular hypoplasia may result in insufficient cellular machi nery for hormonal biosynthesis.

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contrasting

confidence: 91%

Long-Term Alterations in Growth Hormone and Insulin Secretion after Temporary Dietary Protein Restriction in Early Life in the Rat

Harel

Tannenbaum

1995

Pediatr Res

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“…Nonetheless, given that sst2A is the predominant sst subtype in the PIT and is clearly linked to the inhibitory effect of SST on GH release (34), downregulation of PIT sst2A, coupled with reduced HPT SST input, could represent a primary mechanism by which GH levels increase in response to fasting. The fact that fasting-induced downregulation in PIT sst2/sst5 expression has been observed in male rats (8,34,47) and nutrient deprivation has been shown to decrease the GH response to exogenous SST administration in rats, dogs, and humans (33,52,59,60,63) suggests that the fasting-induced changes in PIT responsiveness to SST is preserved across species. The mechanism by which these changes occur may be directly related to the well-characterized reduction in circulating IGF-I and rise in glucocorticoids observed with fasting (Ref.…”

Section: Resultsmentioning

confidence: 99%

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

Córdoba-Chacón

Gahete

Castaño

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Córdoba-Chacón J, Gahete MD, Castaño JP, Kineman RD, Luque RM. Somatostatin and its receptors contribute in a tissuespecific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice. Am J Physiol Endocrinol Metab 300: E46 -E54, 2011. First published October 13, 2010; doi:10.1152/ajpendo.00514.2010.-Somatostatin (SST) inhibits growth hormone (GH) secretion and regulates multiple processes by signaling through its receptors sst1-5. Differential expression of SST/ssts may contribute to sex-specific GH pattern and fastinginduced GH rise. To further delineate the tissue-specific roles of SST and sst1-5 in these processes, their expression patterns were evaluated in hypothalamus, pituitary, and stomach of male and female mice under fed/fasted conditions in the presence (wild type) or absence (SST-knockout) of endogenous SST. Under fed conditions, hypothalamic/stomach SST/ssts expression did not differ between sexes, whereas male pituitary expressed more SST and sst2A/2B/3/5A/ 5TMD2/5TMD1 and less sst1, and male pituitary cell cultures were more responsive to SST inhibitory actions on GH release compared with females. This suggests that local pituitary SST/ssts can contribute to the sexually dimorphic pattern of GH release. Fasting (48 h) reduced stomach sst2A/B and hypothalamic SST/sst2A expression in both sexes, whereas it caused a generalized downregulation of pituitary sst subtypes in male and of sst2A only in females. Thus, fasting can reduce SST sensitivity across tissues and SST input to the pituitary, thereby jointly contributing to enhance GH release. In SST-knockout mice, lack of SST differentially altered sst subtype expression levels in both sexes, supporting an important role for SST in sex-dependent control of GH axis. Evaluation of SST, IGF-I, and glucocorticoid effects on hypothalamic and pituitary cell cultures revealed that these hormones could directly account for alterations in sst2/5 expression in the physiological states examined. Taken together, these results indicate that changes in SST output and sensitivity can contribute critically to precisely define, in a tissue-dependent manner, the sex-specific metabolic regulation of the GH axis.

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“…In fasting rats a significant decrease of SS receptor mRNA expression, which sensitizes the pituitary responsiveness to an ensuing GHRH stimulus, has been reported (Tannenbaum et al 1989, Bruno et al 1994. This event, however, is probably due to a fasting-induced activation of hypothalamic somatostatinergic function and downregulation of pituitary receptors, since in the rat fasting suppresses GH secretion (Tannenbaum & Rorstad 1979, Bruno et al 1994.…”

Section: Discussionmentioning

confidence: 96%

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine

Rigamonti¹,

Marazzi²,

Cella³

et al. 1998

Journal of Endocrinology

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Using unanesthetized young male and female beagle dogs, before and after a 2-day fast, we studied the effect of an i.v. infusion of 0·9% saline (5 ml/h), somatostatin (SS, 4 or 8 µg/kg/h) or pretreatment with pirenzepine (PZ, 0·6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS, on the GH release evoked by acute administration of GHRH (2 µg/kg i.v.), hexarelin (HEXA), a member of the GH-releasing peptide family (250 µg/kg i.v.) or GHRH plus HEXA.In fasted dogs, GHRH delivered during saline infusion induced a clear-cut rise in plasma GH levels, significantly higher than that which it induced in fed dogs. In contrast, HEXA, although very effective in causing the release of GH, only slightly increased GH secretion in fasted dogs over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into fed dogs induced a synergic GH response that further increased with fasting.The action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at either dose was ineffective in suppressing the GH-releasing effect during fasting. Infusion of the lower dose of SS failed to counter the action of HEXA, either before or during fasting, whilst the higher SS dose partially reduced it in both conditions.In contrast to SS, PZ reduced the GH-releasing effect of GHRH and HEXA, both in the fed state and, though to a lesser extent, during fasting. Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA in fed dogs. The suppressive effect of PZ on the GH response to combined administration of the peptides was lowest in fasted dogs.These data show that: (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA; (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted state; (3) only the higher dose of SS partially reduced the GH stimulation by HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5) PZ did not modify the GH release due to the combined administration of GHRH and HEXA.It is suggested that: (1) during fasting the greatly enhanced GH response to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion; (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion in states of calorie deprivation; (3) in contrast to a general belief, muscarinic cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but probably also through inhibition of GHRH function.

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Paradoxical Enhancement of Pituitary Growth Hormone (GH) Responsiveness to GH-Releasing Factor in the Face of High Somatostatin Tone*

Cited by 74 publications

References 38 publications

Long-Term Alterations in Growth Hormone and Insulin Secretion after Temporary Dietary Protein Restriction in Early Life in the Rat

Long-Term Alterations in Growth Hormone and Insulin Secretion after Temporary Dietary Protein Restriction in Early Life in the Rat

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine

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