Noradrenergic and Dopaminergic Regulation of GH and Prolactin in Baboons

Steiner, Robert A.; Illner, Pavel; Rolfs, A; Toivola, P. T. K.; Gale, C

doi:10.1159/000122766

Cited by 15 publications

(7 citation statements)

References 34 publications

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“…These observations extend earlier findings in monkeys with other dopamine-|l-hydroxylase inhibitors [10]. Sponta neous GH secretion was markedly suppressed by DDTC; both the frequency and amplitude of the GH peaks were significantly diminished when compared to baseline levels.…”

Section: Discussionsupporting

confidence: 89%

“…This indicates that DDTC not only abolishes GH release by blocking NE synthesis but also that its action may, in part, be mediated by an increase of endogenous SS release. The intrahypothalamic dopamine increase may account for the SS release; in other settings dopamine has been shown to stimulate SS release [19][20][21], and dopamine administration into the medial basal hypothalamus has been shown to re duce GH release in young baboons [10], GHRH acts directly at the pituitary level, but its effects can be inhibited noncompetitively by SS, even when GHRH is given at a maximally stimulating dose [18]. The diminution of GH responses to GHRH after DDTC thus points to a possible effect of DDTC to increase endogenous SS.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that the administration of catecholamine precursors, such as ¿-dopa, increases dopamine and NE content in rat brain [6] and stimulates GH secretion in monkeys [7] and humans [8]. Conversely, inhibition of catechol amine synthesis decreases GH levels [6,9,10]. In the rat, dieth yldithiocarbamate (DDTC), a dopamine-fi-hydroxylase inhi bitor, has been shown to be an effective blocker of both NE synthesis [6][7][8] and GH secretion [6,8,11].…”

mentioning

confidence: 99%

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Effects of Inhibition of Norepinephrine Synthesis on Spontaneous and Growth Hormone-Releasing Hormone-Induced GH Secretion in Cynomolgus Macaques: Evidence for Increased Hypothalamic Somatostatin Tone

et al. 1990

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To define the role of noradrenergic regulation of growth hormone (GH) secretion in a primate species, spontaneous and GH-releasing hormone (GHRH) stimulated GH secretion was studied in 6 chronically catheterized adult male cynomolgus monkeys before and after inhibition of norepinephrine synthesis. Blood samples were obtained at 15-min intervals during an 8-hour period to characterize the pattern of GH secretion, and the GH response to GHRH, 10 µg/kg i.v., was determined. These measurements were repeated 2 weeks later, 2 h after the intravenous administration of 12.5 mg/kg of the dopamine-β-hydroxylase inhibitor diethyldithiocarbamate (DDTC), which has been shown to be an effective norepinephrine synthesis inhibitor in the rat. Spontaneous and stimulated GH secretory patterns before and after DDTC administration were compared. Both the frequency and the amplitude of spontaneous GH pulses were markedly reduced by DDTC [3.8 ± 0.4 before vs. 1.8 ± 0.4 peaks/8 h after DDTC (p < 0.005) and 5.5 ± 0.7 vs. 2.0 ± 0.6 ng/ml (p < 0.01)]. Areas under the curve were also reduced by DDTC treatment [10.8 ± 1.0 vs. 5.7 ± 1.1 ng · h/ml (p < 0.01)], and DDTC administration diminished the peak GH responses to GHRH [12 ± 6 vs. 4 ± 2 ng/ml (p < 0.05)]. These results are consistent with the belief that DDTC is a potent inhibitor of spontaneous and GHRH-induced GH secretion. The action of DDTC could be mediated by a reduction in GHRH due to reduced norepinephrine synthesis, by an increase in somatostatin release through a dopaminergic stimulus, or by a direct dopaminergic effect on somatotrophs.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Inhibition of Norepinephrine Synthesis on Spontaneous and Growth Hormone-Releasing Hormone-Induced GH Secretion in Cynomolgus Macaques: Evidence for Increased Hypothalamic Somatostatin Tone

et al. 1990

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“…For example, whole tissue content studies completed in both rats and guinea pigs have demonstrated that NE turnover in the arcuate significantly increases on the afternoon of proestrus [23, 24]. In addition, microinjection of NE into the medial basal hypothalamus of male baboons has been shown to initiate a significant elevation in serum levels of PRL [25]. Together, these studies suggest that the α 2 -receptor may have a role in modulating dopamine activity within the arcuate, and subsequently, circulating levels of PRL.…”

Section: Introductionmentioning

confidence: 99%

Infusion of Alpha-2-Adrenergic Agents into the Paraventricular and Arcuate Nuclei of the Hypothalamus in the Siberian Hamster: Opposing Effects on Basal Prolactin

Dodge¹,

Badura²

2002

Neuroendocrinology

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Although the α₂-adrenergic receptor subtype has been shown to have a significant influence on circulating levels of prolactin (PRL), its exact role remains unclear. A multitude of studies have demonstrated that blockade of the α₂-receptor can either elevate or decrease circulating levels of PRL. α₂-Receptor-mediated control of both stimulatory and inhibitory arms of the PRL regulatory system may explain this discrepancy. Activation of the α₂-receptor has been shown to inhibit the activity of its target cell, and therefore antagonism of the α₂-receptor within a stimulatory component (e.g., paraventricular nucleus (PVN) of the hypothalamus) would theoretically have the opposite effect that it would have within an inhibitory component (arcuate nucleus of the hypothalamus). Thus, the purpose of this study was to investigate the functional role of the α₂-adrenergic receptor in modulating circulating levels of PRL both at the level of the PVN and arcuate using reverse microdialysis of α₂-adrenergic agents coupled with serial blood sampling in the male Siberian hamster. Male hamsters were fitted with a jugular cannula for serial blood sampling, and an indwelling microdialysis probe for intrahypothalamic drug administration between 08:00 and 10:00 h. Blood samples were collected every hour for 5 h (12:00–17:00 h). During the third sampling period, atipamezole (α₂-antagonist) or medetomidine (α₂-agonist) at one of three doses were infused into the PVN or the arcuate to assess effects on basal PRL. At the level of the PVN, infusion of atipamezole initiated an increase in basal PRL in a dose-dependent fashion, whereas infusion of medetomidine induced a significant decline in basal PRL in a dose-dependent fashion. In the arcuate, only the highest dose of atipamezole had an effect on PRL, and this was in the opposite direction from that seen in the PVN. Infusion of medetomidine did not have a significant effect on basal PRL levels; however, a trend toward a significant elevation was observed for the highest dose. These results suggest that the α₂-receptor subtype may have opposite effects on circulating levels of PRL within the PVN and arcuate regions, and may explain why antagonism of the α₂-receptor has been shown to initiate both surges and declines in basal levels of PRL.

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“…* This work was presented in part at the Endocrine Society Annual Meeting, Atlanta, 1990. Norepinephrine (NE) is an important regulator of GH secretion in the brain (9,10). Exogenous administration of NE or other a-adrenergic agonists evokes GH secretion (11,12). Blockade of NE synthesis using the dopamine-/?-hydroxylase (DBH) inhibitor diethyldithiocarbamate (DDTC) (13,14) has been studied widely as a means of acutely suppressing GH secretion.…”

mentioning

confidence: 99%

Induction of reversible growth retardation and growth hormone deficiency by blockade of norepinephrine synthesis in the rat

Malozowski

Mamalaki²,

Pleti³

et al. 1993

Acta Endocrinologica

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Norepinephrine is a major regulator of the release of growth hormone. Diethyldithiocarbamate, a dopamine-\g=b\-hydroxylase inhibitor, reduces norepinephrine synthesis and acutely inhibits growth hormone (GH) secretion. To investigate the long-term effects of dopamine-\g=b\-hydroxylase blockade on growth, we administered diethyldithiocarbamate (0, 40, 100 or 400 mg/kg sc b.i.d.) to 21-day-old female rats for 10 days. Food intake, body weight, and tail length were measured twice a week. Plasma GH levels and hypothalamic dopamine and norepinephrine content were measured; messenger ribonucleic acids (mRNAs) for GH-releasing hormone and somatostatin were determined by quantitative in situ hybridization. Diethyldithiocarbamate administration decreased GH levels (p<0.05) and retarded growth in a dose-dependent manner (p<0.05), without altering food intake. Co-administration of GH partially reversed the growth retardation in diethyldithiocarbamate-treated animals (p<0.05). Diethyldithiocarbamate treatment also increased the hypothalamic dopamine/ norepinephrine ratio (1.13 vs 0.41 control, p<0.05). Local levels of GH-releasing hormone and somatostatin mRNA were not altered by treatment. After discontinuation of diethyldithiocarbamate, growth rates returned to normal or transiently even to supranormal values. Norepinephrine synthesis blockade with diethyldithiocarbamate provides a model for reversible growth retardation, in which GH levels are decreased in the absence of decreased GH-releasing hormone mRNA. These results support a role for norepinephrine in the regulation of normal growth. Saul Malozowski, Food and Drug Administration, 5600 Fishers Lane, HFD-510 Rockville, MD 20857, USA Growth hormone deficiency (GHD) is an important endocrine cause of short stature and can occur as a permanent or transient condition (1). After reversal of GHD or GH-resistant states, such as malnutrition, subjects resume normal growth velocity but the extent of accelerated "catch-up" growth varies.Three rodent models of GHD have been developed: hypophysectomy (2), neonatal administration of monosodium glutamate (MSG) (3-6) and the inbred dwarf mouse (7, 8). Hypophysectomy produces many other hormonal deficiencies besides GHD. Administration of toxic amino acids such as MSG results in abnormal behavior, such as tail self-mutilation; and there may be other hormonal abnormalities besides GHD. Colonies of inbred strains are difficult to obtain and to breed, and hormonal or metabolic alterations other than GHD also may cause growth retardation. All of these models have irreversible GHD. * This work was presented in part at the Endocrine Society Annual Meeting, Atlanta, 1990. Norepinephrine (NE) is an important regulator of GH secretion in the brain (9, 10). Exogenous administration of NE or other a-adrenergic agonists evokes GH secretion (11,12). Blockade of NE synthesis using the dopamine-/?-hydroxylase (DBH) inhibitor diethyldithiocarbamate (DDTC) (13, 14) has been studied widely as a means of acutely suppressing GH secretion. As DDTC ad...

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Noradrenergic and Dopaminergic Regulation of GH and Prolactin in Baboons

Cited by 15 publications

References 34 publications

Effects of Inhibition of Norepinephrine Synthesis on Spontaneous and Growth Hormone-Releasing Hormone-Induced GH Secretion in Cynomolgus Macaques: Evidence for Increased Hypothalamic Somatostatin Tone

Effects of Inhibition of Norepinephrine Synthesis on Spontaneous and Growth Hormone-Releasing Hormone-Induced GH Secretion in Cynomolgus Macaques: Evidence for Increased Hypothalamic Somatostatin Tone

Infusion of Alpha-2-Adrenergic Agents into the Paraventricular and Arcuate Nuclei of the Hypothalamus in the Siberian Hamster: Opposing Effects on Basal Prolactin

Induction of reversible growth retardation and growth hormone deficiency by blockade of norepinephrine synthesis in the rat

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