Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

Arce, V.; Lima, Luís; Lois, Noemi; Rodrı́guez, A. O.; Díaz, María Jesús Villamide; Tresguerres, Jesús A.F.; Devesa, Jesús

doi:10.1159/000125711

Cited by 20 publications

(11 citation statements)

References 29 publications

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“…Dopamine releases GHRH and SRIF from the hypothalamus, and the final GH response to dopamine is dependent on the endogenous DA tone (15). Induction of dopaminergic blockade in 10 normal human subjects increased GHRH-induced GH secretion and caused a loss of the relationship between pre-GHRH plasma GH values and GHRH-elicited GH peaks, suggesting that central DA may stimulate SRIF secretion (28). DA-induced SRIF release has also been observed in the rat (29).…”

Section: Discussionmentioning

confidence: 94%

Suppression of Rat and Human Growth Hormone and Prolactin Secretion by a Novel Somatostatin/Dopaminergic Chimeric Ligand

Ren

Kim²,

Taylor³

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

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As cotreatment of somatostatin (SRIF) and dopamine (DA) agonists reduces GH in acromegaly more effectively than either agonist alone, SRIF and DA receptors (SSTR and DAR) may interact with enhanced functional activity. The selective SSTR2 agonist, BIM-23023 (50% effective dose, 0.42), and the DAR2 agonist, BIM-53097 (50% effective dose, 22.1), dose- dependently inhibited GH secretion in cultured primary rat and human fetal as well as in human pituitary tumor cells derived from GH-secreting adenomas. The combination of individual SSTR2 and DAR2 agonists was additive for suppressing GH secretion in both rat and human pituitary cells. BIM-23A387 is a chimeric compound that contains structural elements of both SRIF and DA in a single molecule and retains potent, selective binding to DAR2 and SSTR2. BIM-23A387 (50% effective dose, 0.16 for SSTR2 and 24.5 for DAR2), displayed similar efficacy in suppressing GH secretion from rat pituitary cells as the combination of the two individual agonists. In contrast, the chimeric molecule was more potent than individual selective analogs in suppressing GH secretion by human fetal pituitary and GH-secreting adenoma cells (P < 0.05). Although the DAR2 antagonist, sulpiride, reversed BIM-23A387-induced GH suppression, blockade of SSTR2 by the selective SSTR antagonist, BIM-23454, did not block BIM-23A387-suppressed GH secretion. These results indicate that mechanisms by which the chimeric molecule suppresses pituitary GH secretion may not be mediated by individual SSTR2 or DAR2 signaling, respectively. Functional interaction of the two receptors may explain the clinical observation that more effective GH suppression is achieved when DAR2 and SSTR2 agonists are administered in combination. The SRIF/DA chimeric molecule, BIM-23A387, represents a novel tool for effective drug treatment of acromegaly and for prolactinomas otherwise resistant to dopaminergic therapy.

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Section: Discussionmentioning

confidence: 94%

Suppression of Rat and Human Growth Hormone and Prolactin Secretion by a Novel Somatostatin/Dopaminergic Chimeric Ligand

Ren

Kim²,

Taylor³

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…GH secretion in the pituitary is mainly regulated by GHRH and somatostatin, both of which are derived from the neurosecretory nuclei of the hypothalamus and are controlled by dopamine (Tannenbaum and Ling 1984;Arce et al 1991;Müller et al 1999). García-Tornadú et al (2006) showed that a loss of dopamine signaling via the hypothalamic D2R caused the reduced release of GHRH from hypophysiotropic neurons in D2R knockout mice, suggesting that hypothalamic D2R plays an important role in GHRH secretion.…”

Section: Discussionmentioning

confidence: 99%

“…Arce et al (1991) showed that blockade of the central dopaminergic pathway by metoclopramide in 10 normal human subjects increased GHRH-induced GH secretion, possibly by inhibiting the hypothalamic release of somatostatin. The modest increase in serum GH by metoclopramide in the present case may be caused by the blockade of the central dopaminergic pathway as well as its antagonistic action on D2R in the pitu- itary adenoma.…”

Section: Discussionmentioning

confidence: 99%

Bromocriptine, a Dopamine Agonist, Increases Growth Hormone Secretion in a Patient with Acromegaly

Arihara

Sakurai

Yamashita

et al. 2014

Tohoku J. Exp. Med.

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Bromocriptine, a potent D2-dopamine agonist, suppresses growth hormone (GH) secretion in most patients with acromegaly and has been approved for the treatment of acromegaly. Here we report a patient with acromegaly who showed increased GH secretion after administration of bromocriptine. A 70-year-old man with acromegalic manifestation was admitted to our hospital because of a pituitary tumor invading to the right cavernous sinus detected by brain magnetic resonance imaging. Serum GH and insulin-like growth factor-I (IGF-I) levels were elevated in several occasions (GH: 15.0-51.7 ng/mL, reference range: < 2.47 ng/mL; and IGF-I: 776-856 ng/mL, reference range: 57-175 ng/mL). Effect of bromocriptine on serum GH levels was then studied because pre-operative treatment with a D2-dopamine agonist was planned in order to reduce the tumor size and serum GH levels before surgery. After oral administration of 2.5 mg of bromocriptine, serum GH levels were unexpectedly increased from 30.7 ng/mL to 189 ng/mL, despite the fact that the levels of prolactin (PRL) were decreased from 4.2 ng/mL to 0.6 ng/mL. By contrast, serum GH levels were decreased by a somatostatin analogue, octreotide. Transsphenoidal surgery of the pituitary tumor was performed after treatment of octreotide. Histological analysis and immunohistochemistry revealed a GH-producing pituitary adenoma positive for D2-dopamine receptor. This case of acromegaly suggests that the preliminary test with a single administration of a short-acting D2-dopamine agonist, bromocriptine, is mandatory before the long-term therapy with a D2-dopamine agonist in patients with GH-secreting pituitary tumors.

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“…Dopamine also inhibits GH secretion from cultured pituitary cells, i.e. at the pituitary level (37,38). In contrast, the systemic administration of dopamine results in GH increment (27), probably due to the activation of hypothalamic hormones stimulating GH release.…”

Section: Journal Of Endocrinology (1999) 140mentioning

confidence: 99%

Paradoxical GH response to TRH during status epilepticus in man

Lindbom¹,

Al²,

Tomson³

1999

European Journal of Endocrinology

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Information on GH in relation to epilepsy is sparse, and to our knowledge there is no information on GH levels during status epilepticus in man. We studied GH in serum in six patients during status epilepticus, and in a control group of six seizure-free patients with epilepsy, before and after injection of TRH. The baseline GH values before TRH administration were within the normal range in all patients. After injection of TRH all patients with status epilepticus showed a paradoxical peak-shaped increase of GH to at least twice their baseline levels within 45 min after the injection (median basal GH value 1.5 mU/l and median peak GH value 6.5 mU/l, mean increase 330%). No uniform reaction to TRH was observed in the control group (median basal GH value 2.7 mU/l and median of the highest value within 45 min 5.2 mU/l). A paradoxical peak reaction of GH to TRH was significantly more frequent in the status epilepticus group compared with the control group (P = 0.008, Fisher exact probability test). TRH is not considered a GH-releasing hormone in humans during normal conditions, but a paradoxical response of GH to TRH, similar to that observed during status epilepticus, has been reported in various other pathological conditions, such as acromegaly, liver cirrhosis, mental depression and hypothyroidism. Our results of GH release after TRH administration in patients with status epilepticus suggest an altered regulation of GH as a result of the long-standing epileptic activity.

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Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

Cited by 20 publications

References 29 publications

Suppression of Rat and Human Growth Hormone and Prolactin Secretion by a Novel Somatostatin/Dopaminergic Chimeric Ligand

Suppression of Rat and Human Growth Hormone and Prolactin Secretion by a Novel Somatostatin/Dopaminergic Chimeric Ligand

Bromocriptine, a Dopamine Agonist, Increases Growth Hormone Secretion in a Patient with Acromegaly

Paradoxical GH response to TRH during status epilepticus in man

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