5-HT1 and 5-HT2 receptor agonists blunt +/- -alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-stimulated GH secretion in prepubertal male rats

Pinilla, Leonor; González, Laura; Tena‐Sempere, Manuel; Aguilar, E.

doi:10.1530/eje.0.1440535

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…Similar changes have been described for the GABAergic control of gonadotropin secretion (37,38). It is possible that the inhibitory effect on FSH release, observed only on day 16 of age, after activation of 5-HT 1A , 5-HT 2 and 5-HT 3 receptors is limited to specific periods of development, as is the case for the serotoninergic control of GH secretion (17).…”

Section: Discussionsupporting

confidence: 59%

“…One of the major findings of the present study is that, as is the case for GH release (17), the stimulatory effect of NMDA on LH secretion can be blocked by coactivation of the serotoninergic system, through specific 5-HT 1 and 5-HT 2 receptormediated pathways. In this sense it has been described (39) that the serotoninergic system via 5-HT 1 , but not 5-HT 2 , receptors inhibits LH release in ovariectomized rats primed with steroids.…”

Section: Discussionmentioning

confidence: 55%

“…For example, bicuculline (antagonist of GABA A receptors) and phaclofen (antagonist of GABA B receptors) blocked glutamic acid-evoked LHRH secretion by arcuate nucleus -median eminence preparations (15). Similarly, the stimulatory effect of muscimol (agonist of GABA A receptors) on LH secretion was blocked by MK-801 (antagonist of NMDA receptors) (16) Recently, we have described that activation of 5-HT 1 and 5-HT 2 serotoninergic receptors blunted the AMPAstimulated GH secretion in prepubertal male rats (17), and that NMDA receptors, but not AMPA receptors, are needed for the stimulatory effect of GABA on GH secretion (18). In the present experiments, we aimed to obtain information about (a) the role of different 5-hydroxytryptamine (5-HT) receptor subtypes in the control of gonadotropin secretion in different stages of prepubertal development and (b) the interactions between AMPA and NMDA with different serotoninergic receptors in the control of LH secretion.…”

Section: Introductionmentioning

confidence: 96%

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5-HT1 and 5-HT2 receptor activation reduces N-methyl-D-aspartate (NMDA)-stimulated LH secretion in prepubertal male and female rats

Pinilla

González²,

Tena‐Sempere³

et al. 2003

European Journal of Endocrinology

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Objective: Excitatory amino acids and serotonin are involved in the control of gonadotropin secretion. The actions of these neurotransmitters are interconnected and recently we have reported that 5-HT 1 and 5-HT 2 receptor agonists blunted (^)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-stimulated GH secretion in prepubertal rats. The present experiments were carried out to analyze the effects of activation of different 5-hydroxytryptamine (5-HT) receptor subtypes on gonadotropin secretion and their role in the N-methyl-D-aspartate (NMDA)-stimulated LH release. Design and methods: We analyzed the gonadotropin secretion after manipulation of serotoninergic and aminoacidergic systems and their interactions in 5-, 16-and 23-day-old male and female rats. To this end, serum LH and FSH concentrations were measured in rats treated with 5-hydroxytryptophan methyl ester (5-HTP) (a precursor of 5-HT synthesis) plus Fluoxetine (Fx, a blocker of 5-HT reuptake), D,L-p-chlorophenyl-alanine methyl ester (PCPA, a blocker of 5-HT synthesis), R-(+)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, an agonist of 5-HT 1A receptors), (^)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and a-methyl-5-hydroxytryptamine (a-Me-5-HT, agonists of 5-HT 2 receptors), and 1-Phenylbiguanide (1-PHE an agonist of 5-HT 3 receptors). In addition, the effects of 8-OH-DPAT and DOI on NMDA-stimulated LH secretion were analyzed. Results: Neither the activation nor blockade of the serotoninergic system modified LH secretion. Basal gonadotropin secretion remained unchanged in 23-day-old male and female rats after activation of 5-HT 1A , 5-HT 2 and 5-HT 3 receptors. The stimulatory effect of NMDA on LH secretion was blocked in both sexes after activation of the serotoninergic system, through specific 5-HT 1 and 5-HT 2 receptor agonists. Conclusions: Activation of serotoninergic receptors decreased the stimulatory effect of NMDA on LH secretion in prepubertal male and female rats.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 96%

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5-HT1 and 5-HT2 receptor activation reduces N-methyl-D-aspartate (NMDA)-stimulated LH secretion in prepubertal male and female rats

Pinilla

González²,

Tena‐Sempere³

et al. 2003

European Journal of Endocrinology

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“…Among potential interactions, assessment of the cross-talk between ghrelin and other pivotal signals in the control of GH secretion, such as EAAs, serotonin and nitric oxide (NO), is highly relevant for the complete elucidation of the mode of action of ghrelin in the regulation of GH release. EAAs are potent stimulatory inputs for GH secretion, acting through ionotropic NMDA, KA and AMPA receptors [14, 15, 16], whereas the serotoninergic system is able to modulate GH responses to different elicitors, such as AMPA receptor agonists [17]. Similarly, our previous evidence indicates a permissive role of endogenous NO in the releasing activity of different elicitors of GH secretion, including GHSs [18, 19]; yet the involvement of NO in ghrelin-induced GH secretion remains to be proven.…”

Section: Introductionmentioning

confidence: 99%

Role of Ghrelin in the Control of Growth Hormone Secretion in Prepubertal Rats: Interactions with Excitatory Amino Acids

et al. 2003

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Ghrelin is a 28-amino-acid peptide, with an essential n-octanoyl modification at Ser3, that elicits growth-hormone (GH) secretion in rats and humans. At present, the mechanisms of ghrelin action and its interactions with other systems controlling GH secretion remain poorly characterized. In this context, the present study was undertaken to obtain information about ontogeny and possible gender differences in the GH-releasing activity of ghrelin, and to delineate its primary site(s) of action at the hypothalamus and/or pituitary. In addition, the interactions between ghrelin and other relevant signals in the control of GH secretion, such as excitatory amino acids (EAAs), nitric oxide (NO) and serotonin, were assessed. Experiments were carried out in infantile-prepubertal animals, when GH pulsatility is not yet established. Systemic administration of ghrelin (25 nmol/rat, i.p.) to 5-, 10- and 23-day-old male and female rats increased plasma GH levels from day 10 onwards. This action was NO dependent, since it disappeared in 23-day-old males after pretreatment with an inhibitor of NO synthase (NAME). Similarly, central infusion of ghrelin (3 nmol/rat, i.c.v.) elicited GH responses in 10- and 23-day-old animals significantly higher than after systemic administration. By contrast, in vitro challenge of pituitary tissue with increasing doses of ghrelin (10^–9–10^–7M) failed to enhance GH release into the incubation medium, whereas stimulation with GH-releasing hormone (GHRH; 10^–7M) or GHRP-6 (10^–7M) was effective. Finally, effects of ghrelin were blocked by pretreatment with MK-801 and NBQX antagonists of EAA ionotropic receptors and after manipulation of endogenous serotoninergic tone. In addition, the potent releasing activity of EAA agonists NMDA and AMPA was blunted by pretreatment with D-Lys3-GHRP-6, a selective antagonist of the cognate ghrelin receptor, i.e. the GH-secretagogue receptor. In conclusion, our results demonstrate that GH-releasing activity of ghrelin appears early in the infantile period, is NO dependent and involves a primary hypothalamic site of action. The data also demonstrate for the first time the existence of a cross-talk between ghrelin and other neurotransmitter systems, such as EAAs and serotonin, in precise control of GH secretion.

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“…It is well established that GABA is one of several signaling molecules involved in the control of GH production [3, 7, 31, 32]. GABA-affecting hormone secretion by pituitary endocrine cells is produced in the hypothalamus [8, 9, 10, 11], but, as shown recently, also within the pituitary itself, namely in POMC and in GH cells [12].…”

Section: Discussionmentioning

confidence: 99%

An Autocrine Role for Pituitary GABA: Activation of GABA-B Receptors and Regulation of Growth Hormone Levels

et al. 2002

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There is increasing evidence suggesting that the neurotransmitter γ-aminobutyric acid (GABA) is a local factor involved in the regulation of endocrine organs. Examples of such functions are documented in the pancreas, but recent results suggest that GABA may act in a similar way in the pituitary, in which GABA receptors are expressed and pituitary growth hormone (GH) cells provide a source of GABA. We hypothesised that GABA secreted in somatotropes may act as an autoregulatory signaling molecule. To test this hypothesis we first examined the nature of GABA receptors expressed by GH cells. RT-PCR analysis demonstrated that GABA-B receptor subunits R1 and R2 are present in the whole rat pituitary. Laser microdissection of immunostained GH cells, followed by RT-PCR as well as immunoelectron microscopy, showed that GABA-B receptors are expressed on somatotropes. To investigate GABA-B receptor function in somatotropes, we used rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked by high performance liquid chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing cells, GABA acts as an autocrine factor via GABA-B receptors to control GH levels.

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5-HT1 and 5-HT2 receptor agonists blunt +/- -alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-stimulated GH secretion in prepubertal male rats

Cited by 7 publications

References 38 publications

5-HT1 and 5-HT2 receptor activation reduces N-methyl-D-aspartate (NMDA)-stimulated LH secretion in prepubertal male and female rats

5-HT1 and 5-HT2 receptor activation reduces N-methyl-D-aspartate (NMDA)-stimulated LH secretion in prepubertal male and female rats

Role of Ghrelin in the Control of Growth Hormone Secretion in Prepubertal Rats: Interactions with Excitatory Amino Acids

An Autocrine Role for Pituitary GABA: Activation of GABA-B Receptors and Regulation of Growth Hormone Levels

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