Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion in prepubertal male rats

Aguilar, E.; Tena‐Sempere, Manuel; Aguilar, Rafaela; Gonzalez, D; Pinilla, Leonor

doi:10.1530/eje.0.1370099

Cited by 18 publications

(19 citation statements)

References 34 publications

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“…In vivo it has been reported that NO is essential to elicit the ovulatory PRL surges in female rats [18], and NAME administration inhibits the PRL secretion in prepubertal females [24]. The present experiments indicate that NAME administration did not change the pulsatile PRL secretion in adult male rats which agrees with previous experiments from our group, showing that male rats of different ages failed to respond after NAME administration [25, 26]. Taken together, the results obtained for LH and PRL in males and females suggest a possible dimorphic role of NO in the control of the pituitary function.…”

Section: Discussionsupporting

confidence: 91%

Effects of Systemic Blockade of Nitric Oxide Synthases on Pulsatile LH, Prolactin, and GH Secretion in Adult Male Rats

et al. 2001

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Background: Nitric oxide (NO) has emerged as an important neurotransmitter involved in the control of the neuroendocrine function. NO acts at hypothalamic, pituitary, and gonadal levels. Previous data from our laboratory showed that blockade of NO generation, after systemic administration of a NO synthase inhibitor (Nω-nitro-arginine methyl ester, NAME), increased the luteinizing hormone (LH) secretion in intact and ovariectomized females, whereas a blockade of spontaneous and steroid-induced LH and prolactin surges after NO synthase inhibition has been also described. Methods and Results: Adult male rats were implanted with chronic intra-auricular cannulae and 5 days later sampled at 15-min intervals during 6 h (10.00–16.00 h). Administration of NAME (40 mg/kg at 08.00 and 13.00 h) stimulated significantly (p ≤ 0.01) the LH secretion, increasing LH pulse amplitude (0.58 ± 0.14 vs. 0.08 ± 0.01 ng/ml in controls), mean LH levels (0.64 ± 0.15 vs. 0.15 ± 0.03 ng/ml in controls), and area under curve (239 ± 56 vs. 57 ± 13 in controls). This effect was blocked by coadministration of sodium nitroprusside (SNP), a NO donor (0.5 mg/kg). The action of NAME was observed 3 h after administration, in contrast to the earlier response detected in female rats, and it appeared selective for LH, as prolactin and growth hormone secretion remained unchanged. Further analysis was carried out to determine whether the effect of NAME on the LH secretion was indirect and mediated by changes in testosterone release. To this end, adult male rats were decapitated 2 h after administration of NAME (40 mg/kg), SNP (0.5 mg/kg), or L-nitro-arginine methyl ester (L-AME), a substrate for NOS (1 g/kg). The serum testosterone concentrations were unchanged after NAME administration, but inhibited by SNP and L-AME. Finally, the effect of NAME and SNP on in vitro testosterone secretion was analyzed. NAME (10 mM) did not affect basal testosterone production, but inhibited the human chorionic gonadotropin stimulated testosterone secretion. Conclusions: These data strongly suggest that the stimulatory effect of NAME on LH secretion is not due to an inhibition of testosterone release and is exerted at the hypothalamic-pituitary level.

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Section: Discussionsupporting

confidence: 91%

Effects of Systemic Blockade of Nitric Oxide Synthases on Pulsatile LH, Prolactin, and GH Secretion in Adult Male Rats

et al. 2001

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“…The effect of NMDA on PRL secretion is agedependent, as NMDA inhibited prolactin release in prepubertal rats (9,26), probably through an increase in dopamine release, as concentrations of dopamine were increased in the pituitary and decreased in the hypothalamus after NMDA treatment. Differences in the effects of NMDA on PRL secretion in prepubertal and adult females are likely to be related to their different effects on tuberoinfundibular dopamine activity, as suggested by the different effects of NMDA on pituitary dopamine concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…At the hypothalamic level, a dual role through the stimulation/inhibition of the secretion of dopamine and PRL releasing factors (PRFs) has been proposed (10,11,13,25,26). At the pituitary level, NMDA and kainic acid inhibited PRL release (13,26).…”

Section: Discussionmentioning

confidence: 99%

Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in hyper- and hypoprolactinaemic conditions

Pinilla

Tena‐Sempere

Aguilar

et al. 1998

European Journal of Endocrinology

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Objective: The stimulatory and inhibitory effects of N-methyl-D-aspartic acid (NMDA) and kainic acid on prolactin (PRL) secretion have been correlated with the serum prolactin concentrations before drug administration. In the present experiments, we analysed the role of NMDA and kainic acid in PRL secretion in females with different serum concentrations of PRL. Methods: Hypoprolactinaemic females were obtained by ovariectomy or after administration of diethyldithiocarbamate (an inhibitor of dopamine-b-hydroxylase). Chronic hyperprolactinaemia was induced by neonatal administration of testosterone or oestradiol and acute hyperprolactinaemia was induced either by administration of a-methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) or by ether exposure. To analyse the role of dopamine in the effects of NMDA, we measured pituitary concentrations of dopamine after NMDA treatment and the effects of pretreatment with domperidone. Results: (1) NMDA, but not kainic acid, stimulated PRL release in cyclic females. This effect was independent of serum PRL concentrations and was not accompanied by a decrease in pituitary concentrations of dopamine. (2) NMDA did not change PRL secretion in neonatally androgenized females, whereas NMDA and kainic acid inhibited PRL release in neonatally oestrogenized females. The inhibitory effects of NMDA and kainic acid were blocked by domperidone. (3) Kainic acid inhibited PRL secretion in prepubertal hyper-and hypoprolactinaemic rats. (4) Hyperprolactinaemia induced by ether stress was counteracted by administration of NMDA and kainic acid. Conclusions: (a) NMDA has a dual effect on prolactin secretion that is independent of prior prolactin concentrations and of dopamine activity, but kainic acid is only inhibitory. (b) The stimulatory or inhibitory effects of NMDA and kainic acid on PRL secretion were not strictly related to basal PRL concentrations and necessarily involved a change in the secretion of prolactin releasing factors, as no correlations were observed between changes in pituitary concentrations of dopamine and serum PRL concentrations. (c) Females rendered hyperprolactinaemic by neonatal administration of testosterone or oestradiol responded differently after NMDA administration. (d) NMDA and kainic acid blocked the mechanisms involved in stress-induced PRL secretion.

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“…Experiment 6: We have previously described that in prepubertal rats, activation of NMDA, KA or AMPA receptors decreases PRL secretion [21, 22, 23, 24, 25, 26, 27, 32]. To analyze the possible interactions between the inhibitory effects of EAAs (through NMDA and AMPA receptors) and ghrelin on PRL secretion, 23-day-old male rats were i.p.…”

Section: Methodsmentioning

confidence: 99%

“…Likewise, excitatory amino acids (EAAs), acting through ionotropic NMDA, KA and AMPA receptors, inhibit PRL release in prepubertal rats [21, 22, 23, 24, 25, 26, 27]. In contrast, serotonin (5-HT), vasoactive intestinal peptide, thyrotropin-releasing hormone and other neuropeptides increase PRL release [23, 27, 28, 29, 30]. To date, the contribution of ghrelin to the hypothalamic pathways controlling PRL secretion in rats remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Inhibits Prolactin Secretion in Prepubertal Rats

et al. 2004

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Ghrelin, a novel 28-amino-acid peptide primarily expressed in stomach and hypothalamus, has recently emerged as the endogenous ligand for the GH-secretagogue receptor with ability to stimulate GH secretion in humans and rats. In addition, ghrelin also stimulates prolactin (PRL) secretion in humans. However, its role in the regulation of PRL secretion in rats remains largely unknown. In this context, the present experiments were carried out to analyze the effects of ghrelin on PRL secretion in male and female rats. In detail, the ontogeny and potential sexual dimorphism in the PRL response to ghrelin was evaluated. In addition, the hypothalamic and/or pituitary site of primary action of ghrelin, as well as the possible interactions between ghrelin and other neurotransmitters, as nitric oxide, dopamine, serotonin or excitatory amino acids, in the precise control of PRL secretion were assessed. Experiments were conducted in prepubertal male and female animals. Systemic (i.p.) and central (i.c.v.) administration of ghrelin significantly inhibited PRL secretion. Such an inhibitory effect became evident after day 10 of age, was similar in males and females, and was also observed in hyperprolactinemic aged female rats. In contrast, however, challenge of pituitary samples in vitro with increasing doses of ghrelin (10^–9–10^–7M) failed to inhibit PRL secretion. Analysis of interactions between ghrelin and other systems involved in the control of PRL secretion revealed that neither blockade of dopaminergic receptors with domperidone, nor enhancement of serotoninergic tone with fluoxetine + 5-hydroxytryptophan altered the inhibitory response to ghrelin in terms of PRL secretion. Similarly, blockade of nitric oxide synthases with L-nitro-arginine-methyl ester failed to modify the magnitude of ghrelin-induced inhibition of PRL secretion, whereas ghrelin was unable to further decrease serum PRL levels after activation of ionotropic excitatory amino acid receptors by administration of NMDA or AMPA. In conclusion, our data indicate that ghrelin is able to inhibit PRL secretion in male and female rats, likely through an extrapituitary primary site of action that is independent of nitric oxide, dopamine, and serotonin systems.

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Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion in prepubertal male rats

Cited by 18 publications

References 34 publications

Effects of Systemic Blockade of Nitric Oxide Synthases on Pulsatile LH, Prolactin, and GH Secretion in Adult Male Rats

Effects of Systemic Blockade of Nitric Oxide Synthases on Pulsatile LH, Prolactin, and GH Secretion in Adult Male Rats

Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in hyper- and hypoprolactinaemic conditions

Ghrelin Inhibits Prolactin Secretion in Prepubertal Rats

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