Gonadal and Age-Related Influences on NMDA-Induced Growth Hormone Secretion in Male Rats

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

doi:10.1159/000054398

Cited by 13 publications

(12 citation statements)

References 24 publications

(44 reference statements)

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“…The fast neurotransmitters GABA and glutamate were implicated previously in controlling GH secretion (Giustina and Veldhuis, 1998;Gonzalez et al, 1999;Müller et al, 1999;Pinilla et al, 1999), and we can now confirm that they regulate GHRH neurons directly, in a monosynaptic manner. Furthermore, disabling action potential propagation with TTX blunted of the effects of these neurotransmitters on GHRH neurons in vitro.…”

Section: Intrinsic Properties Of Ghrh-gfp Neuronssupporting

confidence: 78%

“…Furthermore, GABAergic and glutamatergic inputs to the GHRH system, implicated indirectly from effects on GH release, have not yet been studied directly at the hypothalamic GHRH level (Giustina and Veldhuis, 1998;Gonzalez et al, 1999;Müller et al, 1999;Pinilla et al, 1999). How these transmitters regulate GHRH neurons is of considerable interest, because data related to feeding circuits showed that GABAergic and glutamatergic neurons play a central role in the organization of arcuate nucleus activity (Horvath and Diano, 2004;Sternson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Dual-Level Afferent Control of Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRH–Green Fluorescent Protein Transgenic Mice

Baccam¹,

Alonso²,

Costecalde³

et al. 2007

J. Neurosci.

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The organization of the peptidergic neurons of the hypothalamic arcuate nucleus is not fully understood. These include growth hormonereleasing hormone (GHRH) neurons involved in growth and metabolism. We studied identified GHRH neurons of GHRH-green fluorescent protein transgenic mice using patch-clamp methods and focused on gender differences, which govern the physiological patterns of GHRH release. Both the spontaneous firing rates and the intrinsic properties of GHRH neurons were similar in males and females, although higher glutamatergic currents were noticed in females. Surprisingly, marked gender differences in GHRH neuronal activity were observed in response to the muscarinic agonist carbachol (CCh). In females, CCh enhanced action potential firing in all GHRH neurons. In males, CCh enhanced action potential firing in two-thirds of GHRH neurons, whereas it decreased firing in the remainders. M 1 agonist McN-A343 (10 M) mimicked, and M 1 antagonist pirenzepine (3 M) blocked the effects of CCh. In both genders, CCh did not change the intrinsic properties of GHRH neurons, although it strongly increased the frequency of glutamatergic currents, in the presence or absence of tetrodotoxin. In males only, CCh enhanced the frequency of GABAergic currents, and this modulation was antagonized by tetrodotoxin. Thus, the muscarinic regulation involved differential control of afferent inputs at short and long distances in male and female mice. The dual-level control could be a mechanism whereby the selective modulation of the GHRH system (short-distance control) is adjusted to the integrated regulation of arcuate nucleus activity (long-distance control).

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Section: Intrinsic Properties Of Ghrh-gfp Neuronssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Dual-Level Afferent Control of Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRH–Green Fluorescent Protein Transgenic Mice

Baccam¹,

Alonso²,

Costecalde³

et al. 2007

J. Neurosci.

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“…In neonatal rats, GH secretion is stimulated by γ-aminobutyric acid (GABA) [3], thyrotropin-releasing hormone (TRH) [4, 5], growth-hormone-releasing hormone (GHRH) [6]and excitatory amino acids (EAAs) [7]. The stimulatory effect of EAAs is mediated by activation of N-methyl- D -aspartate (NMDA), kainate and (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors [8, 9, 10]. …”

Section: Introductionmentioning

confidence: 99%

“…To carry out the proposed analysis, 5-day-old rats were used, a model selected on the basis of previous reports showing the ability of GABA, NMDA, and AMPA to stimulate GH secretion during the neonatal period, in particular at that age [3, 8, 10]. …”

Section: Introductionmentioning

confidence: 99%

Cross-Talk between Excitatory and Inhibitory Amino Acids in the Regulation of Growth Hormone Secretion in Neonatal Rats

Pinilla

González²,

Tena‐Sempere³

et al. 2001

Neuroendocrinology

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Experiments were carried out in 5-day-old male and female rats in order to assess the respective roles of distinct γ-aminobutyric acid (GABA) receptor subtypes in the control of growth hormone (GH) secretion in the newborn rat and to identify the potential sexual dimorphism of GABA actions on GH release. The interplay of GABA and excitatory acids (EAAs) to control GH secretion was also analysed. Effects of specific GABA_A, GABA_B and GABA_C agonists upon GH secretion as well as of co-administration of GABA and agonists and antagonists of EAA receptors were monitored in 5-day-old male rats. The data confirm that GABA stimulates GH secretion in 5-day-old rats, but indicate that the effect is sexually dimorphic, being greater in females. Stimulation of GH secretion by GABA is mainly mediated by GABA_A receptors, while GABA_C appears to be ineffective. Stimulatory effects of GH by GABA and muscimol, a GABA_A receptor agonist, are blocked by pretreatment with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclophepten-5-10-imine hydrogen maleate (MK-801), an antagonist of N-methyl-D-aspartate (NMDA) receptors, but not by 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]-quinoxaline-7-sulfonamide (NBQX), an antagonist of (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Simultaneous administration of GABA and NMDA was additive on GH release while basal GH secretion was not affected by either bicuculline or the respective blockers of GABA_A and GABA_B receptors. In conclusion, our results suggest that cross-talk between inhibitory (GABA) and EAAs is involved in the control of GH secretion in neonates.

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“…Thereafter, the drugs were dissolved in saline up to the working concentration. The doses and route of administration of different drugs as well as the time-points for hormone measurements were selected based on the previously reported effectiveness (Negro-Vilar et al 1979, Martin et al 1995, Pinilla et al 1998, Gonzalez et al 1999a and the absence of behavioural changes. In addition, to analyse the effectiveness of AMPA to change PRL secretion after blockade of different receptor subtypes as well and in hyper-and hypo-prolactinaemic situations, NBQX, MK-801, -MPT, DDC, 5-HTP and fluoxetine were injected prior to AMPA administration.…”

Section: Animals and Drugsmentioning

confidence: 99%

Regulation of prolactin secretion by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in male rats

Gonzalez

Pinilla²,

Tena‐Sempere

et al. 2000

Journal of Endocrinology

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The secretion of PRL is controlled by different hypothalamic signals. Depending on the experimental model, PRL secretion increases or decreases after activation of N-methyl--aspartic acid and kainate receptors. Recently we have described that activation of -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors inhibits PRL secretion in prepubertal male rats. The aim of present study was to examine (1) the physiological relevance of this finding, (2) the possible age-related changes observed after activation or blockade of AMPA receptors, (3) the specificity of the AMPA effect, (4) the hypothalamic and/or pituitary localization of AMPA action, and (5) the mechanism(s) of action of AMPA agonists.In a first set of experiments, neonatal males (5 and 10 days old) and prepubertal (23 days old) male rats were injected with AMPA (1, 2·5 or 5 mg/kg) or the antagonist of AMPA receptors 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo (f) quinoxaline-7-sulfonamide (NBQX; 0·25 or 0·50 mg/kg). Serum PRL concentrations decreased significantly 15 and 30 min after i.p. administration of AMPA in prepubertal male rats, while the inhibitory effect of AMPA was not observed in 5-and 10-day-old males. The effect of AMPA was abolished by NBQX but not by MK-801 (a selective antagonist of NMDA receptors). NBQX alone (0·25 or 0·50 mg/kg) had no effect on PRL release. In vitro, AMPA slightly stimulated PRL secretion by hemipituitaries from prepubertal males, suggesting that the hypothalamus is likely the site of action for the reported inhibitory action of AMPA on PRL release. In this sense, the blockade of AMPA effects in animals pretreated with domperidone (a dopaminergic antagonist) or -methyl-p-tyrosine (an inhibitor of dopamine synthesis) suggests that an increase in the release of hypothalamic dopamine is probably the mechanism involved in the effect of AMPA. In a second set of experiments, the effects of AMPA (2·5 mg/kg i.p.) and NBQX (0·5 mg/kg i.p. and 20 or 40 nmol i.c.v.) were tested in freely moving adult male rats sampled during periods of 2, 3 or 6 h. In contrast with data obtained in prepubertal rats, neither AMPA nor NBQX affected PRL secretion.In conclusion, these data indicate that activation of AMPA receptors inhibits PRL secretion in prepubertal male rats. This effect probably involves the release of dopamine from the hypothalamus and disappears in adulthood.

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Gonadal and Age-Related Influences on NMDA-Induced Growth Hormone Secretion in Male Rats

Cited by 13 publications

References 24 publications

Dual-Level Afferent Control of Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRH–Green Fluorescent Protein Transgenic Mice

Dual-Level Afferent Control of Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRH–Green Fluorescent Protein Transgenic Mice

Cross-Talk between Excitatory and Inhibitory Amino Acids in the Regulation of Growth Hormone Secretion in Neonatal Rats

Regulation of prolactin secretion by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in male rats

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