Biomedical subjects

J A Moguilevsky

Publications and source records attributed to J A Moguilevsky.

At least 19 recordsLinked to original sources

PubMed2005

Leptin stimulates the reproductive male axis in rats during sexual maturation by acting on hypothalamic excitatory amino acids.

The purpose of the present study was to determine the effect of treatment with leptin on gonadotrophin secretion and hypothalamic GnRH, excitatory and inhibitory amino acids release, in prepubertal (15 days old) and peripubertal (30 days old) male rats. Rats of both ages received a single (ip) injection of 30 microg/kg leptin 60 minutes previous to sacrifice. Serum LH was determined, and the hypothalamus dissected and incubated in Earle's medium. GnRH and amino acids release were determined in the media. LH and GnRH were measured by RIA. Amino acids were assessed by HPLC-UV detection. In the two prepubertal stages, (prepubertal and peripubertal, 15 and 30 days of age respectively) leptin increased plasmatic LH levels (p < 0.01) and hypothalamic GnRH release (p < 0.01). Glutamate (GLU) release showed an increment in leptin-treated rats (p < 0.01) at both ages, while only the 30 days old rats showed an increment of the aspartate (ASP) release. GABA secretion was not modified by leptin treatment. In conclusion, the results demonstrated that leptin stimulates the LH-GnRH axis during sexual development in male rats, increasing the secretion of both hormones. The hypothalamic excitatory amino acid neurotransmitter system appears to be involved in this change.

Amino Acids↗

PubMed2003

Effect of leptin on hypothalamic release of GnRH and neurotransmitter amino acids during sexual maturation in female rats.

The purpose of the present study was to analyse the effect of leptin treatment on the hypothalamic release of GnRH, GABA, and the excitatory amino acids (EAA), aspartate (ASP) and glutamate (GLU) involved in NMDA neurotransmission in prepubertal (15 day old) and peripubertal (30 day old) female rats. The animals were treated with a single dose of leptin (30 microg/kg i.p.) and sacrificed 60 min later. Hypothalamic samples were incubated in Earle's medium; GnRH was determined by RIA and GLU, ASP and GABA by HPLC by UV detection. The hypothalamic release of GnRH was increased by leptin at both ages, the release being significantly higher in peripubertal than in prepubertal rats. The levels of hypothalamic GABA release were different in the two groups; whereas in prepubertal rats the hypothalamic release of GABA increased with leptin administration, the neurotransmitter release decreased in the peripubertal group. On the other hand, the release of ASP was modified only in the peripubertal group, where leptin significantly increased its hypothalamic release. No modifications in leptin-induced hypothalamic release of GLU were observed at the two ages studied. In conclusion, the results showed that leptin increased GnRH release by the hypothalamus of prepubertal and peripubertal rats. In peripubertal rats this increase was accompanied by a significant decrease in the hypothalamic release of GABA as well as an enhanced release of ASP. These results and previous reports suggest that at this stage of sexual maturation, leptin exerts an stimulatory effect on GnRH by inducing release of excitatory amino acids (ASP) and reducing release of inhibitory amino acids (GABA) involved in GnRH control. In prepubertal rats the stimulating effect of the adipocyte hormone on GnRH appears to be related to its stimulative action on GABA which at this age increases GnRH release.

Amino Acids↗

PubMed2001

Changes in the control of gonadotrophin secretion by neurotransmitters during sexual development in rats.

Gonadotrophin hormone releasing hormone (GnRH) is the primary messenger involved in sexual maturation and the onset of puberty. The activity of these neurons are controlled by several neurotransmitters systems. The onset of puberty implies changes from a prepubertal type of gonadotrophin secretion, characterized by a low activity of GnRH neurons, to an adult pattern of secretion with phasic and synchronous activation of GnRH neurons resulting in an increase in the amplitute and frequency of GnRH pulses. Neurotransmitter systems are involved in these changes of GnRH secretion during the onset of puberty by quantitative and qualitative modifications in the effect on GnRH secretion. Serotonin (5-HT), GABA and catecholamines (CA) have qualitative differences in the effects on GnRH and LH secretion in early prepubertal than in late prepubertal and adult female rats. The administration of 5-hydroxytryptophan a precursor of serotonin (5-HT) which increases 5-HT hypothalamic levels induces GnRH and LH release in early prepubertal female rats, these effects dissapear in late prepubertal stage having an inhibitory action in adult female rats. GABAergic system also stimulates GnRH and LH secretion in early prepubertal female rats and has an inhibitory action on this axis in late prepubertal period and in adult female rats. On the contrary the inhibition of catecholamines synthesis by alpha-methyl-p-tyrosine induced an increase of LH secretion in early prepubertal female rats and inhibitory effect in late prepubertal and adult stage. These effects indicate tha CA has an inhibitory effects on GnRH-LH secretion in early prepubertal female rats changing to an stimulatory action in the late puberty and adult rats. These qualitative modifications were observed only in female rats and are probably connected with the hypothalamic differentiation into a female type of gonadotrophin control. Opiadergic and excitatory amino acid systems have quantitative differences on GnRH-LH secretion during prepubertal and peripubertal and adult stages. Opiates has an high inhibitory tone in early prepubertal rats that is decreasing during sexual maturation to reach puberty. On the contrary EAA increases its stimulatory activity on GnRH-LH secretion during sexual maturation by increasing the hypothalamic release of aspartate and glutamate, the excitatory amino acids involved in GnRH release, and the sensibility of NMDA receptors to these amino acids. In conclusion sexual maturation and the onset of puberty in the female rats involve qualitative and quantitative modifications in the effects of neurotrasmitters system on GnRH secretion.

Animals↗

PubMed2001

Changes in the sensitivity of gonadotrophin axis to leptin during sexual maturation in female rats.

OBJECTIVES: The aim of the present paper was to determine the sensitivity of the GnRH-LH axis to leptin administration during sexual maturation in female rats. METHODS: For this purpose the hypothalamic concentration of GnRH, the pituitary content and the plasmatic levels of LH were determined in prepubertal (15 days of age) and peripubertal female rats (30 days of age), treated with leptin at a dose of 30 microg/kg. i.p. in a single injection, 90 min before sacrifice. RESULTS: The results indicate that leptin significantly increased the GnRH concentration at 15 days of age (p <0.01). At 30 days of age the hormone did not significantly modify the hypothalamic GnRH content. Leptin increased the pituitary LH levels, both in prepubertal and peripubertal rats. Nevertheless, while the increase at 15 days of age was around 180%, in peripubertal rats it was about 51,2 %. In spite that leptin significantly increased LH plasmatic levels at both ages (p < 0.01 ), in rats of 15 days of age leptin increased LH in about 244%, at 30 days of age this increase was only about 102%. CONCLUSION: These results clearly demonstrated that leptin has stimulatory effect on gonadotrophin axis been higher in prepubertal than in peripubertal rats. On these basis, and on the results of previous papers, (in which it has been demonstrated that the hypothalamic control of gonadotrophins by neurotransmitters and neuromodulators also showed qualitative and quantitative changes during sexual maturation), it is proposed that these differences are connected with the maturation of the neuroendocrine mechanisms involved in the regulatory action of leptin on the gonadotrophins axis.

Animals↗

PubMed2000

Age-related differences in the effects of bacterial endotoxin (LPS) upon the release of LHRH, gonadotropins and hypothalamic inhibitory amino acid neurotransmitters measured in tissues explanted from intact male rats.

In adult rats, bacterial endotoxin (lipopolysaccharide or LPS) is known to diminish the activity of the reproductive axis, mainly by inhibiting luteinizing hormone-releasing hormone (LHRH) secretion; until now, this effect has not been studied in immature rats. The aim of the present study was to evaluate the effect of LPS 1) on LHRH output (and associated changes in the release of inhibitory amino acid neurotransmitters such as gamma-aminobutyric acid (GABA) and taurine) by superfused hypothalamic fragments, and 2) on gonadotropin secretion by incubated hemipituitaries, obtained from young adult (60-day-old) and peripubertal (30-day-old) intact male rats. In adult animals, LPS induced a significant inhibition (50% of basal values) of LHRH release, accompanied by an increase in GABA and taurine output. In juvenile rats the inhibition of LHRH secretion by LPS attained 90% of basal values (p<0.0001 versus adult rats), and the concurrent increase in GABA release was significantly greater (p<0.0001 versus adult rats). LPS did not affect in vitro gonadotropin secretion in adult animals. Conversely, the release of these hormones was significantly (p<0.001 and <0.02 for LH and FSH, respectively) reduced in 30-day-old rats. Our results demonstrate the existence of age-related differences in the effect of LPS on LHRH and gonadotropin secretion. These differences might well be attributed to an increased activity of the hypothalamic GABAergic system. Furthermore, the participation of other factors known to play a role in immune-neuroendocrine relationships (e.g., corticotropin-releasing hormone, testosterone) is discussed.

Aging↗

PubMed2000

Interrelationships of GABAergic, serotoninergic and excitatory amino acid systems in its regulatory effect on prolactin secretion in prepubertal rats.

GABAergic, serotoninergic and excitatory amino acid systems (EAAs) regulate the prolactin (PROL) secretion in prepubertal female rats. The aim of the present paper was to determine the interrelationships of these systems on the control of this pituitary hormone. It was carried out through the following scheme: 1. The participation of the EAAs and serotonin in the effect of GABAergic system on PROL release, determined by evaluating the GABA A and GABA B receptor agonists. It was carried out on animals that were previously treated with AAEs receptor antagonist or p-chlorophenylamphetamine (PCA), this one depleting serotonin in the hypothalamus. 2. The participation of GABAergic system in the effect of serotonin and EAAs systems, determined by the evaluation of the effects of EAAs receptor agonists and of 5-HTP, a serotonin precursor. With this purpose the rats were previously treated with GABA A and GABA B receptor antagonists. 3. The interrelationships between the EAAs and the serotoninergic systems in the control of PROL secretion, determined (a) by using EAAs agonists (in rats depleted of serotonin by PCA) and (b) using EAAs antagonists (in rats treated with 5-HTP, a serotonin precursor). The administration of GABAergic agonists significantly increased PROL secretion in prepubertal female rats. Neither EAAs antagonists nor the depletion of serotonin in the brain, modified the stimulatory effects of the GABAergic system on PROL levels. This is a clear indication that the activity of the GABAergic system is independent of the serotoninergic and of the EAAs system effects on the pituitary hormone. The EAAs neurotransmitter system agonists significantly increase PROL levels. This effect was blocked by the GABAergic system antagonists but was not modified by serotonin depletion. Taking into account these facts it may be considered that the GABAergic system is involved in the stimulatory effect of EAAs on PROL secretion, this effect being independent of the serotoninergic system. 5-HTP significantly increased PROL plasma levels, and this effect was modified neither by the GABAergic nor by the EAAs receptor antagonists. These results indicate that the stimulatory effect of serotonin on PROL release is independent of the GABAergic and EAAs systems. In conclusion it may be considered that in prepubertal female rats, the GABAergic and serotoninergic systems stimulate PROL secretion by independent mechanisms that do not include EAAs. On the other hand, the effects of EAAs neurotransmission are exerted via the GABAergic system.

5-Hydroxytryptophan↗

PubMed2000

[Effect prolonged GABAergic activation on the pubertal development of female rats].

We evaluated, in immature female rats, the effect of the GABAergic system on the reproductive axis and on pubertal development. Initially, using a prolonged treatment with aminooxyacetic acid (AOAA), increasing hypothalamic GABA (p < 0.002), and decreasing GnRH and glutamate content (p < 0.05 and < 0.02). Treated rats showed diminished serum LH (p < 0.05) and estradiol (p < 0.005) levels. Vaginal opening occurred at 30.8 +/- 0.6 days in controls, and at 36.7 +/- 0.98 days in AOAA-treated rats. Acute treatment with AOAA resulted in a decreased GnRH and glutamate output, and in an increased taurine release from superfused hypothalamic fragments. This effect was mimicked by the GABA-A and GABA-B agonists. The activation of the GABAergic system during postnatal days 23-29 significantly restrains the hypothalamo-pituitary-ovaric axis and delays the onset of puberty. The existence of a physiological cross-talk between excitatory and inhibitory amino acid neurotransmitters regulating GnRH release during the onset of puberty is postulated.

Aminooxyacetic Acid↗

PubMed1999

GABAergic activation inhibits the hypothalamic-pituitary-ovaric axis and sexual development in the immature female rat. Associated changes in hypothalamic glutamatergic and taurinergic systems.

The aim of the present studies was to assess, in immature female rats, the effect of the GABAergic system on the reproductive axis and on pubertal development. With this purpose we initially evaluated, in 30-day-old female rats, the effect of persistently enhanced GABAergic activity (aminooxyacetic acid (AOAA) 10 mg/kg per day i.p., during postnatal days 23-29) on hypothalamic gonadotropin-releasing hormone (GnRH) and amino acid neurotransmitter (AANT; glutamate or GLU, and taurine or TAU) concentrations, on circulating luteinizing hormone (LH) and estradiol levels, and on ovaric weight. In a second group of similarly treated rats, the date of vaginal opening (VO) was recorded. Complementary in vitro experiments (superfusion of anterior/mediobasal hypothalamic fragments obtained from rats aged 30 days) were performed to evaluate the effect of the short-term activation of the GABAergic system (by means of AOAA, muscimol or baclofen) on hypothalamic GnRH and AANT release. Prolonged treatment with AOAA led to a marked increase in hypothalamic gamma-aminobutyric-acid (GABA) concentrations (p<0.002), and to a significant decrease in hypothalamic GnRH and GLU content (p<0.05 and <0.02, respectively). Furthermore, treated animals showed diminished serum LH (p<0.05) and estradiol (p<0.005) levels, and a clear reduction in ovaric weight (p<0.002). Mean age at VO was 30. 8+/-0.6 days in control animals (range: 29-34 days), and 36.7+/-0.98 days in AOAA-treated rats (range: 33-40 days; p<0.0001). Acute treatment with AOAA resulted in a decreased GnRH and GLU output, and in an increased TAU release from superfused hypothalamic fragments. This effect was mimicked by the GABA-A and GABA-B agonists. Our results show that the activation of the GABAergic system during postnatal days 23-29 significantly restrains the hypothalamic-pituitary-ovaric axis, resulting in a clear-cut delay in sexual development. This can be attributed to the inhibitory effect exerted by GABA (acting on both GABA-A and GABA-B receptor subtypes) on GnRH release. Furthermore, the pharmacologic manipulation of the GABAergic system induces significant changes in the release of GLU and TAU, giving biochemical support to the existence of a physiological cross-talk between the excitatory and inhibitory AANT regulating GnRH release during the onset of puberty.

Aminooxyacetic Acid↗

PubMed1999

Effects of the GABA-A receptor agonist and antagonist on the in vitro release of hypothalamic catecholamines: apparent parallelism between these effects and the LHRH secretion in adult male rats.

GABA (gamma-aminobutyric acid) has a well-known inhibitory effect on the luteinizing hormone-releasing hormone (LHRH) secretion. In order to evaluate the contribution of the catecholaminergic neurotransmitters on the inhibitory effect produced by GABA on the LHRH release, we measured in adult male rats the in vitro hypothalamic output of LHRH, epinephrine (E), norepinephrine (NE) and dopamine (DA); after the administration of, either muscimol 1 microM (GABA-A agonist), and/or 1 microM bicuculline (GABA-A antagonist). The following results were obtained: muscimol inhibited LHRH secretion, and this effect was accompanied by a decrease of NE, E and DA output. The opposite effects were observed after the addition of bicuculline, i.e, stimulation of LHRH, NE, E and DA release. In conclusion, our results show that, in the adult male rats, GABA has an inhibitory effect on the in vitro release of LHRH, acting on the GABA-A receptor. This effect on LHRH secretion might be exerted directly, or indirectly, by altering the release of either NE,E, and/or DA.

Animals↗

PubMed1998

Interactions between GABAergic and serotoninergic systems with excitatory amino acid neurotransmission in the hypothalamic control of gonadotropin secretion in prepubertal female rats.

The present studies were designed to study the interrelationships between GABAergic, serotoninergic and excitatory amino acids systems (EAAs) in the control of gonadotropin secretion in prepubertal female rats. For this purpose we determined the effects of N-methyl-D-aspartate (NMDA), an exogenous agonist of EAAs receptors, on LH and FSH secretion in 16-day-old female rats in which the GABA-A and GABA-B receptors were blocked by bicuculline and baclofen or serotonin (5-HT) depleted by p-choloroamphetamine (PCA). In addition the effects of the GABAergic and serotoninergic systems on LH and FSH secretion were evaluated in animals treated with dibenzocycloalkenimine (diocilpine MK-801), an antagonist of NMDA neurotransmission. While muscimol, a GABA-A agonist, induced a significant increase in LH and FSH levels (P < 0.01), baclofen, a GABA-B agonist, had an inhibitory effect on these hormones (P < 0.01). MK 801, a NMDA receptor antagonist, not only suppressed the stimulatory effect of NMDA on LH and FSH but also blocked the stimulatory effect of muscimol without modifying the inhibitory action of baclofen on both gonadotropins. Bicuculline, a GABA-A receptor antagonist, did not modify the release effect of NMDA on LH and FSH. 5-HTP, a precursor of 5-HT that increases the levels of this neurotransmitter in the central nervous system significantly increased (P < 0.01) the plasma levels of LH and FSH, and this effect was blocked by the NMDA receptor antagonist MK-801. We conclude that the stimulatory effects of GABAergic and serotoninergic systems in prepubertal female rats are connected with the activation of EAA neurotransmission, while the stimulatory effects of NMDA appear to be independent of serotoninergic and GABAergic actions on LH and FSH secretion. Since both GABA and serotonin systems change their effects on LH and FSH during sexual maturation from a stimulatory action in prepubertal to an inhibitory action in adult rats and since NMDA neurotransmission has a stimulatory effect on gonadotropin secretion both in prepubertal and adult rats, it is clear that the interrelationships between GABAergic and serotoninergic systems with EAAs in the gonadotropin control are different in prepubertal and in adult rats.

5-Hydroxytryptophan↗

PubMed1998

Effect of bacterial endotoxin on in vivo pulsatile gonadotropin secretion in adult male rats.

Immune system disorders are often accompanied by alterations in the reproductive axis. The bacterial endotoxin (lipopolysaccharide or LPS) has central inflammatory effects, and activates cytokine release (immune system mediatory factors) in the hypothalamus, where the luteinizing hormone-releasing hormone neurons are located. The present study was designed to investigate the effect of LPS on the pulsatile release of LH and FSH in adult male rats. With this aim, orchidectomized male rats were implanted with an atrial catheter and received, after two basal blood collections, LPS (250 microg/kg i.v.) or saline. Subsequently, blood samples were taken at regular intervals during 110 min. As expected, LH release was markedly reduced following exposure to LPS. In order to quantify these effects objectively, we subjected these data to PC-pulsar analysis. Pulsatile LH release was clearly disrupted in LPS-treated animals as compared to control rats: pulse frequency 1.3 +/- 0.3 versus 0.43 +/- 0.2/110 min, p < 0.05; pulse amplitude 17.18 +/- 2.2 versus 8.33 +/- 0.66 ng/ml, p < 0.05; overall mean release 15.2 +/- 0.75 versus 7.08 +/- 1.11 ng/ml, p < 0.001; maximum values 27.5 +/- 3.08 versus 9.95 +/- 2.16 ng/ml, p < 0.001; baseline levels 13.83 +/- 0.77 versus 6.55 +/- 0.74 ng/ml, p < 0.001. Regarding FSH secretion, LPS administration significantly lowered baseline levels (p < 0.05) and overall mean release (p < 0.01); FSH pulsatility parameters showed no significant differences. These observations indicate that LPS decreases LH and FSH mean release rates and baseline levels and inhibits several pulsatility parameters of LH release (frequency, amplitude and maximum values); FSH pulsatility parameters are not altered by LPS administration. We speculate that this effect is exerted principally at the hypothalamic level by modifying GnRH secretion.

Animals↗

PubMed1996

Effects of aging on N-methyl-D-aspartate (NMDA)-induced GnRH and LH release in female rats.

In order to evaluate if the changes of the hypothalamic-pituitary-ovary axis that induce a decrease in fertility and modifications in the sexual cycles during senescence involve modifications in the regulatory action of excitatory amino acid neurotransmission on GnRH neurons, we measured the in vitro effects of NMDA on GnRH release by the anterior preoptic and medial basal hypothalamic areas (APOA-MBH) of castrated aging (18 months old) and young (90 days of age) rats. In a second series of experiments the in vivo LH release response to intrahypothalamic (push-pull) administration of NMDA to aged and young castrated female rats was also determined. A similar rate of basal GnRH release was observed in old and young rats during the incubation time. The addition of NMDA to the medium significantly increased GnRH release in both groups; nevertheless, the GnRH release response to NMDA was significantly lower in old (P < 0.01) than in young rats (Young: Basal: 50 +/- 10; NMDA 15': 410 +/- 63, 22,5': 1,469 +/- 300; Old: Basal: 47 +/- 10; NMDA 15': 210 +/- 30; 22,5': 350 +/- 65 ng/GnRH/mg.protein). The LH levels measured throughout the in vivo experiments indicated that basal LH concentrations were significantly lower in the aged group. The mean LH concentrations (fractions 1 to 6) was significantly lower in the aged group (Young: 3.9 +/- 0.07, Old: 2.4 +/- 0.03 ng/ml, P < 0.01). The LH release response to NMDA measured 10 min after the intrahypothalamic administration of the glutamate agonist was significantly lower in aged rats (4.2 +/- 1.6 ng/ml) as compared to young animals (18.0 +/- 6.1 ng/ml; P < 0.05). LH levels in young rats increased to 580% vs., and only 47% in aged rats as compared to previous basal values. In conclusion, present results demonstrate that the GnRH responses to NMDA neurotransmission, which has a predominantly excitatory effects on GnRH neurons, is significantly decreased in old rats, these data give further support to the hypothesis that a decrease in the excitatory inputs to GnRH neurons could be directly involved in the reduction of the hypothalamic-pituitary-ovary axis activity observed during aging.

Aging↗

PubMed1996

Differential effects of the N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors of the excitatory amino acids system on LH and FSH secretion. Its effects on the hypothalamic luteinizing hormone releasing hormone during maturation in male rats.

The present experiments describe the effect of NMDA and kainate agonists of the NMDA and non-NMDA subtype of receptors respectively of the excitatory amino acids (EAAs) system in prepubertal (16 days of age) and peripubertal (30-day-old rats) male rats on the in vitro hypothalamic release of GnRH, and on the in vivo LH and FSH levels as well as the effect of testosterone on these effects. The addition of NMDA or kainate to the medium containing APOA-MBH areas significantly increased (P < 0.01) the GnRH release as compared with the respective controls. The increase in GnRH release observed with kainate was significantly higher (P < 0.01) than those observed with NMDA. NMDA administration increased significantly (P < 0.01) serum LH levels at both ages of sexual maturation while no effect was observed by kainate administration. MK 801, an antagonist of NMDA neurotransmission, and testosterone abolished the LH release response to NMDA. Contrary to that observed on LH, while NMDA did not modify serum FSH concentrations a significant increase (P < 0.01) was observed with kainate administration in prepubertal and peripubertal rats on this pituitary hormone, and CNQX, an antagonist of non-NMDA neurotransmission, and testosterone administrations blocked this FSH release effect of kainate. The NMDA and kainate release effect on LH and FSH respectively was significantly higher in prepubertal than in peripubertal rats. At both ages NMDA released more LH than kainate FSH. In conclusion, our experiments demonstrated that both subtypes of glutamate receptors NMDA and non-NMDA subtypes of EAAs increased GnRH release by APOA-MBH in vitro during sexual maturation. Nevertheless, while NMDA administration only increased serum LH levels, kainate showed only an effect on increasing FSH concentrations. These differential effects of NMDA and non-NMDA subtypes of EAA receptors on LH and FSH could probably explain some aspects of the differential modifications of LH and FSH observed in different physiological circumstances.

Animals↗

PubMed1996

Evidence to suggest that gonadotropin-releasing hormone inhibits its own secretion by affecting hypothalamic amino acid neurotransmitter release.

The mediobasal hypothalamus of rats contains gonadotropin-releasing hormone (GnRH) receptors. These hypothalamic neurons also express the GnRH corresponding gene. Under these circumstances, the possibility exists that these GnRH receptors could be localized in other neurons, which are GnRH-receptive, unknowing the neurotransmitter quality. Therefore, we studied the in vitro effects of the GnRH agonist buserelin on GnRH, glutamate, gamma-amino-butyric acid (GABA) and taurine release from explanted superfused hypothalami of untreated and buserelin-pretreated (down-regulated) male rats. When buserelin was added to the superfusion medium it inhibited promptly the release of GnRH and the excitatory amino acid neurotransmitter glutamate, but stimulated the release of the inhibitory neurotransmitters, GABA and taurine. Hypothalamic release of GnRH from hypothalami collected from buserelin-treated (30 micrograms/100 g b.w. twice daily for 4 days) male rats released significantly less GnRH, glutamate and more GABA and taurine. The inhibitory effect of buserelin was maintained when the superfusion medium continuously contained the GnRH analog. When superfusion of hypothalami from buserelin-pretreated animals was performed in the absence of buserelin, GnRH and glutamate release increased significantly within 45-60 min, whereas GABA and taurine release decreased at this time point. When buserelin was added to the superfusion medium 2 h after buserelin-free superfusion, GnRH and glutamate release decreased whereas GABA and taurine release increased instantaneously. Buserelin-treated rats showed significantly low values of LH and testosterone than the untreated rats. These results suggest that GnRH receptors may not only be present in GnRH axon terminals in the median eminence, but also on glutamatergic, GABAergic and taurinergic neurons by which GnRH may exert an autoinhibitory ultrashort loop feedback on its own secretion. This effect appears to be connected with glutamatergic, GABAergic and taurinergic neurons.

Amino Acids↗

PubMed1996

The GABAergic control of gonadotropin-releasing hormone secretion in male rats during sexual maturation involves effects on hypothalamic excitatory and inhibitory amino acid systems.

In order to evaluate the possible participation of the hypothalamic excitatory and inhibitory amino acid neurotransmitter systems in the GnRH release response to GABAergic drugs, hypothalami (preoptic and mediobasal area) of immature (26 days of age) and adult male rats were perifused with GABA-A and -B agonists and antagonists. GnRH and amino acid neurotransmitter concentrations (glutamate, taurine, GABA) were measured in perfusate samples collected every 15 min during 150 min. In immature rats, muscimol and baclofen (GABA-A and GABA-B agonists, respectively) increased GnRH, glutamate and GABA release and decreased taurine output, while in adults these agonists showed opposite effects on GnRH and glutamate release, and increased GABA and taurine output. On the other hand, in immature rats bicuculline and phaclofen (GABA-A and GABA-B antagonists, respectively) decreased GnRH, glutamate and GABA release, increasing taurine outflow. In adult animals, these antagonists enhanced GnRH and glutamate release, decreasing taurine and GABA outflow. These results indicate that GABA stimulates GnRH release in immature male rats and confirm the inhibitory role of this amino acid neurotransmitter in adult animals. This effect might be associated, at least partially, with the modifications observed in the excitatory and inhibitory amino acid release. On the other hand, in immature rats, stimulation of GABA-A and GABA-B receptors increased GABA release. Although ultrastructural studies have not produced any evidence of GABA-GABA neurointeractions, our results suggest the existence of a positive feedback mechanism of GABA autoregulation active during the prepubertal stage. Participation of this mechanism in the onset of puberty cannot be discarded.

Aging↗

PubMed1995

Repeated intracerebroventricular administration of taurine lowers LH levels and postpones vaginal opening in peripubertal female rats.

UNLABELLED: We investigated the effect of repeated intracerebroventricular injections of taurine (Tau, 0.15 mumol/3 microliters distilled water), administered during postnatal days 23-29, on serum LH levels, and on the hypothalamic content of LHRH and amino acid neurotransmitters (measured by HPLC and electrochemical detection) in 30-day-old female rats (n = 18). Treatment with Tau lowered serum LH (Tau: 0.20 +/- 0.04; CONTROLS: 1.04 +/- 0.21 ng/ml RP3; mean +/- S.E.M.; P < 0.05) as well as hypothalamic LHRH levels (Tau: 82.6 +/- 9.5; controls: 128.7 +/- 14.1 pg/mg wet tissue, P < 0.05). Tau treatment doubled hypothalamic GABA levels (Tau: 31.3 +/- 2.9; CONTROLS: 15.6 +/- 1.2 nmoles/mg wet tissue, P < 0.001). In a second group of animals (n = 13), Tau treatment delayed vaginal opening by more than 2 days (P < 0.05 vs. controls). It is concluded that supplementation with Tau during the fourth postnatal week reduces LHRH/LH secretion and postpones sexual development, perhaps by increasing the activity of the hypothalamic GABAergic system.

Amino Acids↗

PubMed1995

Hypothalamic excitatory amino acid system during sexual maturation in female rats.

The present results indicate that during sexual maturation the APOA-MBH from rats of 30 days of age released significantly higher quantities of GnRH than the tissue from 16-day-old rats (P < 0.01). The addition of NMDA, an agonist of the excitatory amino acids system (EAAs), to the medium after 30 min of incubation significantly increased (P < 0.01) the GnRH release in normal rats of both ages and this increase was significantly (P < 0.01) higher in 30-day-old rats (to 661%) than in rats of 16 days of age (to 273%). The administration of estrogen-progesterone (EP) to rats of 16 days of age did not modify the GnRH release response to NMDA. On the contrary, at 30 days of age EP administration significantly potentiated the GnRH release response to NMDA since while in the control group NMDA increased the GnRH release to 630%, in the EP-pretreated group this was to around 4700% (P < 0.01). EP pretreatment of prepubertal rats decreases the hypothalamic release of aspartate and glutamate, the excitatory amino acids involved in NMDA neurotransmission and glycine but increases EAAs release in peripubertal rats. On the basis of these results it is proposed that the increase in EAAs release by the hypothalamus is directly connected with the onset of puberty and that the maturation of the positive feedback effect of ovarian hormones on gonadotropin secretion is related to the maturation of the capacity of EP to increase hypothalamic EAAs. Before this maturational event EP inhibits EAAs release as well as gonadotropin release (prepubertal rats). NMDA receptor stimulation leads to a positive mechanism which increases the release of Asp and Glu from APOA-MBH both in prepubertal and peripubertal rats, but EP potentiates this mechanism only in peripubertal rats. This could be an additional neuroendocrine mechanism involved in the increase of gonadotropin during sexual maturation which induces the onset of puberty and the preovulatory discharge of these pituitary hormones.

Age Factors↗

PubMed1995

Effect of ovarian hormones on the hypothalamic excitatory amino acids system during sexual maturation in female rats.

The present experiments were designed to study in female rats during sexual maturation: (1) the hypothalamic release of aspartate (Asp), glutamate (Glu) and glycine (Gly) which are the excitatory amino acids (EAAs) involved in NMDA neurotransmission and of taurine (Tau), a putative inhibitory amino acid of GnRH secretion; (2) the relationships between the effect of estrogen-progesterone (EP) on the release of these EAAs and the secretion of gonadotropins, and (3) the effect of hypothalamic NMDA receptor stimulation on EAAs release by the hypothalamus as well as the effect of EP on this release. The release of EAAs by the anterior preoptic and medial-basal hypothalamic areas (APOA-MBH) is significantly higher in peripubertal than in prepubertal rats (p < 0.01). EP treatment in prepubertal rats (16 days of age) decreased LH and FSH plasmatic levels and also the in vitro release of Asp, Glu, Gly and Tau. Contrary to the observations in prepubertal rats, in 30-day-old peripubertal rats the ovarian hormones significantly (p < 0.01) increased the levels of LH and FSH as well as the release to the medium of these amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗