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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.

We investigated the effect of ovariectomy (OVX) and subsequent estradiol benzoate (EB) treatment upon the N-methyl-D-aspartate (NMDA)-induced LH secretion in adult female rats. Furthermore, the release of LHRH, norepinephrine (NE), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA) and γ-aminobutyric acid (GABA) from superfused hypothalamic fragments ex-planted from OVX and OVX-EB rats was determined. Two weeks after OVX, animals received EB (100 mg/kg) s.c, or oil vehicle (OVX-EB or OVX groups, respectively). Two days thereafter, at 09.00 h, NMDA (15 or 30 mg/ kg) was given as an i.v. bolus; blood samples were drawn before and 10 min after drug administration. In OVX rats, NMDA had no significant effect on LH levels, whereas it stimulated LH release in OVX-EB animals at both doses tested (315 and 362% from basal values, p < 0.001). For hypothalamic super-fusion studies OVX and OVX-EB animals were decapitated at 09.00 h, and the mediobasal hypothalami (MBH) dissected on ice. NMDA (10-4 M) was added to the superfusion medium for a 10 min period. Basal LHRH release (OVX: 1.41 ± 0.18; OVX-EB: 1.59 ± 0.28 pg/10 min/MBH) was significantly (p < 0.05) enhanced by NMDA (OVX: 2.97 ± 0.95; OVX-EB: 2.80 ± 0.61 pg/10 min/MBH). EB treatment had no significant effect on basal or NMDA-induced LHRH output. NMDA significantly (p < 0.05) decreased NE (OVX: 30.8 ± 6.7%; OVX-EB: 47.5 ± 9.7% from basal values), DA (OVX: 63.8 ± 10.7%; OVX-EB: 39.7 ± 14.6% from basal values), and 5-HIAA(OVX: 52.6 ± 7.7%; OVX-EB: 57.5 ± 9.7% from basal values) release, and increased GABA output (OVX: 155.6 ± 16.7%; OVX-EB: 183.1 ± 19.2% from basal values). The observation that OVX-EB rats show a massive LH release after NMDA, and that EB treatment does not alter NMDA-induced LHRH secretion, indicates that the predominant site of action of estradiol is exerted within the pituitary. The physiological implications of the NMDA-induced changes in neurotransmitter release remain to be studied.

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 µg/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.