RESUMO
This study investigated the effect of the pre- and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in peripubertal male rats. DEHP at dose of 3 and 30mg/kg bw/day was administered orally to female rat since pregnancy onset until weaning. The male litters were sacrificed at 30 days of age to determine gonadotropin serum level and the hypothalamic contents of the amino acids aspartate and gamma-aminobutyric acid. No changes in gonadotropin, aspartate and gamma-aminobutyric acid levels were detected at the low dose. DEHP 30mg/kg bw/day reduced testis weight and serum FSH, in correlation with a significant increase in the inhibitory GABAergic tone and a reduction in the stimulatory effect of aspartate on gonadotropin level. This study provides unknown data regarding changes in the hypothalamic contents of the amino acid neurotransmitters, which are involved in the neuroendocrine regulation of reproductive axis, in peripubertal male rat offspring from dams exposed to DEHP during gestational and lactational periods. This could be related with the gonadotropin modifications also here described.
Assuntos
Dietilexilftalato/toxicidade , Hormônio Foliculoestimulante/metabolismo , Hipotálamo/metabolismo , Neurotransmissores/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Maturidade Sexual/fisiologia , Aminoácidos/antagonistas & inibidores , Aminoácidos/metabolismo , Animais , Ácido Aspártico/antagonistas & inibidores , Ácido Aspártico/metabolismo , Feminino , Hipotálamo/efeitos dos fármacos , Lactação/efeitos dos fármacos , Lactação/metabolismo , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar , Maturidade Sexual/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
Immune system disorders are often accompanied by alterations in the reproductive axis. Several reports have shown that administration of bacterial lipopolysaccharide (LPS) has central inflammatory effects and activates cytokine release in the hypothalamus where the luteinizing hormone releasing hormone (Gn-RH) neurons are located. The present study was designed to investigate the effect of repeated LPS administration on the neuroendocrine mechanisms of control of the reproductive axis in peripubertal female rats (30-day-old rats). With this aim, LPS (50 mug/kg weight) was administered to the animals during 25, 27 and 29 days of age and sacrificed on 30 day of life. Gn-RH, gamma-amino butyric acid (GABA) and glutamic acid (GLU), two amino acids involved in the regulation of Gn-RH secretion, hypothalamic content were measured. LH and estradiol serum levels were also determined and the day of vaginal opening examined. The results showed a significant increase in Gn-RH and GLU content (p < 0.0001), shared by a reduction of GABA one (p < 0.0001). LH and estradiol serum levels were decreased (p < 0.01, p < 0.001) and delay in the day of vaginal opening was also observed in treated animals. Present results show that repeated LPS administration impaired reproductive function, modifying the neuroendocrine mechanisms of control of the axis in peripubertal female rats.
Assuntos
Lipopolissacarídeos/farmacologia , Reprodução/efeitos dos fármacos , Maturidade Sexual/fisiologia , Animais , Feminino , Ácido Glutâmico/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Ratos , Ratos Wistar , Maturidade Sexual/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
The immune, endocrine and nervous systems are closely interrelated, which allows the organism to respond to different types of stress such as infection. Chronic infectious and inflammatory conditions are often accompanied by an impaired reproductive function. Leptin, a hormone produced by adipose tissue, exerts a regulatory function on the reproductive axis. It has homology with other proinflammatory cytokines and could be modified by lipopolysaccharide (LPS). Therefore, these studies were designed to investigate the effect of LPS administration on the neuroendocrine mechanisms involved in the regulation of the reproductive axis during sexual maturation. Fifteen- and 30-day-old female rats were injected with a single dose of LPS 250 microg/kg (i.p.) and then nitric oxide synthase (NOS) activity, hypothalamic excitatory/inhibitory amino acids and Gn-RH content, serum LH and leptin concentration were studied. In 15-day-old female rats LPS treatment did not modify hypothalamic inducible (iNOS) and constitutive (cNOS) NOS activity, Gn-RH, glutamate (GLU) and GABA content. Also serum LH and leptin levels were not modified. In 30-day-old rats LPS increased iNOS and cNOS activity (p < 0.001) and hypothalamic Gn-RH content (p < 0.001). At this age hypothalamic GABA content was significantly decreased (p < 0.001) without changes in GLU content, and serum LH (p < 0.001) and leptin (p < 0.0001) decreased significantly. In summary, current studies have demonstrated that LPS administration to 15- and 30-day-old female rats results in a different response of the hypothalamus-pituitary-gonadal axis and of the adipose tissue, demonstrating an ontogenic response of the immune-neuroendocrine system to LPS administration.
Assuntos
Infecções Bacterianas/imunologia , Leptina/imunologia , Neuroimunomodulação/imunologia , Sistemas Neurossecretores/imunologia , Reprodução/imunologia , Maturidade Sexual/imunologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Envelhecimento/imunologia , Envelhecimento/metabolismo , Animais , Feminino , Ácido Glutâmico/imunologia , Ácido Glutâmico/metabolismo , Hormônio Liberador de Gonadotropina/imunologia , Hormônio Liberador de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/imunologia , Hipotálamo/metabolismo , Mediadores da Inflamação/farmacologia , Leptina/sangue , Lipopolissacarídeos/farmacologia , Hormônio Luteinizante/sangue , Hormônio Luteinizante/imunologia , Sistemas Neurossecretores/metabolismo , Sistemas Neurossecretores/fisiopatologia , Óxido Nítrico Sintase/imunologia , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Estresse Fisiológico/imunologia , Estresse Fisiológico/metabolismo , Estresse Fisiológico/fisiopatologia , Regulação para Cima/imunologia , Ácido gama-Aminobutírico/imunologia , Ácido gama-Aminobutírico/metabolismoRESUMO
4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats.
RESUMO
Leptin, a peptide hormone secreted by adipocytes that has been proposed as a metabolic signal in the reproductive system, appears to be linked to the different neuroendocrine processes involved in the onset of puberty. We studied the ontogenic effect of administration of leptin (30 mg/kg i.p.) on serum LH levels during different stages of sexual development (7, 30, and 45 days of age) in male rats and on the hypothalamic content of glutamate (GLU) and gamma-aminobutyric acid (GABA) in 30-day-old rats. Leptin induced a significant increase (p < 0.01) in LH levels in 30 days old rats. This hormone stimulatory effect was accompanied by a significant enhancement (p < 0.01) of the hypothalamic content of glutamate, the hypothalamic excitatory aminoacid involved in N-methyl-D-aspartate (NMDA) neurotransmission. No changes in the LH plasma levels were observed in 7- and 45-day-old male rats treated with leptin. MK 801 (0.1 and 0.3 mg/kg i.p.), an antagonist of NMDA receptors of excitatory amino acid system (EAAs), antagonized the stimulatory effect of leptin on LH secretion and on the hypothalamic content of GLU. These results demonstrate that leptin stimulates the reproductive axis in male rats during a determined period of sexual maturation and that NMDA receptors are involved in thefacilitatory action of leptin on the gonadal axis of male rats during sexual maturation.
Assuntos
Hipotálamo/metabolismo , Leptina/farmacologia , Hormônio Luteinizante/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Maturidade Sexual/fisiologia , Animais , Maleato de Dizocilpina/farmacologia , Ácido Glutâmico/metabolismo , Hipotálamo/efeitos dos fármacos , Hormônio Luteinizante/sangue , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Ácido gama-Aminobutírico/metabolismoRESUMO
The objective of the present paper was to determine the effect of leptin on the reproductive axis in adult male rats, as well as the hypothalamic mechanisms involved in this effect. For this purpose, we studied the in vivo effect of leptin in adult male rats on serum LH levels, and the in vitro effect on hypothalamic GnRH and amino acid neurotrasmitter release. For in vivo experiments, animals were injected i.p. with leptin at a dose of 30, 100 and 300 microg/kg. In the in vitro experiments, hypothalamic samples were incubated for 60 min in Earle's medium with leptin: 10(-9), 10(-10) and 10(-12) M for GnRH determination, and 10(-10) M for amino acids evaluation. Finally, we studied the effect of the lowest effective leptin dose on plasma LH levels in peripubertal male rats to compare the effect between this group and adults. Leptin induces significant decreases of serum LH levels with the different studied doses (p < 0.01 vs. control) in adult male rats, while in peripubertal male rats, it induced a significant (p < 0.01 vs. control) increment in serum LH levels. On the other hand, in vitro leptin in adult male rats, significantly decreases GnRH release as well as the hypothalamic release of glutamate (GLU). In contrast, leptin increased the GABA release by this hypothalamus in these animals. These results indicate that leptin has an inhibitory effect on the GnRH-LH axis in adult male rats and this effect appears to be connected with an inhibition of hypothalamic release of GLU (the excitatory amino acid) and a stimulatory effect on GABA release (the inhibitory amino acid). On the other hand, in peripubertal male rats, leptin showed a stimulatory effect.
Assuntos
Ácido Glutâmico/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Leptina/farmacologia , Hormônio Luteinizante/sangue , Ácido gama-Aminobutírico/metabolismo , Animais , Relação Dose-Resposta a Droga , Leptina/administração & dosagem , Leptina/sangue , Hormônio Luteinizante/antagonistas & inibidores , Masculino , Ratos , Ratos Wistar , Maturidade Sexual/fisiologiaRESUMO
OBJECTIVES: To determine the hypothalamic activity of nitric oxide synthase (NOS, the enzyme involved in the synthesis of nitric oxide NO) during sexual maturation in prepubertal (15 days old) and peripubertal female rats (30 days old) as well as the effect of estradiol administration on this neurotransmitter system. METHODS: Hypothalamic samples containing the anterior preoptic and medial basal areas (APOA-MBH) were homogenized with HEPES 20 mM, pH = 7.4 and NOS activity was determined in APO-MBH after 10 minutes of incubation by the conversion of 14C arginine to 14C citrulline. RESULTS: The hypothalamic concentration of NOS is significantly higher in peripubertal than in prepubertal rats. Treatment with EB increased significantly the activity of the enzyme in both groups compared with control and the increases was similar at both ages. CONCLUSIONS: These results clearly demonstrated that the hypothalamic NOS activity increases in peripubertal rats as compared with prepubertal animals. Estradiol has a similar stimulatory effect on hypothalamic NOS activity at both ages of sexual maturation, indicating that the increase in NOS during sexual maturation is connected with the peripubertal increase of estradiol rather than an increase in the sensitivity of the enzyme to the ovarian hormone.
Assuntos
Estradiol/farmacologia , Hipotálamo/enzimologia , Maturidade Sexual/fisiologia , Animais , Feminino , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacosRESUMO
OBJECTIVES: The aim of the present investigation was to determine whether the catecholaminergic system is involved in gabaergic and serotoninergic effects on gonadotrophin secretion during sexual development. To this end, we studied the effect of GABAergic and serotoninergic systems on hypothalamic catecholamine content at different stages of sexual development. METHODS: The effect of GABA A and GABA B agonists and 5-hydroxy-L-tryptophan on hypothalamic noradrenaline and dopamine content were determined in prepubertal (16 days old) and peripubertal (30 days old) rats. RESULTS: At 16 days of age GABA agonists did not modify hypothalamic noradrenaline content, whereas a significant decrease in catecholamine concentration was observed in peripubertal rats at 30 days of age. Similar changes were observed with GABA agonists administration on dopamine hypothalamic levels, i.e no effects at 15 days of age and a significant decrease at 30 days. The administration of 5-hydroxy-l-tryptophan (5-HTP) induced a decrease of hypothalamic concentration of noradrenaline and dopamine at both ages. CONCLUSION: Results indicate that the GABAergic system modifies the hypothalamic catecholamine content in peripubertal but not in prepubertal rats while serotonin has an inhibitory effect at both stages of sexual maturation. Even though both systems induce similar ontogenic modifications on the gonadotrophin axis (stimulatory effect in prepubertal and inhibitory action in peripubertal and adult rats) the present results appear to indicate that GABAergic and serotoninergic systems regulate gonadotrophin secretion by different hypothalamic mechanisms.
Assuntos
Catecolaminas/metabolismo , Hipotálamo/crescimento & desenvolvimento , Hipotálamo/metabolismo , Serotonina/fisiologia , Maturidade Sexual/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Baclofeno/farmacologia , Dopamina/metabolismo , Feminino , Agonistas GABAérgicos/farmacologia , Muscimol/farmacologia , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-B/efeitos dos fármacosRESUMO
OBJECTIVES: To determine the effect of testosterone administration to prepubertal (15 days old) and peripubertal rats (30 days old) on hypothalamic nitric oxide synthetase (NOS), and GnRH release. METHODS: Hypothalamic samples containing the anterior preoptic and medial basal areas (APO-MBH) were incubated for 30 minutes in 500 l of Earle's medium with glucose (1 mg/ml) and bacitracin (20 mM). GnRH was determined by RIA in the medium and NOS activity was determined in APO-MBH after 10 min of incubation by the conversion of (14) C arginine to (14) C citrulline. RESULTS: Treatment with testosterone propionate, significantly decreased NOS hypothalamic activity in prepubertal male rats. ( CONTROL: 58.41 +/- 0.85; Testosterone: 25.61 +/- 1.40, p<0.001) and had no effect in peripubertal male rats (CONTROL 49.28 +/- 1.50; Testosterone 51.48 +/- 5.2 pmoles NO/10 min/hypothalamus). On the other hand, in prepubertal rats the treatment decreased Gn-RH release ( CONTROL: 3.62 +/- 0.23; Testosterone: 1.38 +/- 0.11 (pg/ml medium, p<0.001) and had no effect on Gn-RH release in 30 days old rats ( CONTROL: 3.65 +/- 0.33;Testosterone: 4.15 +/- 0.36 pg/ ml, medium). CONCLUSION: These results clearly demonstrated that testosterone has an inhibitory effect on hypothalamic NOS activity in prepubertal rats while it did not affect the concentration of this neurotransmitter system in peripubertal rats. This pattern is similar to that observed with GnRH hypothalamic release since testosterone has an inhibitory effect in prepubertal rats and did not modify the GnRH release in peripubertal rats. Taking into account the well known stimulatory effect of NO on GnRH and the decrease in the sensitivity of GnRH-gonadotrophin axis to the inhibitory feedback effect of testosterone during sexual maturation and the onset of puberty, it is proposed that the changes here described are connected with maturational modifications in the sexual hormones on-GnRH axis connected with the onset of puberty.
Assuntos
Hormônios Esteroides Gonadais/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Óxido Nítrico/metabolismo , Área Pré-Óptica/metabolismo , Maturidade Sexual/fisiologia , Testosterona/farmacologia , Animais , Ativação Enzimática/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase/metabolismo , Área Pré-Óptica/efeitos dos fármacos , RatosRESUMO
Aminooxyacetic acid (AOAA), an inhibitor of gamma-aminobutyric transaminase, stimulates the in vitro GABA release by medial and anterior preoptic hypothalamic areas in prepubertal female rats (6, 15 and 30 days of age). This increase of GABA release at 15 days of age, was accompanied by a significant increase (P<0.01) in the hypothalamic release of glutamate (GLU) and aspartate (ASP), the excitatory amino acids involved in N-methyl-D-aspartate neurotransmission and a decrease in the release of these excitatory amino acids at 6 and 30 days of age (P<0.01). The increase in the hypothalamic release of GLU and ASP at 15 days of age was accompanied by a significant increase of the plasmatic LH and FSH concentration, while the hypothalamic decrease of excitatory amino acids release induced by AOAA also decreased LH and FSH plasmatic levels at 6 and 30 days of age. In summary, the present results show that in female rats there are differences in the effect of GABAergic system the hypothalamic release of GLU and ASP and on gonadotrophin secretion at different ages of prepubertal period, i.e. an inhibitory effect at 6 and 30 days of age and a stimulatory one at 15 days of age. It is proposed that the different effects of GABA on gonadotrophin secretion in prepubertal rats previously described are connected with ontogenic changes in the interrelationships between GABAergic and NMDA neurotransmission systems during sexual maturation of the hypothalamus in female rats. It is probable that these ontogenic modifications are connected with the maturation of interneuronal connection and/or new receptors activity.