RESUMO
BACKGROUND: Muscarinic receptors (mAChRs) of the preoptic and anterior hypothalamus areas (POA-AHA) regulate ovulation in an asymmetric manner during the estrous cycle. The aims of the present study were to analyze the effects of a temporal blockade of mAChRs on either side of the POA-AHA performed in diestrus-2 rats on ovulation, the levels of estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) and the mechanisms involved in changes in ovulation. METHODS: Cyclic rats on diestrus-2 day were anesthetized and randomly assigned to the following groups: 1) microinjection of 1 µl of saline or atropine solution (62.5 ng) in the left or right POA-AHA; 2) removal (unilateral ovariectomty, ULO) of the left (L-ULO) or right (R-ULO) ovary, and 3) rats microinjected with atropine into the left or right POA-AHA plus L-ULO or R-ULO. The ovulation rate and the number of ova shed were measured during the predicted estrus, as well as the levels of estradiol, FSH and LH during the predicted proestrus and the effects of injecting synthetic LH-releasing hormone (LHRH) or estradiol benzoate (EB). RESULTS: Atropine in the left POA-AHA decreased both the ovulation rate and estradiol and LH levels on the afternoon of proestrus, also LHRH or EB injection restored ovulation. L- or R-ULO resulted in a lower ovulation rate and smaller number of ova shed, and only injection of LHRH restored ovulation. EB injection at diestrus-2 restored ovulation in animals with L-ULO only. The levels of estradiol, FSH and LH in rats with L-ULO were higher than in animals with unilateral laparotomy. In the group microinjected with atropine in the left POA-AHA, ovulation was similar to that in ULO rats. In contrast, atropine in the right POA-AHA of ULO rats blocked ovulation, an action that was restored by either LHRH or EB injection. CONCLUSIONS: These results indicated that the removal of a single ovary at noon on diestrus-2 day perturbed the neuronal pathways regulating LH secretion, which was mediated by the muscarinic system connecting the right POA-AHA and the ovaries.
Assuntos
Núcleo Hipotalâmico Anterior/metabolismo , Diestro/metabolismo , Estradiol/metabolismo , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Ovulação/metabolismo , Área Pré-Óptica/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Núcleo Hipotalâmico Anterior/efeitos dos fármacos , Atropina/farmacologia , Anticoncepcionais/farmacologia , Diestro/efeitos dos fármacos , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Ovariectomia , Ovário/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Proestro/efeitos dos fármacos , Proestro/metabolismo , Ratos , Receptores Muscarínicos/efeitos dos fármacosRESUMO
Azadirachta indica is a tree whose medicinal value is unquantifiable. Any part of the tree can be used in the treatment of malarial infection. Reports have indicated its antifertility effects, and this necessitated this study on the effects of the methanol leaf extract on serum luteinizing (LH) and follicle stimulating hormones (FSH) levels and the histomorphology of the pars anterior of Wistar rats. Thirty adult male Wistar rats were equally divided into 3 groups of A, B and C. Group A was the control and the animals received distilled water orally, while groups B and C were treated with 200mg/kg and 400mg/kg respectively of the leaf extract by oral gavage for fourteen days. On day fifteen, the animals were sacrificed by chloroform anaesthesia. Blood was obtained from their hearts, while the skull was opened to assess the hypophysis. Hormonal assay showed that luteinizing (LH) and follicle stimulating (FSH) hormone levels in the serum were lower in groups B and C treated with 200mg/kg and 400mg/kg respectively of the leaf extract, while that of LH were significant (P<0.001). Histomorphologic sections of the pars anterior revealed reduced acidophil and basophil populations, with prominent degranulated chromophobes which were larger in the group treated with 400mg/kg of A. indica leaf extract. This group also presented hypertrophy of the basophils compared to the control. In conclusion, methanol leaf extract of A. indica decreases serum LH and FSH and caused histomorphologic changes in the pars anterior of adult male Wistar rats.
Azadirachta indica es un árbol cuyo valor medicinal es invaluable. Cualquier parte del árbol se puede utilizar en el tratamiento de la infección por malaria. Reportes han indicado su efecto antifertilidad, lo que requirió estudiar los efectos del extracto metanólico de la hoja sobre los niveles séricos de las hormonas luteinizante (LH) y folículo estimulante (FSH) y la histomorfología de la pars anterior de ratas Wistar. Treinta ratas Wistar adultas fueron divididas en tres grupos. El grupo A fue utilizado como control y los animales recibieron agua destilada por vía oral, mientras que los grupos B y C fueron tratados con 200 mg/kg y 400 mg/kg respectivamente, con extracto de hoja mediante una sonda nasogástrica durante catorce días. A los quince días, los animales fueron sacrificados por anestesia con cloroformo. Se obtuvo sangre desde sus corazones, mientras que el cráneo fue abierto para evaluar la hipófisis. Los ensayos hormonales mostraron que los niveles en suero de la LH y FSH se redujeron en los grupos B y C, tratados con 200 mg/kg y 400 mg/kg respectivamente, siendo la reducción de LH significativa (p<0,001). Secciones histomorfológicos de la pars anterior revelaron una reducción de las poblaciones acidófilas y basófilas, con prominentes cromófobos degranulados que fueron mayores en el grupo tratado con 400 mg/kg del extracto de A. indica. Este grupo también presentó hipertrofia de los basófilos en comparación con el control. En conclusión, el extracto alcohólico de la hoja de de A. indica disminuye el nivel sérico de LH y FSH y provoca cambios histomorfológicos en la pars anterior de ratas Wistar adultas.
Assuntos
Animais , Masculino , Ratos , Adeno-Hipófise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Azadirachta , Hormônio Luteinizante/efeitos dos fármacos , Hormônio Luteinizante/sangue , Ratos Wistar , Folhas de Planta , Hormônio Foliculoestimulante/sangueRESUMO
To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group): distilled water, Butea superba (BS)-10, BS-50, BS-250, and testosterone propionate (TP). They received 0, 10, 50, and 250 mg·kg body weight-1·day-1 BS in distilled water by gavage and 6 mg·kg body weight-1·day-1 TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.
Assuntos
Animais , Masculino , Ratos , Butea/química , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Extratos Vegetais/farmacologia , Testosterona/sangue , Hormônio Luteinizante/efeitos dos fármacos , Orquiectomia , Tamanho do Órgão/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Radioimunoensaio , Ratos Wistar , Glândulas Seminais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Propionato de Testosterona/farmacologiaRESUMO
To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group): distilled water, Butea superba (BS)-10, BS-50, BS-250, and testosterone propionate (TP). They received 0, 10, 50, and 250 mg·kg body weight(-1)·day(-1) BS in distilled water by gavage and 6 mg·kg body weight(-1)·day(-1) TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.
Assuntos
Butea/química , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Extratos Vegetais/farmacologia , Testosterona/sangue , Animais , Hormônio Luteinizante/efeitos dos fármacos , Masculino , Orquiectomia , Tamanho do Órgão/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Radioimunoensaio , Ratos , Ratos Wistar , Glândulas Seminais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Propionato de Testosterona/farmacologiaRESUMO
OBJECTIVE: To compare the pulsatile release of LH, the tone of endogenous opioids and the mass of LH secreted after a naloxone infusion in healthy subjects and patients with normogonadotropic oligospermia (NO) in a model of progressive testicular damage. PATIENTS AND METHODS: Pulsatile secretion of LH was analyzed in a period of 8 hours in a group of healthy subjects (group 3, n=5), in patients with NO and FSH/LH ratio <1.6 (group 1, n=5) and in patients with NO and FSH/LH ratio >1.6 (group 2, n=5). The area under the curve of LH response after naloxone infusion was also calculated. RESULTS: Free serum testosterone concentration was lower (p < 0.01) and estradiol concentration higher in patients with NO than control subjects (1 vs. 3: p = 0.01; 2 vs. 3: p = 0.001). Frequency of pulses in group 1 was 3.33 +/- 0.57/8 h, in group 2: 4 +/- 1/8 h; and in group 3: 2.66 - 0.57/8 h (2 vs. 3 p < 0.01; 2 vs. 1 p = 0.05). The area under the curve after naloxone infusion was 19,300.44 +/- 11,403.31 in group 1, 5696.09 +/- 1753.44 in group 2; and 3080.97 +/- 1159.78 in group 3 (1 vs. 3 Anova p = 0.01). CONCLUSIONS: The data indicate that patients with NO have a subclinical pantesticular failure and that the opioid tone is increased at the initial phase of testicular dysfunction, but it decreases at more advanced stages of testicular damage.
Assuntos
Hormônio Luteinizante/efeitos dos fármacos , Hormônio Luteinizante/metabolismo , Naloxona/farmacologia , Oligospermia/fisiopatologia , Doenças Testiculares/fisiopatologia , Estradiol/sangue , Humanos , Masculino , Oligospermia/sangue , Peptídeos Opioides/sangue , Doenças Testiculares/sangue , Testosterona/sangueRESUMO
Although evidence is accumulating that prenatal testosterone (T) compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 microg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC) of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01). The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05). AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05). Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring.
Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Gônadas/efeitos dos fármacos , Leuprolida/farmacologia , Hormônio Luteinizante/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Testosterona/farmacologia , Animais , Área Sob a Curva , Feminino , Hormônio Luteinizante/sangue , Masculino , Gravidez , Ovinos , Testosterona/sangue , Fatores de TempoRESUMO
Although evidence is accumulating that prenatal testosterone (T) compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 µg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC) of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01). The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05). AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05). Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring.
Assuntos
Animais , Feminino , Masculino , Gravidez , Hormônio Liberador de Gonadotropina/agonistas , Gônadas/efeitos dos fármacos , Leuprolida/farmacologia , Hormônio Luteinizante/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Testosterona/farmacologia , Área Sob a Curva , Hormônio Luteinizante/sangue , Ovinos , Fatores de Tempo , Testosterona/sangueRESUMO
We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.
Assuntos
Animais , Feminino , Ratos , Antagonistas Adrenérgicos alfa/farmacologia , Hormônio Luteinizante/sangue , Prazosina/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Injeções Intraventriculares , Hormônio Luteinizante/efeitos dos fármacos , N-Metilaspartato/antagonistas & inibidores , Norepinefrina , Ovariectomia , Postura/fisiologia , Ratos Sprague-Dawley , Comportamento Sexual Animal/fisiologiaRESUMO
We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 microg/6 microL) prior to NMDA administration (1 microg/2 microL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 +/- 3.28, N = 28) when compared to saline controls (6 and 2 microL, 16.59 +/- 3.20, N = 27) was abolished by prazosin administration (17.04 +/- 5.52, N = 17, and 9.33 +/- 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 +/- 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 +/- 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Hormônio Luteinizante/sangue , Prazosina/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Feminino , Injeções Intraventriculares , Hormônio Luteinizante/efeitos dos fármacos , N-Metilaspartato/antagonistas & inibidores , Norepinefrina/metabolismo , Ovariectomia , Postura/fisiologia , Ratos , Ratos Sprague-Dawley , Comportamento Sexual Animal/fisiologiaRESUMO
There is evidence that alpha-melanocyte-stimulating hormone (alpha-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of alpha-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 microg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by alpha-MSH (3 nmol/rat) injected 30 min before LPS. alpha-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of alpha-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of alpha-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by alpha-MSH. Both LPS and alpha-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and alpha-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of alpha-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 microg/ml) and LPS plus interferon-gamma (IFN-gamma, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-gamma. This stimulatory effect was attenuated in the presence of alpha-MSH (5 microM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that alpha-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous alpha-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.