RESUMEN
We examined the role of the estrogen receptors alpha (ERα) and beta (ERß) in of the preoptic-anterior hypothalamic area (POA-AHA) in the regulation of ovulation in rats. The number of ERα- and ERß-immunoreactive (-ir) cells was determined at 09:00, 13:00, and 17:00 h of each stage of the estrous cycle in intact rats. Additionally, the effects of blocking ERα and ERß on ovulation rate at 09:00 h on diestrus-2 or proestrus day through the microinjection of methyl-piperidino-pyrazole (MPP) or cyclofenil in either side of POA-AHA were evaluated. The number of ERα-ir and ERß-ir cells in POA-AHA varied in each phase of estrous cycle. Either MPP or cyclofenil in the right side of POA-AHA on diestrus-2 day reduced the ovulation rate, while at proestrus day it was decreased in rats treated in either side with MPP, and in those treated with cyclofenil in the left side. MPP or cyclofenil produced a decrease in the surge of luteinizing hormone levels (LH) and an increase in progesterone and follicle stimulating hormone (FSH). Replacement with synthetic luteinizing hormone-releasing hormone in non-ovulating rats treated with MPP or cyclofenil restored ovulation. These results suggest that activation of estrogen receptors on the morning of diestrus-2 and proestrus day asymmetrically regulates ovulation and appropriately regulates the secretion of FSH and progesterone in the morning and afternoon of proestrus day. This ensures that both, the preovulatory secretion of LH and ovulation, occur at the right time.
Asunto(s)
Núcleo Hipotalámico Anterior/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Ovulación , Área Preóptica/metabolismo , Animales , Núcleo Hipotalámico Anterior/efectos de los fármacos , Estradiol/sangre , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor beta de Estrógeno/antagonistas & inhibidores , Ciclo Estral/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ovulación/efectos de los fármacos , Óvulo/efectos de los fármacos , Óvulo/metabolismo , Área Preóptica/efectos de los fármacos , Progesterona/sangre , RatasRESUMEN
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.
Asunto(s)
Núcleo Hipotalámico Anterior/metabolismo , Diestro/metabolismo , Estradiol/metabolismo , Hormona Folículo Estimulante/metabolismo , Hormona Luteinizante/metabolismo , Ovulación/metabolismo , Área Preóptica/metabolismo , Receptores Muscarínicos/metabolismo , Animales , Núcleo Hipotalámico Anterior/efectos de los fármacos , Atropina/farmacología , Anticonceptivos/farmacología , Diestro/efectos de los fármacos , Estradiol/análogos & derivados , Estradiol/farmacología , Femenino , Hormona Liberadora de Gonadotropina/farmacología , Hormona Luteinizante/efectos de los fármacos , Antagonistas Muscarínicos/farmacología , Ovariectomía , Ovario/efectos de los fármacos , Ovulación/efectos de los fármacos , Área Preóptica/efectos de los fármacos , Proestro/efectos de los fármacos , Proestro/metabolismo , Ratas , Receptores Muscarínicos/efectos de los fármacosRESUMEN
The hypothalamus plays especially important roles in various endocrine, autonomic, and behavioral responses that guarantee the survival of both the individual and the species. In the rat, a distinct hypothalamic defensive circuit has been defined as critical for integrating predatory threats, raising an important question as to whether this concept could be applied to other prey species. To start addressing this matter, in the present study, we investigated, in another prey species (the mouse), the pattern of hypothalamic Fos immunoreactivity in response to exposure to a predator (a rat, using the Rat Exposure Test). During rat exposure, mice remained concealed in the home chamber for a longer period of time and increased freezing and risk assessment activity. We were able to show that the mouse and the rat present a similar pattern of hypothalamic activation in response to a predator. Of particular note, similar to what has been described for the rat, we observed in the mouse that predator exposure induces a striking activation in the elements of the medial hypothalamic defensive system, namely, the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus. Moreover, as described for the rat, predator-exposed mice also presented increased Fos levels in the autonomic and parvicellular parts of the paraventricular hypothalamic nucleus, lateral preoptic area and subfornical region of the lateral hypothalamic area. In conclusion, the present data give further support to the concept that a specific hypothalamic defensive circuit should be preserved across different prey species.
Asunto(s)
Reacción de Fuga/fisiología , Reacción Cataléptica de Congelación/fisiología , Hipotálamo/metabolismo , Conducta Predatoria/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Núcleo Hipotalámico Anterior/metabolismo , Núcleo Hipotalámico Anterior/fisiología , Conducta Animal/fisiología , Núcleo Hipotalámico Dorsomedial/metabolismo , Núcleo Hipotalámico Dorsomedial/fisiología , Miedo/fisiología , Área Hipotalámica Lateral/metabolismo , Área Hipotalámica Lateral/fisiología , Hipotálamo/fisiología , Inmunohistoquímica , Masculino , Ratones , Vías Nerviosas/metabolismo , Vías Nerviosas/fisiología , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/fisiología , Área Preóptica/metabolismo , Área Preóptica/fisiología , Proteínas Proto-Oncogénicas c-fos/análisis , Ratas , Ratas Long-Evans , Especificidad de la Especie , Núcleo Hipotalámico Ventromedial/metabolismo , Núcleo Hipotalámico Ventromedial/fisiologíaRESUMEN
1. The aim of the present study was to investigate the activity of anterior hypothalamic beta-adrenoceptors and angiotensin (Ang) II receptors on blood pressure in normotensive rats and aortic-coarctated (ACo) animals at a chronic stage of hypertension. A possible interaction between beta-adrenoceptors and AngII pressor activity was also investigated. 2. Injection of isoproterenol (0.1-10 nmol) in the anterior hypothalamic area induced a dose-dependent decrease in mean arterial pressure (MAP) in sham-operated (SO), but not in ACo, animals. Isoproterenol (1 nmol) reduced blood pressure in SO rats (DeltaMAP -10.1+/-1.4 mmHg; n=10) but not in ACo animals (DeltaMAP -0.9+/-1.6 mmHg; n=10; P<0.05 vs SO rats). Whereas previous administration of atenolol (40 nmol) enhanced the cardiovascular effect of isoproterenol (1 nmol) in ACo rats but not in SO animals, propranolol (40 nmol) prevented the hypotensive action of isoproterenol in both experimental groups. Intrahypothalamic administration of clenbuterol decreased MAP in a dose-dependent manner; however, the depressor response to clenbuterol (10 nmol) was greater in ACo rats than in SO rats (DeltaMAP -26.8+/-3.2 vs -14.4+/-2.4 mmHg, respectively; n=5 for both; P<0.05). When AngII (50 ng) was injected into the anterior hypothalamic area, a greater pressor response was observed in ACo rats than in SO rats (DeltaMAP 19.6+/-1.1 vs 11.3+/-0.6 mmHg, respectively; n=5 for both; P<0.05). Atenolol (40 nmol) pretreatment partially and significantly prevented the pressor response to AngII in ACo rats, but not in SO rats. 3. In conclusion, these results provide pharmacological evidence for the existence of a beta1-adrenoceptor-mediated pressor mechanism in the anterior hypothalamic area of ACo rats that is absent in SO rats. The enhanced depressor beta2-adrenoceptor activity observed in chronic ACo rats could be a compensatory adjustment to pressor beta1-adrenoceptor activity. Conversely, pressor overactivity of AngII was observed in the anterior hypothalamic area of ACo rats at a chronic hypertensive stage; this enhancement could be explained, at least in part, by the pressor beta1-adrenoceptor activity.
Asunto(s)
Angiotensina II/metabolismo , Núcleo Hipotalámico Anterior/metabolismo , Coartación Aórtica/metabolismo , Hipertensión/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores de Angiotensina/metabolismo , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacología , Animales , Coartación Aórtica/complicaciones , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Enfermedad Crónica , Clenbuterol/administración & dosificación , Clenbuterol/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hipertensión/complicaciones , Isoproterenol/administración & dosificación , Isoproterenol/farmacología , Microinyecciones , Ratas , Ratas WistarRESUMEN
The existence of endothelin binding sites on the catecholaminergic neurons of the hypothalamus suggests that endothelins (ETs) participate in the regulation of noradrenergic transmission modulating various hypothalamic-controlled processes such as blood pressure, cardiovascular activity, etc. The effects of ET-1 and ET-3 on the neuronal release of norepinephrine (NE) as well as the receptors and intracellular pathway involved were studied in the rat anterior hypothalamus. ET-1 (10 nM) and ET-3 (10 nM) diminished neuronal NE release and the effect blocked by the selective ET type B receptor antagonist BQ-788 (100 nM). N(omega)-nitro-L-arginine methyl ester (10 microM), methylene blue (10 microM), and KT5823 (2 microM), inhibitors of nitric oxide synthase activity, guanylate cyclase, and protein kinase G, respectively, prevented the inhibitory effects of both ETs on neuronal NE release. In addition, both ETs increased nitric oxide synthase activity. Furthermore, 100 microM picrotoxin, a GABA(A)-receptor antagonist, inhibited ET-1 and ET-3 response. Our results show that ET-1 as well as ET-3 has an inhibitory neuromodulatory effect on NE release in the anterior hypothalamus mediated by the ET type B receptor and the involvement of a nitric oxide-dependent pathway and GABA(A) receptors. ET-1 and ET-3 may thus diminish available NE in the synaptic gap leading to decreased noradrenergic activity.