Estrogen, but not progesterone, induces the activity of nitric oxide synthase within the medial preoptic area in female rats.

The control of gonadotropin-releasing hormone (GnRH) secretion depends on the action of ovarian steroids and several substances, including nitric oxide (NO). NO in the medial preoptic area (MPOA) stimulates the proestrus surge of luteinizing hormone (LH). We studied the effect of estrogen (Tamoxifen-TMX) and progesterone (RU-486) antagonists on mRNA and protein expression of NO synthase (NOS), the enzyme that produces NO, as well as its activity within MPOA. Female rats received s.c. injections of TMX (3mg/animal) on first and second days of the estrous cycle (9 am), RU-486 (2mg/animal) on first, second, (8 am and 5 pm) and third days of the estrous cycle (8 am) or oil (controls) and were killed on the third day (5 pm). Real time-PCR and western blotting were performed to study NOS mRNA and protein expressions. The NOS activity was indirectly assessed by measuring the conversion from [(14)C]-L-arginine into [(14)C]-L-citrulline. TMX significantly decreased neuronal NOS (nNOS) mRNA expression (90%), and the activity of NOS, but did not alter nNOS protein expression. Also, TMX significantly decreased LH, FSH, estrogen and progesterone plasma levels. RU-486 nor affected NOS mRNA and protein expressions neither the NOS activity in the MPOA, but reduced FSH levels. The nitrergic system in the MPOA can be stimulated by estrogen whereas TMX decreased NOS activity and mRNA expression. In conclusion, the involvement of the nitrergic system in the MPOA to induce the surge of LH on proestrus depends on the estrogen action to stimulate the mRNA-nNOS expression and the activity of nNOS but it does not seem to depend on progesterone action.

Role of the preoptic carbon monoxide pathway in endotoxin fever in rats.

Recently, we have reported that the heme oxygenase (HO)-carbon monoxide (CO) pathway plays an important role in the genesis of LPS fever, acting through a cGMP signaling pathway in the brain, but the site of action remains unclear. Thus, the present study was designed to test the hypothesis that the HO-CO pathway mediates fever by acting on the preoptic region of the anterior hypothalamus (POA), which is the brain body core temperature (T(c)) controller site. To this end, the T(c) of rats was monitored by biotelemetry before and after pharmacological modulation of the HO-CO pathway. It was observed that intra-POA administration of the HO inhibitor ZnDPBG (5 nmol) produced no thermoregulatory effect and did not affect LPS (100 microg/kg, i.p.) fever compared to the group treated with the ZnDPBG vehicle, indicating that the HO-CO pathway in the POA is not involved in fever. In agreement, intra-POA heme-lysinate (3.8 or 7.6 nmol), which is known to induce the HO-CO pathway, evoked no change in T(c) compared to the vehicle-treated group. In summary, the present results support the idea that the POA is not the brain site where the HO-CO pathway acts as a fever mediator.

A cyclic AMP mechanism mediates the serotonin-induced increase in glutamic acid decarboxylase activity in the preoptic area and hypothalamus.

Previous studies have shown that the injection of 5-hydroxytryptamine (5-HT) into the third ventricle of rats on the afternoon of proestrus increases glutamic acid decarboxylase (GAD) activity in the preoptic area and the hypothalamus. In the present report we examine the adenylate cyclase-cyclic AMP (cAMP) system as mediator of that effect. The increase in GAD activity induced by intraventricular injection of 5-HT was completely blocked by injecting an antiserum against cAMP into the third ventricle 30 min earlier, whereas an injection of serum from normal rabbits was ineffective. On the contrary, activation of adenylate cyclase activity by intraventricular injection of forskolin increased GAD activity, an effect that was also blocked by anti-cAMP serum. Anti-cAMP serum also lowered GAD activity in the preoptic area and hypothalamus when injected on the morning of proestrus but not when injected in the afternoon, when the values of GAD activity were already low. The results suggest that a cAMP mechanism may be involved in the changes in preoptic-area and hypothalamic GAD activity such as the rise in enzyme activity induced by intraventricular injection of 5-HT.

Glutamic acid decarboxylase activity of the preoptic area and hypothalamus is influenced by the serotonergic system.

The effect of the serotonergic system on glutamic acid decarboxylase (GAD) activity of the preoptic area and the hypothalamus was studied in female rats on the day of proestrus. A circadian rhythm of GAD activity was observed with higher values in rats killed at 1130 h than in rats killed at 1500 h. In rats bearing lesions of the median raphe nucleus (MRn), a nucleus that sends 5-hydroxytryptamine nerve terminals to the areas under study decreased GAD activity. On the contrary, electrochemical stimulation of the MRn enhanced GAD activity in intact rats killed at 1500 h, but not in those killed at 1130 h, an effect that was prevented by the injection of the 5-hydroxytryptamine antagonist, methysergide. Furthermore, the injection of 5-hydroxytryptamine into the third ventricle, either in intact rats in the afternoon or in MRn-lesioned rats in the morning, also increased GAD activity. The results of the present study suggest that activation of the serotonergic system increases GAD activity in the preoptic area and hypothalamus.

Fetal brain transplants induce recovery of male sexual behavior in medial preoptic area-lesioned rats.

Male rats received bilateral lesions within the medial preoptic area which completely abolished sexual behavior. Hypothalamic fetal brain transplants gradually restored sexual behavior to prelesion levels by the 6th week after the transplant. Immunocytochemical analyses revealed tyrosine hydroxylase immunoreactivity neurons within the transplanted tissue. These results demonstrate that fetal brain transplants can restore an innate complex behavior in which no spontaneous recovery is observed.