Time-dependent effects of lead on rat reproductive functions

The effects of exposure to lead on endocrine function and the reproductive parameters were studied in pubertal rats treated with 1.0 g l(-1) lead acetate in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to i.v. injections of lead acetate (0.1 mg 100 g(-1) body wt.) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in plasma and in testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LH-releasing hormone content of the median eminence. The density of [I-125]LH/human chorionic gonadotrophin (hCG) binding sites in testicular homogenates was reduced by saturnism in both groups, concomitant with a significantly increased apparent affinity constant of the hormone-receptor complex. These data can be viewed as the result of a mixture of specific lead toxicity (e.g. at the enzyme level) with other more general actions (e.g. at the level of the hypothalamus-pituitary-testicular axis).

HYPOTHALAMIC-LESIONS INCREASE SALINE INGESTION INDUCED BY INJECTION OF ANGIOTENSIN-II INTO AV3V IN RATS

Water and 3% NaCl intake were increased by the injection of 4 ng angiotensin II (ANG II) into the anteroventral third ventricle (AV3V) region of rats. Pretreatment with two specific ANG II receptor antagonists, [octanoyl-Leu8]ANG II and [Leu8]ANG II, significantly reduced ANG II-induced water and saline intake. This inhibition lasted approximately 30 min, with partial recovery at 60 min. In rats with electrolytic lesion of the bilateral ventromedial nucleus of hypothalamus (VMH), the effect of ANG II on water intake was not different from that observed in sham rats, but saline ingestion increased. In summary, the present results show that the AV3V region is an important central structure for ANG II-induced saline ingestion. Lesion of the VMH increases the response to ANG II, showing an interaction between the AV3V region and the VMH in the regulation of salt ingestion.

CARDIOVASCULAR EFFECTS OF CENTRAL CLONIDINE IN CONSCIOUS RATS AFTER HYPOTHALAMIC-LESIONS

The central injection of clonidine (an alpha-2-adrenoceptor agonist) in conscious normotensive rats produces hypertensive responses and bradycardia. The present study was performed to investigate the effect of electrolytic lesions in the anteroventral third ventricle (AV3V) region or in the lateral hypothalamus (LH) on the pressor and bradycardic responses induced by central clonidine in rats. Mean arterial pressure and heart rate were recorded in sham or AV3V-lesioned rats with cerebral stainless steel cannulae implanted into the lateral cerebral ventricle (ICV) or LH. and in sham or bilateral LH-lesioned rats with cannulae-implanted ICV. The injection of clonidine (40 nmol) ICV or into the LH of sham rats produced a pressor response (37 +/- 2-48 +/- 3 mmHg) and bradycardia (-45 +/- 10--93 +/- 6 bpm). After AV3V-lesion (3 and 12 days) or LH-lesion (3 days) the pressor response was abolished and a small hypotensive response was induced by the injection of clonidine (-1 +/- 3--16 +/- 3 mmHg). The bradycardia (-27 +/- 6--57 +/- 11 bpm) was reduced, but not abolished by the lesions. These results show that the AV3V region and LH are important cerebral structures that participate in the excitatory pathways involved in the pressor response to central clonidine in rats. They also suggest that, in the absence of these pressor pathways, the hypotensive responses to central clonidine may appear in conscious rats.

Urocortin in the central nervous system of a primate (Cebus apella): Sequencing, immunohistochemical, and hybridization histochemical characterization

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

LESION OF THE ANTEROVENTRAL 3RD VENTRICLE REGION IMPAIRS THE RECOVERY OF ARTERIAL-PRESSURE INDUCED BY HYPERTONIC SALINE IN RATS SUBMITTED TO HEMORRHAGIC-SHOCK

The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arteria pressure (MAP) after hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion of the anteroventral third ventricle (AV3V) region (4 h, 4 and 20 days). Rats anesthetized with thiopental sodium were bled (about 2.8 ml/100 g) until the MAP was stabilized at the level of 60 mmHg for 30 min. In sham-lesioned rats, MAP increased to 90 mmHg and became stable near this level after intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.). In AV3V-lesioned rats, the same infusion induced a smaller increase in MAP (80 mmHg) and the MAP returned to pre-infusion levels within 30 min. These results show that the AV3V region plays an important role in the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.

AV3V LESION SUPPRESSES THE PRESSOR, DIPSOGENIC AND NATRIURETIC RESPONSES TO CHOLINERGIC ACTIVATION OF THE SEPTAL AREA IN RATS

In the present study we investigated the effect of anteroventral third ventricle (AV3V) lesion on pressor, dipsogenic, natriuretic and kaliuretic responses induced by the injection of carbachol (a cholinergic agonist) into the medial septal area (MSA) of rats. Male rats with sham or AV3V lesion and a stainless-steel cannula implanted into the MSA were used. Carbachol (2 nmol) injected into the MSA in sham lesion rats produced pressor (43 +/- 2 mmHg), dipsogenic (9.6 +/- 1.2 ml/h), natriuretic (531 +/- 82-mu-Eq/120 min) and kaliuretic (164 +/- 14-mu-Eq/120 min) responses. In AV3V-lesioned rats (1-5 days and 14-18 days), the pressor (11 +/- 2 mmHg, respectively), dipsogenic (1.9 +/- 0.7 and 1.4 +/- 0.6 ml/h), natriuretic (21 +/- 5 and 159 +/- 44-mu-Eq/120 min) and kaliuretic (124 +/- 14 and 86 +/- 13-mu-Eq/120 min) responses induced by carbachol injection into the MSA were reduced. These results show that the AV3V region is essential for the pressor, dipsogenic, natriuretic and kaliuretic responses induced by cholinergic activation of the MSA in rats.

Reproductive aspects in female rats exposed prenatally to hydrocortisone

We investigated the effects of hydrocortisone during the prenatal period and its later repercussion on reproductive aspects of female rats. Pregnant rats were treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of pregnancy. Although the present study was not intended to identify mechanisms of toxicity, the treatment with hydrocortisone in the last period of pregnancy presented no signs of toxicity. The efficacy of the hydrocortisone in reducing the adrenal wet mass and plasma corticosterone levels immediately after delivery in both the treated mothers and in respective pups at birth may indicate impairment of the hypothalamus-pituitary-adrenal axis. In addition, the treatment with hydrocortisone did not interfere in the development of the female descendants until puberty. However, it affected the estrous cycle and fertility, Probably, the prenatal exposure to corticosteroids had altered at least partially the hypothalamus-pituitary-gonadal axis, resulting in the damages observed in adult life. These results indicate that the use of the hydrocortisone at a dose that apparently does not endanger the neonate led to undesirable effects in the adult reproductive phase, resulting in later deleterious alteration of the reproductive physiology in female rats. (C) 2004 Elsevier B.V. All rights reserved.

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic ( 5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD- induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD- induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5- HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and nondepleted animals. The OT plasma levels significantly increased only in the PD- induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.

THE EFFECTS OF FOREBRAIN MULTIPLE LESIONS ON THE PRESSOR-RESPONSE INDUCED BY BILATERAL CAROTID OCCLUSION IN CONSCIOUS RATS

In the present study, the effects of electrolytic lesions of the anteroventral third ventricle (AV3V) region and of the medial forebrain bundle (MFB) on the pressor response induced by bilateral carotid occlusion (BCO) in conscious intact and aortic baroreceptor-denervated (AD) rats were investigated. In intact control rats, BCO during 60 s produced a pressor response that could be divided into an early response (ER = 50 +/- 3 mmHg) that reachs a peak during the first 20 s and a sustained late response (LR), smaller than ER (32 +/- 2 mmHg), observed during the last 30 s. In intact-innervated rats, AV3V lesion (2 days) reduced ER (22 +/- 3 mmHg) and LR (16 +/- 2 mmHg), whereas the bilateral MFB lesions (6 days) mainly reduced LR (9 +/- 1 mmHg). Rats with simultaneous lesion of both the AV3V region and the MFB showed additional reduction of the ER (15 +/- 3 mmHg), but not LR (11 +/- 1 mmHg) when compared to the effect of MFB lesions alone. Compared to the AV3V lesion alone, LR but not ER was reduced in rats with a double lesion. In sham-lesioned rats, AD induced a significant increase in the pressor response to BCO (ER = 75 +/- 4 mmHg and LR = 65 +/- 3 mmHg) when compared to intact controls. A similar reduction in ER and LR was observed in AD rats after AV3V (ER = 35 +/- 3 mmHg and LR = 40 +/- 2 mmHg) and MFB (ER = 49 +/- 6 mmHg and LR = 41 +/- 5 mmHg) lesions alone or combined (ER = 40 +/- 6 mmHg and LR = 35 +/- 7 mmHg). The results showed that simultaneous lesions of both the AV3V region and the MFB practically abolished the pressor response to BCO. They also suggested that aortic baroreceptor activity plays a significant role in the effects of AV3V and MFB lesions on the pressor response to BCO.

Effects of maternal exposure to an aromatase inhibitor on sexual behaviour and neurochemical and endocrine aspects of adult male rat

The present study examined the effects of letrozole exposure during brain sexual differentiation on endocrine, behavioural and neurochemical parameters in male rat descendants. Pregnant female rats received 1 mg kg(-1) day(-1) letrozole or vehicle by oral gavage on gestational Days 21 and 22. Exposure to letrozole reduced anogenital distance in males on postnatal Day (PND) 22. At adulthood (PND 75), plasma testosterone levels and hypothalamic dopaminergic activity were increased, but sexual competence was impaired, because fewer successful sexual behaviours (mount, intromission and principally ejaculation) were observed. The impairment of reproductive function by prenatal exposure to an aromatase inhibitor reinforces the importance of adequate oestrogenic activity during perinatal sexual differentiation for complete masculinisation of the hypothalamus.

Impact of breed and sex on porcine endocrine transcriptome: a bayesian biometrical analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Interaction between the lateral preoptic area and the subfornical organ in the control of water ingestion caused by cellular dehydration, hypotension, hypovolemia, and deprivation

Water intake was studied in albino rats with lesions in the lateral preoptic area, in the subfornical organ, and in both the lateral preoptic area and the subfornical organ. Drinking was induced by cellular dehydration, hypovolemia, hypotension (isoproterenol or caval ligation), and water deprivation. The animals with lesions in both areas showed a significant reduction in their water intake in response to cellular dehydration. Drinking due to extracellular dehydration was reduced in the animals that received only subfornical organ lesions, and was reduced even further in the animals with both areas ablated. The lesions in the subfornical organ were sufficient to reduce the thirst induced by caval ligation. The lesions in both areas inhibit water intake induced by caval ligation. Water intake induced by deprivation was reduced when both areas were destroyed. These findings demonstrate that both the lateral preoptic area and the subfornical organ are necessary for normal drinking in response to cellular dehydration, hypovolemia, and hypotension. There is further evidence that the lateral preoptic area and subfornical organ interact in the control of water intake induced by a variety of thirst challenges.

Effect of AV3V lesion on the cardiovascular, fluid, and electrolytic changes induced by activation of the lateral preoptic area

In this study we investigated the effect of the anteroventral third ventricle (AV3V) lesion on the pressor, bradycardic, natriuretic, kaliuretic, and dipsogenic responses induced by the injection of the cholinergic agonist carbachol into the lateral preoptic area (LPOA) in rats. Male Holtzman rats with sham or electrolytic AV3V lesion were implanted with stainless steel cannula directly into the LPOA. Injection of carbachol (7.5 nmol) into the LPOA of sham rats induced natriuresis (405 ± 66 μEq/120 min), kaliuresis (234 ± 44 μEq/120 min), water intake (9.5 ± 1.7 ml/60 min), bradycardia (-47 ± 11 bpm), and increase in mean arterial pressure (28 ± 3 mmHg). Acute AV3V lesion (1-5 days) reduced the natriuresis (12 ± 4 μEq/120 min), kaliuresis (128 ± 27 μEq/120 min), water intake (1.7 ± 0.9 ml/60 min), and pressor responses (14 ± 4 mmHg) produced by carbachol into the LPOA. Tachycardia instead of bradycardia was also observed. Chronic (14-18 days) AV3V lesion reduced only the pressor response (10 ± 2 mmHg) induced by carbachol. These results showed that acute, but not chronic, AV3V lesion reduced the natriuretic, kaliuretic, and dipsogenic responses to carbachol injection into the LPOA. The pressor response was reduced in acute or chronic AV3V-lesioned rats. The results suggest that the lateral areas may control the fluid and electrolyte balance independently from the AV3V region in chronic AV3V-lesioned rats. © 1992.