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Biomedical subjects

M M Valença

Publications and source records attributed to M M Valença.

13 recordsLinked to original sources

Experimental murine schistosomiasis and thyroid function.

In humans the hepatosplenic form of schistosomiasis may be associated with some degree of somatosexual underdevelopment. In the present study we induced an experimental hepatosplenic form of schistosomiasis by infecting 21-day-old mice with the São Lourenço da Mata-PE strain of Schistosoma mansoni and evaluated thyroid function and its relationship with somatosexual development. Plasma levels of T3 and T4 were determined in 115-day old male albino Swiss mice by radioimmunoassay as a measure of thyroid function. Prepuberal infection with S. mansoni resulted in significant increases in liver (74%) and spleen (138%) weights, although there were no changes in animal growth or plasma T3 and T4 concentrations under the experimental conditions used. The present study demonstrates that prepuberal infection of mice with S. mansoni induces the development of a hepatosplenic form of schistosomiasis during adult life with apparently normal thyroid function.

Animals↗

Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone-secreting neurons.

Mammalian reproduction is dependent upon intermittent delivery of luteinizing hormone-releasing hormone (LHRH) to the anterior pituitary. This mode of secretion is required to sensitize maximally the gonadotrophs to LHRH stimulation and to regulate gonadotropin gene expression. While LHRH secretion is pulsatile in nature, the origin of the pulse generator is unknown. In this report, we show that this oscillator could be located within the LHRH neuronal network. When immortalized LHRH neurons are placed into a perifusion system, LHRH is secreted into the medium in a pulsatile fashion under basal conditions. LHRH secretion and the number of LHRH pulses are reduced when calcium is removed from the medium. Perifusion also influences pro-LHRH processing, since the molar ratio of its processed products varies dramatically when the cells are transferred from a static system. Several different cellular mechanisms may underlie these changes in secretion and processing. Lucifer yellow experiments reveal that some cells are dye-coupled. Hence, these cells could be electrically coupled through gap junctions such that secretion from individual cells could be coordinated. Secretion could also be synchronized through the observed synapse-like contacts. These contacts could perform a negative-feedback role to regulate not only the amount of LHRH released but also the molecular forms secreted. The organization of LHRH neurons into interconnected clusters could serve to coordinate LHRH secretion from individual cells and, thereby, orchestrate functions in vivo as diverse as the onset of puberty, the timing of ovulation, and the duration of lactational infertility.

Calcium↗

Immortalized hypothalamic gonadotropin-releasing hormone neurons.

The neuroendocrine hypothalamus has been intensively studied using whole animals and tissue slices. However, it has been difficult to approach questions at the molecular and cellular level. By targeting expression of the oncogene product, simian virus 40 T antigen, in transgenic mice using the regulatory domain of the rat gonadotropin-releasing hormone (GnRH) gene, we have produced specific hypothalamic tumours. These tumours have been cultured to produce clonal cell lines (GT-1 cells) that express T antigen, GnRH and many other neuronal markers, but do not express other hypothalamic hormones. These immortal cell lines have a distinctive neuronal phenotype, process the GnRH peptide accurately and secrete GnRH in a pulsatile pattern. Thus, by targeting oncogenesis to a defined population of neurons using the regulatory region of a gene that is expressed late in differentiation of that cell lineage, we have succeeded in immortalizing hypothalamic GnRH neurons. The GT-1 cell lines are an excellent model for future molecular, cell biological, physiological and biochemical investigations into the mechanisms involved in regulation of GnRH and the characteristics of an isolated central nervous system neuron. Their derivation demonstrates the utility of targeting tumorigenesis to specific differentiated neurons of the central nervous system in transgenic mice.

Animals↗

Role of substance P in the medial preoptic area in the regulation of gonadotropin and prolactin secretion in normal or orchidectomized rats.

The present studies were designed to evaluate the role of substance P (SP) in the control of the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). SP was microinjected into the medial preoptic area (MPOA) of conscious, freely moving intact or orchidectomized (ORCX; 21 days post-ORCX) adult male rats. Microinjection of SP into the MPOA induced a significant decrease in plasma LH and FSH concentrations, effects which were accompanied by an elevation in plasma PRL concentration. To examine the participation of endogenously secreted SP in the activity of the MPOA neurons controlling release of these cited pituitary hormones, another study was performed in which either a potent and specific antagonist to SP (D-Pro2, D-Trip7,9-SP; SP-ANT) or an antibody against SP (SP-AB), was injected into the MPOA. SP-ANT and SP-AB both elevated plasma LH, FSH and decreased plasma PRL concentration. These data suggest that endogenous SP within the MPOA exerts an important inhibitory tonus over LH and FSH release and an excitatory tonus over PRL release. In conclusion, SP seems to participate as a neurotransmitter or neuromodulater in the control of LH, FSH and PRL secretion, at least in part, by acting at the level of MPOA, a region in which the neuronal cell bodies that produce LH-releasing hormone and the associated gonadotropin-releasing hormone-associated peptide are located.

Animals↗

Effect of adenosine on gonadotropin and prolactin secretion by hemipituitaries in vitro.

Incubation of hemipituitaries from male rats (200-220 g) with 10 nM to 1 microM adenosine induced a dose-dependent decrease of the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) into the medium, and increased prolactin (PRL) secretion. The effects of 10 nM adenosine were blocked by 100 nM caffeine, whereas 100 nM caffeine alone had no effect on the release of the hormones. Preincubation of hemipituitaries with 1 microM adenosine also inhibited 10 nM luteinizing hormone-releasing hormone (LHRH)-induced LH and FSH release by greater than 90%. These data indicate a regulatory role for adenosine in pituitary LH, FSH and PRL release, and also a possible modulatory effect of adenosine on the LHRH-LH and FSH system.

Adenosine↗

Testes alterations in pubertal benznidazole-treated rats.

To determine the side effects of benznidazole, an antiparasitic chemotherapeutic agent against chagasic infection, rats were treated with 80 mg benznidazole kg-1 day-1, p.o., for 30 days, while controls received the vehicle. Treated animals developed severe testicular atrophy (0.25 +/- 0.02 g/100 g vs 0.44 +/- 0.02 g/100 g for the controls), though plasma testosterone level, relative weight of seminal vesicles and prostate were similar to those of the controls. Histological examination of the testes revealed a statistically significant alteration in the spermatogenic process with a marked decrease in the frequency of meiosis, number of tubular sections with mature spermatids and depletion of germinal epithelium.

Animals↗

Ether and immobilization stress effects on pituitary adrenal function in hemidecorticate rats.

Hemidecortication (HD) (left cerebral hemisphere) was performed in rats with the aim of analyzing the modulating effect of the cerebral cortex on the hypothalamic-pituitary-adrenal axis. Corticosterone release induced either by ether or immobilization stress was evaluated in control (C) and HD rats. The percentage increase in corticosterone was greater in HD than in C rats after 15 min of ether stress (HD = 142%, C = 50%) and after 60 min of immobilization stress (HD = 197%, C = 126%). An in vitro test showed that the release of ACTH induced by corticotropin releasing hormone (CRH) from hemipituitary fragments from HD rats was not different from that in control rats. These results suggest an inhibitory effect of the cerebral cortex on the hypothalamus which may modulate the secretion of corticotropin releasing peptides.

Animals↗

Modulatory effects of adrenergic agonists on testosterone secretion from rat dispersed testicular cells or Percoll-purified Leydig cells.

1. Freshly dispersed testicular interstitial cells as well as Percoll-purified Leydig cells were studied in vitro in order to evaluate the effect of adrenergic agonists on testosterone (T) secretion. 2. Epinephrine and phenylephrine did not change the rate of T release under basal conditions in freshly dispersed interstitial cells, but enhanced it during human chorionic gonadotropin (hCG) stimulation. Norepinephrine and clonidine had no effect on T secretion. 3. In contrast, in Percoll-purified Leydig cells epinephrine increased T release both under basal and hCG-stimulated conditions. 4. These data demonstrate that neurotransmitters may participate in T secretion from isolated Leydig cells.

Animals↗

Characterization of adrenergic control of the Leydig cell steroidogenesis: identification of both stimulatory and inhibitory components.

Percoll-purified Leydig cells were studied in vitro in order to evaluate the effect of adrenaline on testosterone (T) secretion. Adrenaline enhanced the basal and potentiated the hCG-induced T release. A similar effect was also obtained with the beta 2-agonist, salbutamol. Although phenylephrine, an alpha 1-agonist, did not alter the basal T secretion, it enhanced hCG-mediated T secretion. Para-aminoclonidine, an alpha 2-agonist, decreased the basal T release without altering the hCG-stimulated T release. These data demonstrate that either inhibitory or stimulatory effects on T release can be obtained and that they depend on the adrenoreceptor subtype involved.

Animals↗

Role of opiates in the regulation of water and salt metabolism: effects of the FK 33-824 injection into the subfornical organ of both normal and hypophysectomized rats.

The present study was performed to evaluate the participation of the subfornical organ (SFO) in the opioid modulation of urinary volume (Uv), and of sodium and potassium excretion. Intact and hypophysectomized (HYPOX) adult male rats were implanted with a cannula into the SFO, and injected with the opiate agonist FK 33-824 (FK). FK induced a significant decrease in Uv and in Na+ and K+ excretion in both intact and HYPOX rats. The data show that opioids play an important role in the regulation of hydromineral metabolism by the SFO.

Animals↗

Evidence for a negative ultrashort loop feedback mechanism operating on the luteinizing hormone-releasing hormone neuronal system.

The present studies were designed to determine whether an ultrashort loop feedback mechanism is involved in the regulation of LHRH secretion. Daily administration of a highly potent LHRH agonist (LHRH-AGO; [D-Ala6,Des-Gly10] LHRH ethylamide) immediately after orchidectomy (ORDX) significantly attenuated the rise of plasma LH from days 2 through 10 after ORDX. Concomitantly with the diminished LH rise after ORDX, a significant increase in LHRH content in the arcuate nucleus was observed in LHRH-AGO-treated rats. Measurement of LHRH levels in hypophyseal portal blood in rats 10 days after ORDX combined with daily agonist treatment revealed a significant decrease in LHRH values in portal plasma compared with those in orchidectomized controls. Arcuate nuclei-median eminence (ME) fragments obtained from ORDX rats treated in vivo with LHRH-AGO for 5 days showed a decreased basal secretion of LHRH and a diminished response to K+ stimulation compared with the release from fragments obtained from ORDX saline-treated controls. To evaluate whether a tonic LHRH inhibitory activity operates within the ME, additional experiments were performed in which ME fragments were incubated in vitro in the presence of a potent LHRH antagonist [( D-pGlu1,D-Phe2,D-Trp3,6]LHRH). The antagonist significantly enhanced the basal secretion of LHRH in a dose-dependent manner. The latter results suggest that LHRH antagonists may enhance LHRH release, perhaps by interacting with LHRH receptors playing an inhibitory role on the endogenous secretion of the decapeptide. These observations strongly suggest a tonic inhibitory or modulatory role of LHRH neurons in the regulation of their own function.

Animals↗

Pulsatile peptide secretion: encoding of brain messages regulating endocrine and reproductive functions.

Neuropeptides are defined chemical messengers produced by the brain to modulate its own activity and also to regulate the function of every organ system. These neuropeptides can be viewed as coded chemical signals produced by the brain and secreted into the blood or into other fluids, such as the cerebrospinal fluid, to be transported and to act at a distant site. The signals arrive to the target organ or sometimes to an intermediary station, such as the pituitary gland, where they are decoded, transformed into a more powerful signal, and sent again through the general circulation to reach their final target. Our work has characterized the episodic or pulsatile pattern of secretion of a number of peptide hormones produced by the brain or the pituitary gland and analyzed the brain mechanisms involved in the generation of such a pulsatile pattern of hormone secretion. Molecular biology approaches have provided information on the synthesis, processing, and secretion of these brain messengers. In addition, using computer-assisted perifusion systems, we have been able to reproduce in vitro some of the signals produced by the brain and are currently trying to decode the message carried by those signals, as well as determining the intracellular messengers involved in the signal process. The importance of the neuropeptides and of the messages carried by the pulsatile signal is underlined by experiments in which animals treated with a neurotoxin were rendered infertile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibitory role of cholinergic agonists on testosterone secretion by purified rat Leydig cells.

The effects of cholinometics on basal or hCG-induced testosterone (T) release by Percoll-purified Leydig cells of the rat were studied. Acetylcholine and carbachol as well as nicotine decreased basal and hCG-induced T secretion. The ganglionic nicotine antagonist hexamethonium promoted a partial reversal of the inhibitory effect of nicotine on basal or hCG-stimulated T secretion. Atropine also reduced the inhibitory effect of carbachol on basal or stimulated androgen release. These data indicate that, in short-term incubations, testosterone released by purified Leydig cells is inhibited by nicotinic and muscarinic cholinergic agonists, thus supporting the hypothesis that parasympathetic autonomic system may be involved in the negative regulation of testicular androgen secretion.

Animals↗