La separación materna durante la lactancia altera los niveles basales del sistema neuroendocrino en ratas adolescentes y adultas / Maternal separation during nursing alters basal neuroendocrine levels in juvenile and adult rats

Introducción. En diversos modelos animales, incluido el de la separación materna durante la lactancia, se ha demostrado que las experiencias tempranas adversas, como el maltrato, el abandono materno y el estrés psicosocial, pueden favorecer el desarrollo de algunas enfermedades mentales, pero no se han descrito completamente varios de los cambios que se producen en el sistema neuroendocrino. Objetivo. Determinar si la separación materna durante la lactancia modificaba los niveles basales de neurohormonas como la corticosterona, la corticotropina (ACTH), la oxitocina y la vasopresina (ADH), en ratas jóvenes (35 días) y adultas (90 días). Materiales y métodos. Se separaron ratas Wistar de sus madres durante dos periodos de tres horas diarias a lo largo de los 21 días de lactancia. A los 35 y 90 días se tomaron muestras de los grupos de las ratas de control y de las separadas de la madre, para obtener el suero y posteriormente medir cada una de las hormonas mediante un ensayo inmunoenzimático. Resultados. Las concentraciones de corticosterona fueron mayores en las hembras adultas de control que en el resto de los grupos, y menores en los machos adultos de control. Las de ACTH fueron mayores en los machos y hembras jóvenes separadas de la madre que en los grupos de adultos. Los niveles de oxitocina fueron significativamente mayores en las hembras adultas separadas de la madre que en los otros grupos y significativamente menores en los machos adultos. En cuanto a la vasopresina, los grupos separados de la madre tuvieron concentraciones menores, en comparación con los grupos de jóvenes y adultos de control. Conclusiones. Estos resultados muestran que el estrés temprano al que fueron sometidas las ratas, produjo cambios en las respuestas del eje hipotálamo-hipófisis-suprarrenal, las cuales variaron según el sexo y la edad.

Introduction: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. Objective: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). Materials and methods: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. Results: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. Conclusions: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.

Métodos de indução do trabalho de parto / Methods of induction of labour

Os métodos de indução do parto podem ser divididos em estímulos naturais, estímulos exógenos diretos ou mecânicos e estímulos exógenos indiretos ou farmacológicos, cada qual apresenta suas particularidades nas indicações e contraindicações. O objetivo deste artigo foi realizar uma revisão da literatura consultando Medline/Pubmed e a Biblioteca Cochrane para avaliar a eficácia e segurança na utilização dos principais métodos de indução do trabalho de parto. Apurou-se não haver método ideal de indução do trabalho de parto. Os estímulos naturais e os métodos alternativos carecem de maiores estudos para incentivo de seu uso rotineiro. As prostaglandinas, em destaque o misoprostol, está indicada no Índice de Bishop desfavorável e a ocitocina em condições cervicais favoráveis. Os avanços no campo da biologia molecular tem corroborado que o método ideal deve atuar em sincronismo com a contratilidade uterina e a maturação cervical.(AU)

Methods of labor induction can be classified as natural stimuli, direct exogenous stimuli or mechanical and indirect exogenous stimuli or pharmacological. Which one has its peculiarities in relation to indications and contraindications. The objective of this article was to assess the efficacy and safety of the main methods of induction of labor trough the analysis of the medical literature in Medline/Pubmed and the Cochrane Library to. No ideal method of inducing labor was found. Further studies are required to encourage natural stimuli and alternative methods more often. According to Bishop scores, prostaglandins, (especially misoprostol) are unfavorable and oxytocin in case of favorable cervical environment. Advances in the field of molecular biology have confirmed that the ideal method should work simultaneously with uterine contraction and cervical ripening.(AU)

Oxitocina, vasopresina y conducta social: hipótesis neuropéptida para el trastorno autista / Oxytocin, vasopressin and social behavior: neuropeptide hypothesis

Introducción: El Trastorno Autista es una patología de inicio temprano que evoluciona hacia la cronicidad y se caracteriza principalmente por un desarrollo marcadamente anormal o deficiente de la interacción y comunicación social. Es más frecuente en hombres y si bien se presume que es de origen multifactorial, se plantea que puede ser explicado, al menos en parte, por una alteración en la neurobiología que da sustento a las conductas sociales normales. La Oxitocina y la Vasopresina han sido ampliamente relacionadas con las conductas sociales tanto en animales como en humanos, específicamente han sido relacionadas con las conductas de apego, de filiación y con el Trastorno Autista. Objetivos: Entregar un marco teórico que contribuya a organizar el amplio conocimiento que existe sobre la fisiopatología del Trastorno Autista y que entregue luces tanto para la investigación como para la clínica. Método: Se realiza una revisión bibliográfica sobre el rol que juegan la Oxitocina y la Vasopresina en las conductas sociales sanas y anormales tanto en animales como en humanos centrándose la discusión en la relación que tienen estos neuropéptidos con el Trastorno Autista. Conclusiones: Si bien se presume que la fisiopatología del Trastorno Autista es de origen multifactorial, se logra organizar un marco teórico para la comprensión de la fisiopatología del trastorno desde una hipótesis neuropéptida, lo cual tiene implicancias tanto para la investigación como para la clínica.

Introduction: Autistic disorder is an early onset disease that evolves into chronicity, characterized by the presence of markedly abnormal or deficient development of social interaction and communication. It is more common in men and although presumed to be of multifactorial origin, it is proposed that it can be explained, at least in part, by alterations in the neurobiology which gives supports to normal social behavior. Oxytocin and vasopressin have been widely associated with social behavior in animals and humans, specifically with attachment behaviors, affiliation and Autistic Disorder. Objectives: To provide a theoretical framework in order to help organize the extensive knowledge that exists about the pathophysiology of autistic disorder and to deliver light for both research and clinic. Methods: We performed a systematic review of the role played by oxytocin and vasopressin in healthy and abnormal social behavior in both animals and humans and focused the discussion on the relationship that have these neuropeptides with Autistic Disorder. Conclusions: Understanding the pathophysiology of the Autistic Disorder from a neuropeptide hypothesis, provides a theorethical framework which has implications for both research and clinic.

Organotypic slice culture of the hypothalamic paraventricular nucleus of rat

Organotypic slice cultures have been developed as an alternative to acute brain slices because the neuronal viability and synaptic connectivity in these cultures can be preserved well for a prolonged period of time. This study evaluated a stationary organotypic slice culture developed for the hypothalamic paraventricular nucleus (PVN) of rat. The results showed that the slice cultures maintain the typical shape of the nucleus, the immunocytochemical signals for oxytocin, vasopressin, and corticotropin-releasing hormone, and the electrophysiological properties of PVN neurons for up to 3 weeks in vitro. The PVN neurons in the culture expressed the green fluorescent protein gene that had been delivered by the adenoviral vectors. The results indicate that the cultured slices preserve the properties of the PVN neurons, and can be used in longterm studies on these neurons in vitro.

Social stimuli cause changes of plasma oxytocin and behavior in guinea pigs

The neuropeptide oxytocin (OXT) is a key factor in the initiation and regulation of sociosexual behavior. The present study analyzes the effects of cohabitation and social challenge on plasma OXT concentration rates in guinea pig pairs in relation to male sociosexual behavior. The cohabitation phase lasted 3 days. On day 4, the pair was socially challenged by introducing an unfamiliar male. Displayed male sexual behavior varied significantly during cohabitation, with peaks on day 1. Sociopositive behavior, i.e., side-by-side contact, was increased on days 3 and 4. Cohabitation per se led to elevated plasma OXT concentrations only in males. In contrast, both sexes reacted with increased plasma OXT concentrations to the social challenge (day 4). At that time, male OXT was significantly correlated with sexual behavior and female OXT with sociosexual behavior received from the partner. Additionally, pairs were synchronized in their OXT release during days 3 and 4. We conclude that cohabitation causes sexually dimorphic plasma OXT concentration patterns in guinea pigs. Secondly, the conformity of OXT release in both sexes may represent an endocrine marker for long-term cohabitation, which is reflected behaviorally by increased spatial proximity.

Uterine mast cells: a new hypothesis to understand how we are born

Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review.

Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

The release of adrenocorticotropin (ACTH) from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH). Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC) in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

Angiotensin-(1-7) increases osmotic water permeability in isolated toad skin

Angiotensin-(1-7) (Ang-(1-7)) increased osmotic water permeability in the isolated toad skin, a tissue with functional properties similar to those of the distal mammalian nephron. Concentrations of 0.1 to 10 ÁM were effective, with a peak at 20 min. This effect was similar in magnitude to that of frog skin angiotensin II (Ang II) and oxytocin but lower than that of human Ang II and arginine-vasotocin. The AT2 angiotensin receptor antagonist PD 123319 (1.0 ÁM) fully inhibited the response to 0.1 ÁM Ang-(1-7) but had no effect on the response to Ang II at the same concentration. The specific receptor antagonist of Ang-(1-7), A-779, was ineffective in blocking the response to Ang-(1-7) and to frog skin Ang II. The AT1 receptor subtype antagonist losartan, which blocked the response to frog skin Ang II, was ineffective in blocking the response to Ang-(1-7). The present results support the view of an antidiuretic action of Ang-(1-7) in the mammalian nephron

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

Interaction between NO and oxytocin: influence on LHRH release

Nitric oxide synthase (NOS)-containing neurons have been localized in various parts of the CNS. These neurons occur in the hypothalamus, mostly in the paraventricular and supraoptic nuclei and their axons project to the neural lobe of the pituitary gland. We have found that nitric oxide (NO) controls luteinizing hormone-releasing hormone (LHRH) release from the hypothalamus acting as a signal transducer in norepinephrine (NE)-induced LHRH release. LHRH not only releases LH from the pituitary but also induces sexual behavior.On the other hand, it is known that oxytocin also stimulates mating behavior and there is some evidence that oxytocin can increase NE release. Therefore, it occurred to us that oxytocin may also stimulate LHRH releave via NE and NO. To test this hypothesis, we incubated medial basal hypothalamic (MBH) explants from adult male rats in vitro. Following a preincubation period of 30 min, MBH fragments were incubated in Krebs-Ringer bicarbonate buffer in the presence of various concentrations of oxytocin. Oxytocin relesed LHRH at concentrations ranging from 0.1 nM to 1muM with a maximal stimulatory effect (P<0.001) at 0.1 muM, but with no stimulatory effect at 10 muM. That these effects were mediated by NO was shown by the fact that incubation of the tissues with NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, blocked the stimulatory effects. Furthermore, the release of LHRH by oxytocin was also blocked by prazocin, an alpha1-adrenergic receptor antagonist, indicating that NE mediated this effect. Oxytocin at the same concentrations also increased the activity of NOS (P<0.01) as measured by the conversion of [14C]arginine to citrulline, which is produced in equimolar amounts with NO by the action of NOS. The release of LHRH induced by oxytocin was also accompanied by a significant (P<0.02) increase in the release of prostaglandin E2 (PGE2), a mediator of LHRH release that is released by NO. On the other hand, incubation of neural lobes with vaious concentrations of sodium nitroprusside (NP) (300 or 600 muM), a releaser of NO, revealed that NO acts to suppres (P<0.01) the release of oxytoxin. Therefore, our results indicate that oxytocin releases LHRH by stimulating NOS via NE, resulting in an increased release of NO, which increases PGE2 release that in turn induces LHRH release. Furthermore, the released NO can act back on oxytocinergic terminals to suppress the release of oxytocin in an ultrashort-loop negative feedback.

Gossypol affects the responsiveness of isolated rat myometrium and vas deferens

The effects of gossypol on responsiveness of both rat myometrium and vas deferens were analyzed. In myometrial strips, gossypol (1-30 micronM) produced rightward displacemtns of the cumulative concentration-response curves to acetylcholine, bradykinin and oxytocin, accompanied by reductions in maximal responses. Gossypol (30 micronM) also completely abolished the contractions induced by field stimulation of the rat vas deferens. The IC50 values for gossypol against agonist-uinduced myometrial contractions and field-stimulated vas deferens contractions were similar, ranging between 13 and 18 micronM. These results provide additional evidence that gossypol exerts a direct and irreversible inhibition of the contractility of both male and female reproductive organs

Depuracion miometral de la oxitocina exogena en la hipertension arterial inducida por el embarazo / Miometrial depuration of exogenus oxytocin in induced arterial hypertension by pregnancy

La vida media uterina (VMU) de la oxitocina exogena se acepta como una medida indirecta de la vida media plasmatica de la hormona y por tanto, de su depuracion. Hasta el momento no se ha estudiado la VMU en embarazos patologicos. Este trabajo comunica las primeras medidas de la VMU en pacientes con hipertension arterial inducida por el embarazo, clasificada como pre-eclampsia severa. Los valores promedio fueron para el grupo control, 15.1 minutos; y para los casos estudiados, 25.8 minutos. Estos valores permiten calcular una vida media plasmatica aumentada casi al doble en la pre-eclampsia severa. Se discute la fisiopatologia de este hallazgo y se sugiere un posible disturbio metabolico originado en una disminucion de la depuracion renal de la oxitocina

Problems Associated with I-125 Oxytocin Binding to Membrane Receptors

Radioiodinated oxytocin prepared by the lactoperoxidase method exhibited a substantial biologic activity in uterotonic assay of the rat uterus. 125I-oxytocin was bound to the uterine membrane particulate fraction, but the unlabelled oxytocin did not inhibit the binding of 125I oxytocin to the membrane fraction of rat uterus. Cold iodinated oxytocin, however, inhibited the 125I-oxytocin binding to the membrane fraction of rat uterus in proportion to its concentration. These results suggest that 125I-oxytocin is not a suitable radioligand for oxytocin receptor binding study.