Current preconception care practice in the Netherlands - An evaluation study among birth care professionals.

OBJECTIVE: To evaluate the current practice of preconception care in the Netherlands and the perceptions of birth care professionals concerning preconception care. METHODS: We have developed a digital questionnaire and conducted a cross-sectional study by distributing the questionnaire among 102 organisations: 90 primary care midwifery practices and obstetric departments of 12 hospitals in the Southwest region of the Netherlands between December 2020 and March 2021. One birth care professional per organization was asked to complete the questionnaire. Descriptive statistics were used to present the results. FINDINGS: Respondents of eighty-three organisations (81.4 %) filled in the questionnaire, of whom 74 respondents were independent primary care midwives and 9 respondents were obstetricians. Preconception care mostly consisted of an individual consultation in which personalized health and lifestyle advice was given. Among the respondents, 44.4 % reported that the organization had a preconception care protocol. The way in which the consultation was carried out, as well as the health and lifestyle related questions asked, differed between respondents. More than 85 % of the respondents inquire about the following possible risk factors for complications: maternal illnesses, obstetric history, folic acid supplement intake, alcohol intake, smoking, substance abuse, hereditary disease, prescription medication, dietary habits, overweight, and birth defects in the family. The respondents acknowledged that preconception care should be offered to all couples who wish to become pregnant, as opposed to offering preconception care only to those with an increased risk of complications. Still, respondents do not receive many questions regarding the preconception period or requests for preconception care consultations. KEY CONCLUSION: Birth care professionals acknowledge the need for preconception care for all couples. In the Netherlands, preconception care consists mostly of an individual consultation with recommendations for health and lifestyle advice. However, the identification of risk factors varies between birth care professionals and less than half of the respondents indicate that they have a protocol available in their practice. Furthermore, the demand of parents-to-be for preconception care is low. More research, that includes more obstetricians, is necessary to investigate if there is a difference between the care provided by primary care midwives and obstetricians. IMPLICATIONS FOR PRACTICE: To increase the awareness and uptake of preconception care, it would be prudent to emphasize its importance to parents-to-be and professionals, and actively promote the use of widespread, standardized protocols for birth care professionals.

Maternal plasma polyunsaturated fatty acid levels during pregnancy and childhood lipid and insulin levels.

BACKGROUND AND AIMS: Maternal polyunsaturated fatty acid (PUFA) levels are associated with cord blood lipid and insulin levels. Not much is known about the influence of maternal PUFAs during pregnancy on long-term offspring lipid and insulin metabolism. We examined the associations of maternal plasma n-3 and n-6 PUFA levels during pregnancy with childhood lipid and insulin levels. METHODS AND RESULTS: In a population-based prospective cohort study, among 3230 mothers and their children, we measured maternal second trimester n-3 and n-6 PUFA plasma levels. At the median age of 6.0 years (95% range, 5.6-7.9), we measured childhood total-cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, insulin and c-peptide levels. Higher maternal total n-3 PUFA levels, and specifically DHA levels, were associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels (p-values <0.05), but not with LDL-cholesterol and triglycerides. Maternal total n-6 PUFA levels were not associated with childhood outcomes, but higher levels of the individual n-6 PUFAs, EDA and DGLA were associated with a lower childhood HDL-cholesterol, and higher AA levels with higher childhood total-cholesterol and HDL-cholesterol levels (all p-values <0.05). A higher maternal n-6/n-3 PUFA ratio was only associated with lower childhood HDL-cholesterol and insulin levels (p-values <0.05). These associations were not explained by childhood body mass index. CONCLUSIONS: Higher maternal total n-3 PUFAs and specifically DHA levels during pregnancy are associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels. Only individual maternal n-6 PUFAs, not total maternal n-6 PUFA levels, tended to be associated with childhood lipid and insulin levels.

[Reflection on the psychiatric financial allocation in France]. / Réflexion sur la péréquation financière de psychiatrie en France.

For 25years work has been underway in France for the implementation of an alternative to public financing of health care. In the absence of progress, some regional health agencies are engaged in work related to the reallocation of public finances between psychiatric institutions. We propose a reflection with suggestion on the method proposed by the Provence Alpes Côte d'Azur Regional Health Agency. Without questioning the need for a reallocation of resources between psychiatric institutions, the method proposed here needs to evolve further to be applied in a legitimate and appropriate manner. There is a kind of urgency for a reallocation of resources between psychiatric institutions in France, but it implies a collective thinking and especially the definition of evaluation procedures for the selected models. These conditions are necessary to guarantee the quality of French psychiatry and equity in access to psychiatric care.

OS036. Ethnic differences in blood pressure and hypertensivecomplications during pregnancy; the generation R Study.

INTRODUCTION: Blood pressure levels during pregnancy are important risk factors for gestational hypertensive disorders. Non-pregnant women from ethnic minority groups are found to have higher blood pressure levels compared to white women. Little is known about variation in blood pressure development during pregnancy across different ethnic groups. OBJECTIVES: To investigate ethnic differences in blood pressure levels in each trimester of pregnancy and the risk of gestational hypertensive disorders and the degree to which such differences can be explained by education and lifestyle related factors. METHODS: The study included 6215 women participating in a population-based prospective cohort study from early pregnancy onwards in Rotterdam, The Netherlands. Ethnicity was assessed at enrolment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical records. Lifestyle factors included smoking, alcohol, caffeine intake, folic acid supplementation, sodium and energy intake, body mass index and maternal stress. Associations and explanatory pathways were investigated using linear and logistic regression analysis. RESULTS: Dutch pregnant women had higher systolic blood pressure levels as compared to women in other ethnic groups in each trimester of pregnancy. Compared to Dutch women, Turkish and Moroccan women had lower diastolic blood pressure levels in each trimester. These differences remained after adjusting for education and lifestyle factors. Turkish and Moroccan women had a lower risk of gestational hypertension as compared to Dutch women (OR 0.32; 95% CI: 0.18, 0.58 and OR 0.28; 95% CI: 0.14, 0.58) and Cape Verdean women had an elevated risk of preeclampsia (OR 2.22; 95% CI: 1.22, 4.07). Differences could not be explained by education or lifestyle. CONCLUSION: Substantial ethnic differences were observed in blood pressure levels in each trimester of pregnancy and risk of gestational hypertensive disorders. A wide range of potential explanatory variables could not explain these differences.

Interplay between galanin and leptin in the hypothalamic control of feeding via corticotropin-releasing hormone and neuropeptide Y.

Over long periods, feeding and metabolism are tightly regulated at the central level. The total amount of nutrients ingested is thought to result from a delicate balance between orexigenic and anorexigenic factors expressed and secreted by specialized hypothalamic neuronal populations. We have developed a system of perifused hypothalamic neurons to characterize the relationships existing between the orexigenic peptide galanin and two other physiological modulators of feeding: neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH). We demonstrated that galanin stimulates CRH and NPY secretion from hypothalamic neurons in a dose-dependent manner. Exposure to leptin for 24 h before galanin stimulation decreased NPY secretion by 30%, leaving the responsiveness of CRH neurons intact. These results suggest that CRH and NPY neurons participate to the intrahypothalamic signaling pathway of galanin, an observation that can explain the lower potency of galanin to stimulate food intake in vivo compared with NPY. The differential effects exerted by leptin on CRH and NPY suggest that there exists a subset of NPY neurons that are exquisitely sensitive to marked variations in leptin levels, and that the CRH neurons are less responsive to increases in leptin concentrations.

Interaction between the hypothalamo-pituitary-adrenal axis and the immunological system.

The endocrine and immune systems are interrelated via a bidirectional network in which hormones affect immune function and, in turn, immune responses are reflected in neuroendocrine changes. This bidirectional communication is possible because both systems share a common "chemical language" that results from a sharing of common ligands (hormones and cytokines) and their specific receptors. Cytokines are important partners in this crosstalk. They play a role in modulating the hypothalamo-pituitary-adrenal (HPA) axis responses at all three levels: the hypothalamus, the pituitary gland and the adrenals. Acute effects of cytokines are produced at the central nervous system level, particularly the hypothalamus, whereas pituitary and adrenal actions are slower and are probably involved during prolonged exposure to cytokines such as during chronic inflammation or infection. Several mechanisms have been proposed by which peripheral cytokines may gain access to the brain. They include an active transport through the blood-brain barrier, a passage at the circumventricular organ level, as well as a neuronal pathway through the vagal nerve. The immune-neuroendocrine interactions are involved in numerous physiological and pathophysiological conditions and the interactions with the HPA axis may represent a mechanism through which the immune system, by stimulating the production of glucocorticoids, avoids an overshoot of inflammatory response. The crosstalk between the immune and endocrine systems is important to homeostasis, since the interactions can produce various appropriate adaptative responses when homeostasis is threatened.

Acceleration of pubertal development following central blockade of the Y1 subtype of neuropeptide Y receptors.

Pubertal development results from the coordinate secretion of gonadotropin-releasing hormone (GnRH) by hypothalamic GnRH neurons. Central administration of neuropeptide Y (NPY) to prepubertal rats can indefinitely delay sexual maturation by inhibiting this GnRH secretion. The aim of the present study was to further investigate the physiological role of NPY in pubertal development, and to assess the potential involvement of its Y1 receptor subtype in this setting. The timing of pubertal development was determined in juvenile female rats receiving chronic i.c.v. infusion of a specific Y1 receptor antagonist (BIBP 3226), and compared with controls. Although treatment with BIBP 3226 did not affect the age at vaginal opening, animals receiving the Y1 antagonist experienced a quicker progression through puberty, corroborated by a significant increase in pituitary luteinizing hormone content. This effect of BIBP3226 on the gonadotrope axis occurred without apparent toxicity, but was accompanied by a transient decrease in body weight gain on the first day of treatment, suggesting an effect on appetite. Together, our results add to the evidence in favour of a role for NPY in the onset of puberty. They are entirely consistent with the proposed inhibition exerted by endogenous hypothalamic NPY before the onset of pubertal development. They also suggest that the Y1 subtype of NPY receptors is involved in this effect.

A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: determination of different sites of action.

Immune neuroendocrine interactions are vital for the individual's survival in certain physiopathological conditions, such as sepsis and tissular injury. It is known that several animal venoms, such as those from different snakes, are potent neurotoxic compounds and that their main component is a specific phospholipase A type 2 (PLA2). It has been described recently that the venom from Crotalus durissus terrificus [snake venom (SV), in the present study] possesses some cytotoxic effect in different in vitro and in vivo animal models. In the present study, we investigated whether SV and its main component, PLA2 (obtained from the same source), are able to stimulate both immune and neuroendocrine functions in mice, thus characterizing this type of neurotoxic shock. For this purpose, several in vivo and in vitro designs were used to further determine the sites of action of SV-PLA2 on the hypothalamo-pituitary-adrenal (HPA) axis function and on the release of the pathognomonic cytokine, tumor necrosis factor alpha (TNF alpha), of different types of inflammatory stress. Our results indicate that SV (25 microg/animal) and PLA2 (5 microg/animal), from the same origin, stimulate the HPA and immune axes when administered (i.p.) to adult mice; both preparations were able to enhance plasma glucose, ACTH, corticosterone (B), and TNF alpha plasma levels in a time-related fashion. SV was found to activate CRH- and arginine vasopressin-ergic functions in vivo and, in vitro, SV and PLA2 induced a concentration-related (0.05-10 microg/ml) effect on the release of both neuropeptides. SV also was effective in changing anterior pituitary ACTH and adrenal B contents, also in a time-dependent fashion. Direct effects of SV and PLA2 on anterior pituitary ACTH secretion also were found to function in a concentration-related fashion (0.001-1 microg/ml), and the direct corticotropin-releasing activity of PLA2 was additive to those of CRH and arginine vasopressin; the corticotropin-releasing activity of both SV and PLA2 were partially reversed by the specific PLA2 inhibitor, manoalide. On the other hand, neither preparation was able to directly modify spontaneous and ACTH-stimulated adrenal B output. The stimulatory effect of SV and PLA2 on in vivo TNF alpha release was confirmed by in vitro experiments on peripheral mononuclear cells; in fact, both PLA2 (0.001-1 microg/ml) and SV (0.1-10 microg/ml), as well as concavalin A (1-100 microg/ml), were able to stimulate TNF alpha output in the incubation medium. Our results clearly indicate that PLA2-dependent mechanisms are responsible for several symptoms of inflammatory stress induced during neurotoxemia. In fact, we found that this particular PLA2-related SV is able to stimulate both HPA axis and immune functions during the acute phase response of the inflammatory processes.

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia.

Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4-6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system.

Increased vasopressinergic activity as a possible compensatory mechanism for a normal hypothalamic-pituitary-adrenal axis response to stress in BALB/c nude mice.

A bidirectional relationship between the immune and neuroendocrine systems is now widely accepted. Since it is well known that the thymus plays an important role in the regulation of the immune function, we decided to explore whether a lack of the thymic function may influence hypothalamic-pituitary-adrenal (HPA) axis activity. Eight-week-old female mice of both strains, nude and control BALB/c, were used to study: (a) the in vivo response of the HPA axis to several stress stimuli acting at either the hypothalamic (insulin administration and ether vapor inhalation), pituitary (CRH and vasopressin injections) or adrenal (ACTH treatment) level and (b) the in vitro response of hypothalamic fragments to high KCl (48 mM) stimulation. The results indicate that: (1) basal plasma ACTH and vasopressin levels were significantly (p < 0.05) higher in nude than in control BALB/c mice, whereas basal plasma corticosterone concentrations were similar in both strains of mice; (2) although no significant strain-related difference in the stress-induced ACTH secretion in plasma was found, hypothalamic stimuli were able to induce a significantly (p < 0.05) higher secretion of glucocorticoid in plasma in nude than in control BALB/c mice; (3) the pattern of in vitro hypothalamic CRH release was similar in both strains of animals; however, basal AVP output and that stimulated by 48 mM KCl were significantly (p < 0.05) higher in nude than in control hypothalamic fragments, and (4) whereas hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid contents were similar in both strains, hypothalamic AVP content was significantly (p < 0.05) higher in athymic than in control mice. In summary, our results indicate that nude mice have an increased vasopressinergic function which could contribute to a normal HPA axis activity; thus, adult athymic mice of BALB/c origin could compensate, due to their increased vasopressinergic function, for a robust glucocorticoid release to protect themselves immediately after aggression. It remains to be determined whether this enhanced vasopressinergic function is a result of an early adrenal insufficiency due to congenital deficiency of thymic factors known to stimulate HPA axis function.

Sex and strain variability in the rat hypothalamo-pituitary-adrenal (HPA) axis function.

In the present investigation, we examined the influence of both genetic background and sex factors in the rat hypothalamo-pituitary-adrenal (HPA) axis function under both basal and post adrenalectomy (ADX) conditions. For these purposes adult female and male rats, from Sprague-Dawley (S-D), Fischer (F344/N), Lewis (LEW/N) and Buffalo (BUF) strains, were decapitated in basal condition or several (2, 7 and 14) days after ADX. Plasma stress hormones levels and adrenal corticosterone (B) concentration as well as peptide (ACTH, CRH and vasopressin, AVP) content in different tissues (anterior pituitary, AP; medial basal hypothalamus, MBH), were then evaluated by specific assays. Our results indicate that: a) despite no sex- and strain-related differences in AP ACTH and MBH ACTH secretagogues in basal condition, there exits a clear sexual dimorphism in plasma ACTH levels as well as in both plasma and adrenal B concentrations, with values significantly higher in females than in males, regardless the strain; b) ADX abolished plasma B levels and increased AP ACTH output in a time-dependent fashion up to the 14th day post surgery; c) AP ACTH content decreased 2 days after ADX, except in BUF female rats, thereafter tending to either recover or increase sham values by two weeks post ADX; d) ADX decreased MBH CRH at all periods studied, except in BUF female animals on day 14; e) ADX clearly diminished MBH AVP only in S-D rats, and f) a sexual dimorphism was also found in AP ACTH in 7-day-ADX S-D rats and in 14-day-ADX S-D and F344/N animals; also, a dimorphic pattern in MBH CRH was found in 7-day-ADX S-D as well as in 14-day-ADX F344/N and LEW/N rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of chronic glucocorticoid excess, adrenalectomy and stress on neuropeptide Y in individual rat hypothalamic nuclei.

Several lines of evidence indicate a role for neuropeptide Y (NPY) in the modulation of the corticotroph axis. In two separate studies reported here, the concentrations of NPY and noradrenaline (NA), as well as corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), were measured in extracts of individual rat hypothalamic nuclei after various manipulations producing either a state of chronic glucocorticoid excess or depletion, and also following repeated restraint stress. Alterations induced in the activity of hypothalamic neurones were inferred from the respective changes in these concentrations. 12 days after bilateral adrenalectomy (ADX), NPY levels were decreased by 24% in the arcuate nucleus (ARC) and 23% in the paraventricular nucleus (PVN, p < 0.05 vs controls). Forced immobilization of the animals for 4 h each day for 9 consecutive days (repeated stress) also decreased NPY content of the ARC by 25% (p < 0.01 vs controls), an effect blocked by the administration of glucocorticoids. NA levels in both hypothalamic nuclei were unaffected by repeated stress or ADX. Administration of glucocorticoids in the first of these studies induced decreases in NA levels by 15% and 25% in the ARC and PVN respectively (p < 0.05 vs controls). However, in subsequent experiments no significant effect of glucocorticoids on NA was observed. Our results demonstrate that the activity of the hypothalamic NPY-ergic neurones is modulated by glucocorticoids and by chronic stress. They also suggest that brainstem catecholaminergic and hypothalamic NPY-ergic neurones are differentially affected by altered glucocorticoid concentrations or by chronic stress, possibly in a stimulus-specific way.

[Music during gastroscopy]. / Musik bei der Gastroskopie.

As part of a project "Music therapy in internal medicine" we investigated 32 consecutive patients undergoing gastroscopy for various reasons. Patients were randomly assigned to two groups, regardless of sex, age or underlying disease. One group listened to music during gastroscopy, while the other did not. The choice of the type of music within the corresponding group was made with the patient and a trained music therapist in a short discussion prior to gastroscopy. The hormones ACTH and cortisol, as well as the catecholamines adrenalin and noradrenaline, were measured in both groups with three blood samples taken before, directly after and one hour after gastroscopy. Parallel measurements included blood pressure and pulse rate as well as questions about the patients' feelings during gastroscopy. The study showed the rise in the plasma levels of the stress hormones ACTH and cortisol to be significantly lower under the influence of music. The subjective feelings of the patients concerning "fear in general" and "fear about gastroscopy" paralleled these findings. Conversely, the plasma adrenalin and noradrenaline levels before and after gastroscopy were virtually unchanged in both groups, as were pulse rate and blood pressure. This study shows the influence of music on human biochemical parameters when used in the setting of a diagnostic procedure.

A tissue culture model of the hypophysiotrophic CRF producing neuronal system.

To investigate functional and chemical properties of anatomically characterized corticotropin-releasing factor-41 (CRF-41) producing neurons in vitro, hypothalamic slices of 6-day-old rats were maintained in culture for up to 6 weeks using a modified roller culture technique. This technique yields thick (100 microns) slices that contained an average of 300-400 CRF-41-immunostained neurons. The majority of CRF-41-positive cells were of small size (12-15 microns in diameter), and contained CRF-41-labeled dense core vesicles of 100 nm diameter as detected by electron microscopic postembedding immunocytochemistry. These cells represented the only CRF-41-positive cell population in the culture. Light microscope double immunolabelling of colchicine-treated cultures kept in a serum-containing media (SCM) indicated that about 60% of these CRF-41-positive neurons contains detectable levels of vasopressin-associated neurophysin (VP-NP). Culturing slices in serum-free, chemically defined media (SFM) resulted in an increased VP-NP immunostaining: parvicellular neurons labeled for both CRF-41 and VP-NP could be detected without colchicine treatment, and practically all CRF-41-positive neurons expressed VP-NP immunoreactivity. At the electron microscopic level there was a significant increase in VP-NP labeling density in the dense core vesicle compartment of CRF-41-positive varicosities. Adding dexamethasone (10 nM) to the SFM restored the staining pattern originally observed in SCM. Hence, the increased VP-NP and CRF-41 immunostaining after culturing CRF-41 neurons in SFM is most likely due to the absence of inhibitory glucocorticoids. The capacity of cultured paraventricular cells to release CRF-41 was assessed using an immunoassay. Unstimulated (basal) secretion of CRF-41 was not altered by five successive samplings at 2-hour intervals and stimulation of the same culture with 56 mmol K+ significantly increased (2-3 times) the CRF-41 content in the medium. The presence of dexamethasone (10 nM) in SFM induced a 6-fold reduction of K(+)-stimulated CRF-41 release and a 5 times reduction in tissue content in relation to cultures maintained in SFM without dexamethasone. In summary, we have demonstrated that cultured CRF-41 cells display morphological and biochemical features, as well as responsiveness to glucocorticoids, that is reminiscent to the situation in vivo. Thus, the model is well suited for studies of hypophysiotrophic CRF-41 cell functions.

Central and peripheral effects of repeated stress and high NaCl diet on neuropeptide Y.

This study was performed to investigate the influence of repeated psychological stress alone or combined with high NaCl intake on the function of the sympathetic nervous system. In addition, NPY levels have been measured in brain regions of potential importance in the central regulation of stress responses (ventrolateral and dorsomedial medulla, paraventricular and arcuate nucleus of the hypothalamus, and frontal cortex). Normotensive Wistar rats received a standard diet alone or supplemented with NaCl. To accentuate differences in sodium balance, rats on the high NaCl diet (HNa) were uninephrectomized. Half the animals on each diet were subjected to chronic stress using daily sessions (1 h) of immobilization stress. After 12 days, plasma levels of neuropeptide Y (NPY), norepinephrine (NE), and epinephrine (E) were measured basally and in response to acute footshock stress. HNa intake or chronic stress alone did not significantly alter either basal or stimulated plasma levels of NPY. However, combining the treatments produced a significant interaction, increasing the NPY response to footshock by 31% compared to HNa alone (p = 0.039) and by 98% compared to stress alone (p less than 0.001). Chronic stress increased basal levels of NE and enhanced the response to subsequent acute stress: combining the treatments did not yield further increases. Plasma levels of E were not significantly affected by the treatments. In the brain, stress alone had no effect on the NPY levels in the structures studied. HNa intake induced a significant increase in NPY levels of the arcuate nucleus, and produced a significant interaction with stress in the dorsomedial medulla. In a supplementary experiment, to evaluate the role of the autonomic nervous system in plasma NPY responses, treatment with the ganglion blocker hexamethonium was shown to significantly attenuate stress-induced changes in NPY, NE, and E.

Cytokines stimulate the CRH but not the vasopressin neuronal system: evidence for a median eminence site of interleukin-6 action.

Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10(-10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related changes in cortico-releasing factor, somatostatin, neuropeptide Y, methionine enkephalin and beta-endorphin in specific rat brain areas.

We investigated the age-related changes in the tissular protein, cortico-releasing factor (CRF), somatostatin (SOM), neuropeptide Y(NPY), methionine enkephalin (M-ENK) and beta-endorphin (beta-END) levels in frontal cortex, hippocampus, striatum and hypothalamus of young (4-month-old), mature (18-month-old) and senescent (26-month-old) Wistar male rats, bred in a specific pathogen free environment. Between the age of 4 and 18 months, the tissular protein levels increased in all 4 structures studied. The CRF and SOM levels increased in the hippocampus, while the NPY levels decreased. During this time, the NPY content increased in the striatum, whereas the SOM and M-Enk striatal levels decreased. Concomitantly, the NPY and beta-End levels decreased in the hypothalamus. Interestingly, no significant variations were found to occur in the frontal cortex whatever the neuropeptide studied. Between the age of 18 and 26 months, no significant changes in the tissular protein levels were detected, except in the hippocampus. The changes in the neuropeptide concentrations observed during this period depended on the neuropeptide and the brain structure studied. The CRF and beta-End levels decreased in the frontal cortex and the hypothalamus, respectively. The NPY peptidergic systems seem to be preferentially affected by aging processes since 3 out of the 4 structures studied--the frontal cortex, the striatum and the hypothalamus--showed a decrease in their tissular NPY content. During the same period, none of the 5 neuropeptides studied were affected in the hippocampus.

Immunohistochemical detection of proluteinizing hormone-releasing hormone peptides in neurons in the human hypothalamus.

To determine the presence of LHRH prohormone products in the human hypothalamus, antisera raised against LHRH and GnRH-associated peptide (GAP) were used to search for the presence of the corresponding antigens in the human adult and fetal hypothalamus by an immunohistochemical approach. The comparison of immunostaining on adjacent sections shows that all of the cells labeled with LHRH antiserum are also labeled with GAP antiserum and vice versa. Labeled cells are detectable during the 9th week of fetal life, this being the earliest time evaluated. At this time, the LHRH/GAP-positive cells frequently have a neuroblastic appearance. The first detectable fibers appear during the 11th week, and these were observed in the lamina terminalis cinerea and median eminence. In the adult brain, fibers and endings labeled with LHRH or GAP antiserum in the median eminence demonstrate the same topography and morphological characteristics, which are distinct from fibers labeled with other neuropeptide antisera. These results show that the LHRH precursor molecule is produced throughout life in the human hypothalamus, including the earliest stages of development of the peptidergic neurons. Moreover, the detection of LHRH- and GAP-positive fibers in the median eminence by the 11th week of fetal life suggests the possibility of an early role of LHRH and, possibly, other LHRH prohormone-derived peptides in the development of anterior pituitary function during the fetal period.

Stimulation of the hypothalamo-pituitary-adrenocortical axis by the central serotonergic pathway: involvement of endogenous corticotropin-releasing hormone but not vasopressin.

Many reports indicate that serotonin plays a role in the regulation of the hypothalamo-pituitary-adrenocortical axis. The present study was designed to elucidate whether the activation of the central serotonergic pathway enhances adrenocorticotropin and corticosterone secretion, and if so, whether the CRH and vasopressin neuronal systems could be mediating this effect. Intraperitoneal administration of a low dose of L-5-hydroxytryptophan (an aromatic L-amino acid precursor of serotonin synthesis; 20 mg/kg bw, 30 minutes before the sacrifice) in rats pretreated with pargyline (a brain monoamine oxidase inhibitor, which enhances monoamine activity; 75 mg/Kg bw, 16 hours before the sacrifice) and carbidopa (a peripheral active inhibitor of the decarboxylation of aromatic L-amino acids, which would permit more monoamine precursor to be available to the brain; 50 mg/Kg bw, 90 minutes before the sacrifice) increased ACTH and corticosterone secretion in plasma. Such an effect was partially blocked by metergoline (a serotonin type-1 and-2 receptor blocker; 1 mg/Kg bw, 90 minutes before the sacrifice), but not by spiperone (a serotonin type-2 and dopamine receptor antagonist; 0.5 mg/Kg bw. 90 minutes before the sacrifice). The activation of the central serotonergic system enhanced the CRH content in the median eminence, whereas it decreased the content of this neuropeptide in the medial basal hypothalamus. These effects were fully abolished by metergoline, but not by spiperone pretreatment. The activation of the serotonergic pathway did not influence the vasopressinergic neuronal system. In vitro experiments using hypothalamic-median eminence fragments incubated with serotonin solutions indicate that this monoamine possesses a CRH releasing effect at concentrations of 1 microM or more.(ABSTRACT TRUNCATED AT 250 WORDS)