Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women

Aims/hypothesis: Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFß1, confer high risk of pre-eclampsia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in pre-eclampsia.
Methods: Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term.
Results: Approximately 22% of the diabetic women developed pre-eclampsia, primarily after their third trimester visit. In women with pre-eclampsia (diabetic pre-eclampsia, n?=?26) vs those without hypertensive complications (diabetic normotensive, n?=?95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of pre-eclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-eclampsia vs type 1 diabetic normotensive women at the third trimester visit (p?<?0.05) and the normal rise of PlGF during pregnancy was blunted (p?<?0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r2?=?42%, p?<?0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (p?<?0.0001).
Conclusions/interpretation: Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of pre-eclampsia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-eclampsia and may contribute to the high incidence of pre-eclampsia in this patient group.

Polymorphisms at the five exons of gowth hormone gene in the Algarvia Goat. Possible association with milk traits

The present preliminary study attempts to establish associations between milk production traits and genetic polymorphisms at the GH gene in the Algarvia goat. The DNA of 108 goats of the indigenous Portuguese Algarvia breed was evaluated.

Do princípio da boa fé nos contratos de seguro

O objetivo deste estudo foi analisar os seguintes tópicos: a possibilidade de interpretação literal do artigo 798 do Código Civil brasileiro, a aplicação das súmulas 61 e 105 do STF, o cabimento de indenização à família do suicida, os entendimentos da neurociência sobre possibilidades que podem interferir na ideação suicida, a visão e, finalmente, posicionamentos do Superior Tribunal de Justiça (STJ) e do Supremo Tribunal Federal do Brasil e quanto ao pagamento da indenização estabelecido no contrato de seguro de vida em caso de suicídio do contratante antes dos dois anos da assinatura do contrato. Buscou-se, também, comparar a doutrina e jurisprudência do Brasil e de Portugal. Na estrutura, iniciou-se por considerações sobre a interpretação jurídica e, em seguida, foram desenvolvidos os capítulos acerca de negócio jurídico, dos contratos, dos contratos de seguro de vida e da boa fé presente e necessária. Como o foco principal eram os contratos de seguro de vida e baseando-se na doutrina e na jurisprudência, de modo geral, mesmo a legislação dos dois países diferindo em pequenos aspectos, concluiu-se que: (1) o seguro é a cobertura de evento futuro e incerto que poderá gerar o dever de indenizar por parte do segurador; (2) a boa-fé - que é presumida - constitui elemento intrínseco do seguro, e é caracterizada pela lealdade nas informações prestadas pelo segurado ao garantidor do risco pactuado; (3) o legislador procurou evitar fraudes contra as seguradoras na hipótese de contratação de seguro de vida por pessoas que já tinham a idéia de suicídio quando firmaram o instrumento contratual; (4) uma coisa é a contratação causada pela premeditação ao suicídio, que pode excluir a indenização. Outra, diferente, é a premeditação para o próprio ato suicida;(5) é possível a interpretação entre os enunciados das Súmulas 105 do STF e 61 da Corte Superior na vigência do Código Civil de 2002; e (6) as regras relativas aos contratos de seguro devem ser interpretadas sempre com base nos princípios da boa fé e da lealdade contratual. Essa premissa é extremamente importante para a hipótese de indenização securitária decorrente de suicídio, pois dela extraise que a presunção de boa fé deverá também prevalecer sobre a exegese literal do art. 798 do Código Civil 2002. O período de 02 anos contido na norma não deve ser examinado isoladamente, mas em conformidade com as demais circunstâncias que envolveram sua elaboração, pois seu objetivo certamente não foi substituir a prova da premeditação do suicídio pelo mero transcurso de um lapso temporal. Há de se distinguir a premeditação que diz respeito ao ato do suicídio daquela que se refere ao ato de contratar o seguro com afinalidade única de favorecer o beneficiário que receberá o capital segurado. Somente a última hipótese permite a exclusão da cobertura contratada, pois configura a má-fé contratual. Em Portugal, salvo em raras exceções, apenas o critério temporal tem sido considerado. Continuando com o objetivo deste estudo, pretendeu-se refletir sobre as pesquisas neurocientíficas acerca do suicídio e, nelas, constam aspectos efetivamente que merecem ser considerados pela ciência jurídica. Suicídio é tema complexo e digno de reflexões por parte de profissionais de várias áreas de atuação. Suas causas ainda são motivo de curiosidade e de investigação. A idéia de uma associação entre disfunção serotoninérgica e suicídio é antiga e bastante consistente, surgindo ainda nos anos 1970 com as primeiras pesquisas. Defende-se que a boa fé necessária nos contratos de seguro, especialmente nos de seguro de vida, prevalece mesmo nos casos em que o contratante se esquece ou deixa de informar algum detalhe que, mais tarde, possa vir a comprometer o recebimento do prêmio por seus beneficiários. Há fortes evidências de que determinantes neurobiológicos, independentes das doenças psiquiátricas, implicam em comportamento suicida, estudados especialmente nos últimos 20 anos. Assim, noções básicas sobre a neurobiologia do suicídio podem finalmente produzir ferramentas clínicas para tratar comportamento suicida e evitar mortes, além de poder nortear seguradoras na análise de propostas de seguros de vida. Textos legais não têm sido elaborados com fundamento na sedimentação existente nos repositórios da psicopatologia forense, psiquiatria, psicanálise e sociologia sobre o suicídio, disponíveis há décadas e de forma reiteradamente confirmados. Na mesma linha, os textos deixaram de lado incontáveis pesquisas sobre o tema, notadamente a respeito de sua etiologia, causas primárias, efeitos, e correlação com outras ciências, como neurociência, psiquiatria e psicanálise. Não buscaram informações sobre o comportamento singular do suicida, nem reconheceram o estado sui generis de desequilíbrio mental em que o ato final foi praticado. Sabe-se que os transtornos psiquiátricos são fundamentais para o entendimento do comportamento suicida, mas também já está comprovada a realidade de problemas comuns, como distúrbios do sono, e sono insuficiente é um problema da sociedade moderna. Dentre os neurotransmissores, a serotonina é considerada como a maior candidata a um vínculo etiológico entre distúrbios do sono e suicídio, pois suas alterações promovem estados de vigília e de início do sono. Como somente 14% de pessoas que tentaram suicídio tiveram pensamentos suicidaprévios à tentativa de suicídio de forma potencialmente impulsiva ou reativa, a insônia foi o fator importante visualizado antes de tentativas de suicídio graves e letais em relação a planosespecíficos de suicídio. Nas pesquisas neurocientíficas revisadas, constatou-se que: (1) a frequência de pesadelos está diretamente associada a maior risco de suicídios na população em geral; (2) sono de má qualidade está associado a suicídios na maturidade e velhice na população em geral; (3) sono curto (menos de cinco horas) está associado a maiores probabilidades de ideação suicida e tentativa de suicídio; (4) pesadelos frequentes são preditores de tentativas de suicídio; e (5) a presença de qualquer problema de sono está associada com maior risco de suicídio na população em geral. A associação entre redução da resposta de hormônio de crescimento e comportamento suicida nos pacientes com depressão só é encontrada quando há simultaneamente uma alteração serotoninérgica. Geneticamente analisados, determinantes neurobiológicos são independentes de transtorno psiquiátrico com o qual estão associados, pois muitos suicídios ocorrem de maneira inesperada. Além disso, quando se considera a depressão como único fator, percebe-se que muitas pessoas depressivas nunca se tornam suicidas e muitos suicídios são cometidos por pessoas consideradas normais.Quanto à colesterolemia, na maior categoria de concentração de colesterol total no soro, o risco relativo ajustado de suicídio violento é mais do que o dobro em comparação com a categoria mais baixa. Nas avaliações eletroencefalográficas em adolescentes suicidas pode-se dizer existir uma hipótese de ativação reduzida esquerda posterior, que não está relacionada à depressão, mas ao comportamento agressivo ou suicida. Essas abordagens da Neurociência servem, portanto, para indicar que um contratante de seguro de vida, mesmo saudável, pode estar vivenciando problemas da vida contemporânea e, mesmo sem jamais ter tido qualquer pensamento ou ideação suicida, vir a cometer esse ato extremo por alterações independentes de sua vontade. Entende-se que, neste foco, a ciência jurídica deve refletir para fazer inserir de maneira obrigatória nos pré-requisitos da apólice, informações sobre exames molecu-lares e sobre algum eventual distúrbio do sono, já que existem achados evidenciados sobre alguns fenômenos não antes considerados. Como abordado neste estudo, já existe uma seguradora portuguesa que solicitam exames moleculares, mas nenhuma no Brasil. Assim, isto indica já ser um início de mudança.

Biased technological change, human capital and factor shares

We propose a one-good model where technological change is factor saving and costly. We consider a production function with two reproducible factors: physical capital and human capital, and one not reproducible factor. The main predictions of the model are the following: (a) The elasticity of output with respect to the reproducible factors depends on the factor abundance of the economies. (b) The income share of reproducible factors increases with the stage of development. (c) Depending on the initial conditions, in some economies the production function converges to AK, while in other economies long-run growth is zero. (d) The share of human factors (raw labor and human capital) converges to a positive number lower than one. Along the transition it may decrease, increase or remain constant.

Endocrine regulation of ovarian antral follicle development in cattle

Antral follicle growth in cattle occurs in two distinct phases; the first 'slow' growth phase spans the time from antrum acquisition to a size of approximately 3 mm detectable by transrectal ultrasound, and the second 'fast' phase is gondadotrophin-dependent and includes cohort growth, dominant follicle (DF) selection, and DF growth. This review summarises current concepts of the relative roles FSH and LH, ovarian and metabolic hormones play mainly in the second phase of antral follicle growth in animals of different reproductive and nutritional states. It is proposed that differential FSH response may enable one cohort follicle to become selected, and that follicular secretions, particularly inhibin, suppress FSH and thus are responsible for DF selection and dominance. Acute dependence of the DF on LH pulses will determine DF lifespan, and the LH pulse profile can be influenced by metabolic hormones such as leptin, providing one possible link for nutritional state and reproduction. Direct ovarian effects of acute and chronic changes in growth hormone, insulin and insulin-like growth factor (IGF)-I have been described on cohort follicles, DF oestrogen activity and on DF growth. Influences of metabolic hormones on early antral follicles undergoing their first 'slow' growth phase are less well described, yet metabolic hormones appear to enhance growth into the cohort available for FSH-induced emergence, and may influence subsequent developmental competence of oocytes. (C) 2003 Elsevier Science B.V. All rights reserved.

First lactation ovarian function in dairy heifers in relation to prepubertal metabolic profiles

The aim of this study was to determine whether any differences in the GH-IGF-I axis in juvenile calves were predictive of fertility problems as adult cows. Endogenous metabolic hormone profiles before and after feeding and the response to a GH-releasing factor (GRF) challenge were measured in prepubertal (6 month) dairy calves. These metabolic parameters were subsequently related to physical characteristics at puberty and to ovarian function during the first lactation. Milk progesterone analysis was used to categorize the animals into those with normal progesterone profiles following calving (n = 17) and those that developed delayed ovulation (DOV1, n = 9) or persistent corpus luteum (PCL1, n = 6) profiles. There were associations between prepubertal GH parameters, glucose and non-esterified fatty acid (NEFA) concentrations and the body condition score at which the animals attained puberty. The calves which subsequently developed DOV1 profiles as cows tended to have a higher GH pulse amplitude during fasting than normal profile animals, they did not show the anticipated decrease in circulating glucose concentrations following a post-prandial rise in insulin and they also had the lowest IGF-I concentrations. The calves that later developed PCL1 had a significantly larger GH pulse amplitude and pulse area than normal profile animals in the fed period and had the highest IGF-I concentrations. There were no differences in prepubertal insulin or NEFA concentrations or in the GH response to a GRF challenge between the different progesterone profile categories. Plasma IGF-I concentrations in prepubertal animals were positively correlated with their post-calving concentrations, whereas glucose concentrations had a negative correlation between these time-periods. These results suggested that the different juvenile endocrine profiles of the DOV1 cows may predispose them to a higher rate of tissue mobilization during lactation and a consequent reduction in fertility, while altered GH and IGF-I levels in PCL1 cows may later contribute to the maintenance of the persistent corpus luteum. Therefore metabolic differences in prepubertal calves were later reflected by altered reproductive function during the first lactation.

TGF-beta superfamily members and ovarian follicle development

In recent years, exciting progress has been made towards unravelling the complex intraovarian control mechanisms that, in concert with systemic signals, coordinate the recruitment, selection and growth of follicles from the primordial stage through to ovulation and corpus luteum formation. A plethora of growth factors, many belonging to the transforming growth factor-beta (TGF-beta) superfamily, are expressed by ovarian somatic cells and oocytes in a developmental, stage-related manner and function as intraovarian regulators of folliculogenesis. Two such factors, bone morphogenetic proteins, RMP-4 and BMP-7, are expressed by ovarian stromal cells and/or theca cells and have recently been implicated as positive regulators of the primordial-to-primary follicle transition. In contrast, evidence indicates a negative role for anti-Mullerian hormone (AMH, also known as Mullerian-inhibiting substance) of pre-granulosa/granulosa cell origin in this key event and subsequent progression to the antral stage. Two other TGF-beta superfamily members, growth and differentiation factor-9 (GDF-9) and BMP-15 (also known as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play key roles in promoting follicle growth beyond the primary stage; mice with null mutations in the gdf-9 gene or ewes with inactivating mutations in gdf-9 or bmp-15 genes are infertile with follicle development arrested at the primary stage. Studies on later stages of follicle development indicate positive roles for granulosa cell-derived activin, BMP-2, -5 and -6, theca cell-derived BMP-2, -4 and -7 and oocyte-derived BMP-6 in promoting granulosa cell proliferation, follicle survival and prevention of premature luteinization and/or atresia. Concomitantly, activin, TGF-beta and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection in monovular species may depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Changes in intrafollicular activins, GDF-9, AMH and several BMPs may contribute to this selection process by modulating both FSH- and IGF-dependent signalling pathways in granulosa cells. Activin may also play a positive role in oocyte maturation and acquisition of developmental competence. in addition to its endocrine role to suppress FSH secretion, increased output of inhibin by the selected dominant follicle(s) may upregulate LH-induced androgen secretion that is required to sustain a high level of oestradiol secretion during the pre-ovulatory phase. Advances in our understanding of intraovarian regulatory mechanisms should facilitate the development of new approaches for monitoring and manipulating ovarian function and improving fertility in domesticated livestock, endangered species and man.

The ACTH response to dexamethasone in PTSD

Objective: Enhanced negative feedback and reduced adrenal output are two different models that have been put forth to explain the paradoxical observations of increased release of corticotropin-releasing factor in the face of low cortisol levels in posttraumatic stress disorder (PTSID). To discriminate between these models, the authors measured levels of adrenocorticopic hormone (ACTH) and cortisol at baseline and in response to dexamethasone in medically healthy subjects with and without PTSID. Under conditions of enhanced negative feedback inhibition, ACTH levels would not be altered relative to cortisol levels, but the ACTH response to dexamethasone would be augmented, in concert with the enhanced cortisol response to dexamethasone. In contrast, under conditions of reduced adrenal output, ACTH levels would be expected to be higher at baseline relative to cortisol levels, but the ACTH response to dexamethasone would be unchanged in PTSID relative to healthy comparison subjects. Method: The ACTH and cortisol responses to 0.50 mg of dexamethasone were assessed in 19 subjects (15 men and four women) with PTSID and 19 subjects (14 men and five women) without psychiatric disorder. Results: The ACTH-to-cortisol ratio did not differ between groups before or after dexamethasone, but the subjects with PTSD showed greater suppression of ACTH (as well as cortisol) in response to dexamethasone. Conclusions: The data support the hypothesis of enhanced cortisol negative feedback inhibition of ACTH secretion at the level of the pituitary in PTSD. Pituitary glucocorticoid receptor binding, rather than low adrenal output, is implicated as a likely mechanism for this effect.

Chronic supplementation of beta-hydroxy-beta methylbutyrate (HM beta) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats

Objective: Beta-hydroxy-beta-methylbutyrate (HM beta) is a metabolite of leucine widely used for improving sports performance. Although limp is recognized to promote anabolic or anti-catabolic effects on protein metabolism, the impact of its long-term use on skeletal muscle and/or genes that control the skeletal protein balance is not fully known. This study aimed to investigate whether chronic HM beta treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and myostatin mRNA expression. Design: Rats were treated with HK beta (320 mg/kg BW) or vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected for total RNA or protein extraction to evaluate the expression of pituitary growth hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I) mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR, or Western blotting. Results: Chronic HM beta treatment increased the content of pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No changes were detected on skeletal muscle IGF-I and myostatin mRNA expression. However, the HIM-treated rats although normoglycemic, exhibited hyperinsulinemia. Conclusions: The data presented herein extend the body of evidence on the potential role of HM beta-treatment in stimulating GH/IGF-I axis activity. In spite of this effect, HM beta supplementation also induces an apparent insulin resistance state which might limit the beneficial aspects of the former results, at least in rats under normal nutritional status and health conditions. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

T3 acutely increases GH mRNA translation rate and GH secretion in hypothyroid rats

Cytoskeleton controls the stability of transcripts, by mechanisms that involve mRNAs and eEF1A attachment to it. Besides, it plays a key role in protein synthesis and secretion, which seems to be impaired in somatotrophs of hypothyroid rats, whose cytoskeleton is disarranged. This study investigated the: eEF1A and GH mRNA binding to cytoskeleton plus GH mRNA translation rate and GH secretion, in sham-operated and thyroidectomized rats treated with T3 or saline, and killed 30 min thereafter. Thyroidectomy reduced: (a) pituitary F-actin content, and eEF1A plus GH mRNA binding to it; (b) GH mRNA recruitment to polysome; and (c) liver IGF-1 mRNA expression, indicating that GH mRNA stability and translation rate, as well as GH secretion were impaired. T3 acutely reversed all these changes, which points toward a nongenomic action of T3 on cytoskeleton rearrangement, which might contribute to the increase on GH mRNA translation rate and GH secretion. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Reduced maximal oxygen consumption and overproduction of proinflammatory cytokines in athletes

Objective: It was the aim of this study to evaluate whether chronic pain in athletes is related to performance, measured by the maximum oxygen consumption and production of hormones and cytokines. Methods: Fifty-five athletes with a mean age of 31.9 +/- 4.2 years engaged in regular competition and showing no symptoms of acute inflammation, particularly fever, were studied. They were divided into 2 subgroups according to the occurrence of pain. Plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, growth hormone and dopamine were measured by radioimmunoassay, and the production of the cytokines interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor-alpha, interferon-alpha and prostaglandin E-2 by whole-blood culture. Maximal oxygen consumption was determined during an incremental treadmill test. Results: There was no change in the concentration of stress hormones, but the athletes with chronic pain showed a reduction in maximum oxygen consumption (22%) and total consumption at the anaerobic threshold (25%), as well as increased cytokine production. Increases of 2.7-, 8.1-, 1.7- and 3.7-fold were observed for IL-1, IL-2, tumor necrosis factor-alpha and interferon-alpha, respectively. Conclusions: Our data show that athletes with chronic pain have enhanced production of proinflammatory cytokines and lipid mediators and reduced performance in the ergospirometric test. Copyright (c) 2008 S. Karger AG, Basel.

Redistribution of glucose from skeletal muscle to adipose tissue during catch-up fat. A link between catch-up growth and later metabolic syndrome.

Catch-up growth, a risk factor for later obesity, type 2 diabetes, and cardiovascular diseases, is characterized by hyperinsulinemia and an accelerated rate for recovering fat mass, i.e., catch-up fat. To identify potential mechanisms in the link between hyperinsulinemia and catch-up fat during catch-up growth, we studied the in vivo action of insulin on glucose utilization in skeletal muscle and adipose tissue in a previously described rat model of weight recovery exhibiting catch-up fat caused by suppressed thermogenesis per se. To do this, we used euglycemic-hyperinsulinemic clamps associated with the labeled 2-deoxy-glucose technique. After 1 week of isocaloric refeeding, when body fat, circulating free fatty acids, or intramyocellular lipids in refed animals had not yet exceeded those of controls, insulin-stimulated glucose utilization in refed animals was lower in skeletal muscles (by 20–43%) but higher in white adipose tissues (by two- to threefold). Furthermore, fatty acid synthase activity was higher in adipose tissues from refed animals than from fed controls. These results suggest that suppressed thermogenesis for the purpose of sparing glucose for catch-up fat, via the coordinated induction of skeletal muscle insulin resistance and adipose tissue insulin hyperresponsiveness, might be a central event in the link between catch-up growth, hyperinsulinemia and risks for later metabolic syndrome.

Blood plasma concentrations of metabolic hormones and glucose during extended lactation in grazing cows or cows fed a total mixed ration

An experiment was conducted to measure the effect of diet on circulating concentrations of metabolic hormones and metabolites in cows undergoing extended lactations. Two groups of 6 Holstein-Friesian cows managed for lactations of 670 d were used in the experiment. One group was fully fed on a total mixed ration (TMR), whereas the other group grazed fresh pasture supplemented with grain (P+G). On 7 occasions between 332 and 612 d in milk, concentrations of metabolic hormones and glucose were measured in the blood plasma of each cow. Cows fed TMR gained more weight and body condition than P+G cows, but did not produce more milk during the study period. Only 3 of the TMR cows continued to lactate until 612 d in milk compared with all 6 of the P+G cows. Blood plasma from cows fed TMR had higher concentrations of glucose, insulin, glucagon, insulin-like growth factor 1, and leptin, but lower concentrations of growth hormone, than that from P+G cows. These changes were consistent with the preferential deposition of energy into adipose tissue at the expense of milk production and presumably were induced by a diet that provided precursors for gluconeogenesis that were in excess of the requirements for maintenance and prevailing milk production. The mechanism responsible for some TMR cows putting on excess weight and reducing or ceasing milk production is uncertain, but this observation has important implications for the nutritional management of cows in extended lactation programs.

Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin-1β

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic–pituitary–adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic–pituitary–adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1β. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic–pituitary–adrenal axis responses to systemic interleukin-1β, we next mapped the effects of similar lesions on interleukin-1β-induced Fos expression in regions previously shown to regulate the hypothalamic–pituitary–adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1β, an outcome that is difficult to reconcile with a simple medial prefrontal cortex–bed nucleus of the stria terminalis–corticotropin-releasing factor cell control circuit.