A proliferação das células do córtex adrenal é um fenômeno que envolve genes e proteínas relacionados com o controle do ciclo celular. Um dos principais fatores envolvidos na proliferação do córtex adrenal é o ACTH (hormônio corticotrófico), mas outros fatores, como o peptídeo N-terminal da POMC, parece estar envolvido. Para contribuir com o entendimento dos mecanismos envolvidos na resposta proliferativa do córtex adrenal analisamos os efeitos desencadeados por ambos os peptídeos em ratos cujo eixo HPA foi inibido pela dexametasona. Foram utilizados os métodos de incorporação de BrdU; de análise da expressão proteica das ciclinas D, E e p27 através de imunistoquímica e immunoblotting e da expressão de genes relacionados ao controle do ciclo celular utilizando placas de qRT-PCR. Nossos resultados sugerem que ambos os peptídeos induzem efeito proliferativo mas zona-específico no córtex adrenal, e que esse efeito pode ser mediado pelo controle da expressão das ciclinas D2, D3 e E, e pelo inibidor de ciclo celular, a proteína p27kip1. / The proliferation of adrenal cortical cells involves genes and proteins related with the control of the cell cycle. The main factor involved in the proliferation of the adrenal cortex is the ACTH (corticotrophin), but other factor, such as the peptide N-terminal of POMC, seems to be involved. To contribute to the understanding of the mechanisms involved in the proliferative response of the adrenal cortex, we analyzed the effects triggered by both peptides in rats with the HPA axis inhibited by dexamethasone. The methods used were the incorporation of BrdU; analysis of protein cyclins D, E and p27 expression through immunohistochemistry and immunoblotting and expression of genes involved in cell cycle regulation by using qRT-PCR arrays. The results suggest that both peptides induced proliferative effect in adrenal cortex in a zone-specific manner. This effect may be mediated by the control of cyclins D2, D3 and E expression, and also by the cell cycle inhibitor, protein p27KIP1.

Um dos fatores que regula o córtex adrenal é o hormônio adrenocorticotrópico, ACTH, no entanto, o fator de crescimento de fibroblastos do tipo 2, FGF2, e os peptídeos N-terminais da pro-opiomelanocortina, N-POMC, também podem estar envolvidos. As vias de sinalização das proteínas quinases: ERK, JNK e p38, juntamente com outras vias como PKA, PKC e PI3K/Akt são importantes para a definição trófica das células. Nós analisamos a importância destas vias de sinalização e sua influência na viabilidade, proliferação e morte celular, induzidas pelo ACTH, FGF2 e N-POMC, utilizando inibidores farmacológicos e moleculares em culturas primárias de células adrenocorticais, células glomerulosa e fasciculadas/reticulares. Nossos resultados mostram que as vias mediadoras envolvidas na resposta proliferativa do FGF2 e da N-POMC são, respectivamente, as vias ERK/JNK e ERK/JNK/Akt. Por outro lado, a resposta pró-apoptótica promovida pelo ACTH é mediada pela via p38, provavelmente associada à ausência de ativação das vias relacionadas com a sobrevivência, como as vias ERK e JNK. / One of the factors that regulate adrenal cortex is the adrenocorticotrophic hormone, ACTH, however, the fibroblast growth factor type 2, FGF2) and pro-opiomelanocortin N-terminal peptides, N-POMC, might also be involved. The mitogen-activated protein kinase pathways: ERK, JNK and p38, together with other signaling pathways such as PKA, PKC and PI3K/Akt are important for cells trophic definition. We analyze the importance of these pathways and their influence in viability, proliferation and cell death stimulated by ACTH, FGF2 and N-POMC, using pharmacological and molecular inhibitors in primary culture of adrenocortical cells, glomerulosa and fasciculata/reticularis cells. Our results show that the mediating signaling pathways involved in FGF2 and N-POMC proliferative effects are, respectively, ERK/JNK and ERK/JNK/Akt. On the other hand, the pro-apoptotic response promoted by ACTH is through p38 signaling, probably associated with the absence of activation of other pathways involved with cell survival, like ERK and JNK.

Pup directed maternal licking and grooming (LG) increases with corticosterone (CORT) supplimentation (Rees et al 2004). Increases in LG lead to an attenuation of the adult offspring's HPA response to stress (Liu et aI1997). Similarly, Neonatal increases in glucocorticoids lead, in adulthood, to the same attenuation of the HPA stress response (Catalani et aI1993). We hypothesize that dams exhibiting increased LG will have increased circulating CORT, and this increase will be reflected in their offspring. This thesis characterizes the HPA hormone profile adrenocorticotropic hormone (ACTH), CORT & Corticosterone Binding Globulin (CBG) in High LG (H) and Low LG (L) litters, 5 days postpartum (P4). Furthermore pup plasma CORT levels are determined at (P) 3,4,6,10 & 14. Finally P10 Hand L LG ACTH, CORT & CBG will be assessed after stress. RESULTS: H compared to L LG dams have significantly increased plasma CORT (p=0.03). At P4, H LG offspring have significantly increased plasma CORT (p=0.03) and significantly decreased plasma ACTH (p=0.04) as compared to L LG offspring. Plasma CBG levels are significantly lower in H compared to L LG offspring (p=0.01) at the same age. Across the Stress Hyporesponsive Period (SHRP) H LG offspring had significantly increased plasma CORT (p= 0.00) compared to L LG offspring at P3. Challenged with a stressor at P10, H LG offspring have an exaggerated plasma CORT response (p=0.00). This data suggests increases in plasma CORT in the dams leads to increased CORT in the high offspring, contributing perhaps to a more mature stress response at P10. / Key word abbreviation: (1) CORT - CORTicosterone, (2) ACTH - AdrenoCorticoTropin releasing Hormone, (3) CBG - Corticosteroid Binding Globulin, (4) SHRP - Stress Hypo-Responsive Period, (5) P - Post-natal day, (6) HPA - Hypothalamic-Pituitary-Adrenal, (7) LG - Licking/Grooming, (8) ADX/OVX - ADrenalectomized/OVarectomized.

We present the case of a 7-month-old baby with Cushing’s disease due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma combined with cells producing thyreotropin-secreting hormone (TSH). In MRI scans, a contrast-enhancing lesion was seen inside the pituitary fossa, and it extended into the suprasellar region. On the assumption of a pituitary adenoma, surgery was performed. Corresponding with biochemical findings, histopathological evaluation revealed an ACTH- and TSH-producing tumor. Genetic analysis did not demonstrate an alteration at codon 201 (Arg) and 227 (Glu). To our knowledge, this is the first case described in a child of this age. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Adrenal insufficiency is common in pediatric patients with septic shock, but remains underdiagnosed in the early stages of sepsis. The early recognition of the factors representing risk for septic shock is crucial, since no control of them can increase the risk of death. This study aimed to verify the occurrence of adrenal insufficiency and describe the clinical and initial laboratory findings in children hospitalized for sepsis. This was a descriptive study, which included children admitted to the Pediatric Intensive Care Unit of the University Hospital of Santa Maria, in the period from March to October, 2013. We studied five patients with sepsis. For adrenal insufficiency diagnoses we performed the ACTH stimulation test. A positive test was considered when an increment on the cortisol level equal or less 9 μg/dL occurred. Five children were analyzed, 80 % were male with a mean age of 7.3 years (±4.2). The initial laboratorial findings confirmed the presence of sepsis. Adrenal insufficiency was diagnosed in 2 of 5 patients studied, representing 40 %. Only one patient (20%) required mechanical ventilation. There was no progression to septic shock in any of the patients studied. All patients were discharges from hospital. We concluded that adrenal insufficiency may be present in pediatric patients with sepsis, in its earliest stages. / A insuficiência adrenal é comum em pacientes pediátricos com choque séptico, porém permanece subdiagnosticada nas fases mais precoces da sepse. Reconhecer precocemente os fatores de progressão para o choque séptico é de fundamental importância, uma vez que, o não controle dos mesmos favorece a lesão de órgãos nobres, aumentando, dessa forma, o risco de morte. Este estudo teve por objetivo verificar a ocorrência de insuficiência adrenal e descrever a evolução clínica e os achados laboratoriais iniciais em crianças internadas por sepse. Estudo descritivo, tipo série de casos, que incluiu crianças admitidas na Unidade de Terapia Intensiva Pediátrica do Hospital Universitário de Santa Maria, no período de março/2013 a outubro/2013. Foram estudados pacientes com diagnóstico de sepse. A insuficiência adrenal foi diagnosticada através da realização do teste de estimulação com ACTH (teste da cortrosina). O nível de cortisol foi dosado imediatamente antes (basal) e uma hora após a administração venosa de 250 μg do análogo sintético do ACTH. Um incremento menor ou igual a 9 μ/dL no cortisol sérico definiu insuficiência adrenal. Foram estudadas 5 crianças, sendo 80% do sexo masculino, com idade média de 7,3 anos (±4,2). Os achados laboratoriais iniciais confirmavam presença de sepse. Insuficiência adrenal foi diagnosticada em 2 dos 5 pacientes, representando 40%. Apenas um paciente (20%) necessitou de suporte ventilatório. Não houve evolução para choque séptico em nenhum dos pacientes estudados. Todos os pacientes receberam alta hospitalar. Concluiu-se a insuficiência adrenal pode estar presente, em pacientes pediátricos com diagnóstico de sepse, nas suas fases mais precoces.

Made available in DSpace on 2015-07-22T20:49:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Em pacientes com diabetes mellitus tipo 1 (DM1) foram observadas respostas normais ou aumentadas de GH apos estimulos. O eixo hipotalamo- hipofiseadrenal tem sido menos estudado. A ghrelina e um secretagogo de GH que tambem aumenta os niveis de ACTH e de cortisol, de forma semelhante ao GHRP-6. Nao existem estudos sobre os efeitos da ghrelina em pacientes com DM1. O objetivo do presente trabalho foi avaliar as respostas do GH, ACTH e cortisol a ghrelina e ao GHRP-6 em 9 pacientes com DM1 (HbA1c: 11.7 } 1,3%; media } SE) e em 9 individuos normais. A liberacao de GH induzida por GHRH tambem foi estudada. A media dos niveis basais de GH (ƒÊg/L) foi maior nos pacientes com DM1 (3.5 } 1.2) do que nos controles (0.6 } 0.3). Analisando AASC GH (ƒÊg/L.120min), nao foram observadas diferencas significantes entre os diabeticos (ghrelina: 3.148 } 427; GHRP-6: 1428 } 299; GHRH: 885 } 184) e os controles (ghrelina: 3228 } 1036 ; GHRP-6: 1271 } 217; GHRH: 643 } 178). Em ambos os grupos, a liberacao de GH induzida pela ghrelina foi maior do que apos GHRP-6 e GHRH. Houve uma tendencia (p = 0.055) a elevacao dos niveis de cortisol basal (ƒÊg/dL) nos pacientes com DM1 (11.7 } 1.5) comparado aos controles (8.2 } 0.8). Nao foram observadas diferencas significantes nos valores de AASC cortisol (ƒÊg/dL.90min) entre os grupos apos ghrelina (DM1: 303 } 106; controles: 467 } 86) e GHRP-6 (DM1: 135 } 112; controles: 187 } 73). A media de valores basais de ACTH (pg/mL) foi semelhante nos diabeticos (19.9 } 3.4) e nos controles (14.5 } 2.3). Nao foram observadas diferencas nos valores de AASC ACTH (pg/mL.90min) entre os grupos apos ghrelina (DM1: 1372 } 771; controles: 1394 } 327) e GHRP-6 (DM1: 257 } 291; controles: 423 } 211). Em resumo, os pacientes com DM1 tem resposta normal do GH a ghrelina, GHRP-6 e GHRH. A liberacao de ACTH e cortisol apos ghrelina e GHRP-6 tambem e semelhante aos controles. Nossos resultados sugerem que a hiperglicemia cronica do DM1 nao interfere com a liberacao de GH, ACTH e cortisol estimulada por estes peptideos. / In type 1 diabetes mellitus (T1DM), GH responses to provocative stimuli are normal or exaggerated while the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH-secretagogue which also increases ACTH and cortisol levels, similarly to GHRP-6. Ghrelin Ls effects in patients with T1DM have not been evaluated. We, therefore, studied GH, ACTH and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1D1 (HbA1c: 11.7 }1.3%; mean }SE) and 9 control subjects. GHRH- induced GH release was also evaluated. Mean basal GH levels (Rg/L) were higher in T1DM (3.5 }1.2) than in controls (0.6 }0.3). Analyzing ƒ¢AUC GH values (Rg/L.120min), no significant differences were observed in T1DM (ghrelin: 3148 }427; GHRP-6: 1428 }299; GHRH: 885 }184) compared to controls (ghrelin: 3228 }1036; GHRP-6: 1271 }217; GHRH: 643 }178). In both groups, ghrelin-induced GH release was higher than after GHRP-6 and GHRH. There was a trend (p=0.055) to higher mean basal cortisol values (Rg/dL) in T1DM (11.7 }1.5) compared to controls (8.2 }0.8). No significant differences were seen in ƒ¢AUC cortisol values (Rg/dL.90min) in both groups after ghrelin (DM1:303 }106; controls: 467 }86) and GHRP-6 (DM1:135 }112; controls: 187 }73). Mean basal ACTH values (pg/mL) were similar in T1DM (19.9 }3.4) and controls (14.5 }2.3). No differences were seen in ƒ¢AUC ACTH levels (pg/mL.90min) in both groups after ghrelin (DM1:1372 }771; controls: 1394 }327) and GHRP-6 (DM1: 257 }291; controls: 423 }211). In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6 and GHRH. ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH, ACTH and cortisol releasing mechanisms stimulated by these peptides. / TEDE / BV UNIFESP: Teses e dissertações

Um dos fatores que regula o córtex adrenal é o hormônio adrenocorticotrópico, ACTH, no entanto, o fator de crescimento de fibroblastos do tipo 2, FGF2, e os peptídeos N-terminais da pro-opiomelanocortina, N-POMC, também podem estar envolvidos. As vias de sinalização das proteínas quinases: ERK, JNK e p38, juntamente com outras vias como PKA, PKC e PI3K/Akt são importantes para a definição trófica das células. Nós analisamos a importância destas vias de sinalização e sua influência na viabilidade, proliferação e morte celular, induzidas pelo ACTH, FGF2 e N-POMC, utilizando inibidores farmacológicos e moleculares em culturas primárias de células adrenocorticais, células glomerulosa e fasciculadas/reticulares. Nossos resultados mostram que as vias mediadoras envolvidas na resposta proliferativa do FGF2 e da N-POMC são, respectivamente, as vias ERK/JNK e ERK/JNK/Akt. Por outro lado, a resposta pró-apoptótica promovida pelo ACTH é mediada pela via p38, provavelmente associada à ausência de ativação das vias relacionadas com a sobrevivência, como as vias ERK e JNK. / One of the factors that regulate adrenal cortex is the adrenocorticotrophic hormone, ACTH, however, the fibroblast growth factor type 2, FGF2) and pro-opiomelanocortin N-terminal peptides, N-POMC, might also be involved. The mitogen-activated protein kinase pathways: ERK, JNK and p38, together with other signaling pathways such as PKA, PKC and PI3K/Akt are important for cells trophic definition. We analyze the importance of these pathways and their influence in viability, proliferation and cell death stimulated by ACTH, FGF2 and N-POMC, using pharmacological and molecular inhibitors in primary culture of adrenocortical cells, glomerulosa and fasciculata/reticularis cells. Our results show that the mediating signaling pathways involved in FGF2 and N-POMC proliferative effects are, respectively, ERK/JNK and ERK/JNK/Akt. On the other hand, the pro-apoptotic response promoted by ACTH is through p38 signaling, probably associated with the absence of activation of other pathways involved with cell survival, like ERK and JNK.

A proliferação das células do córtex adrenal é um fenômeno que envolve genes e proteínas relacionados com o controle do ciclo celular. Um dos principais fatores envolvidos na proliferação do córtex adrenal é o ACTH (hormônio corticotrófico), mas outros fatores, como o peptídeo N-terminal da POMC, parece estar envolvido. Para contribuir com o entendimento dos mecanismos envolvidos na resposta proliferativa do córtex adrenal analisamos os efeitos desencadeados por ambos os peptídeos em ratos cujo eixo HPA foi inibido pela dexametasona. Foram utilizados os métodos de incorporação de BrdU; de análise da expressão proteica das ciclinas D, E e p27 através de imunistoquímica e immunoblotting e da expressão de genes relacionados ao controle do ciclo celular utilizando placas de qRT-PCR. Nossos resultados sugerem que ambos os peptídeos induzem efeito proliferativo mas zona-específico no córtex adrenal, e que esse efeito pode ser mediado pelo controle da expressão das ciclinas D2, D3 e E, e pelo inibidor de ciclo celular, a proteína p27kip1. / The proliferation of adrenal cortical cells involves genes and proteins related with the control of the cell cycle. The main factor involved in the proliferation of the adrenal cortex is the ACTH (corticotrophin), but other factor, such as the peptide N-terminal of POMC, seems to be involved. To contribute to the understanding of the mechanisms involved in the proliferative response of the adrenal cortex, we analyzed the effects triggered by both peptides in rats with the HPA axis inhibited by dexamethasone. The methods used were the incorporation of BrdU; analysis of protein cyclins D, E and p27 expression through immunohistochemistry and immunoblotting and expression of genes involved in cell cycle regulation by using qRT-PCR arrays. The results suggest that both peptides induced proliferative effect in adrenal cortex in a zone-specific manner. This effect may be mediated by the control of cyclins D2, D3 and E expression, and also by the cell cycle inhibitor, protein p27KIP1.

Communication signals are shaped by the opposing selection pressures imposed by predators and mates. A dynamic signal might serve as an adaptive compromise between an inconspicuous signal that evades predators and an extravagant signal preferred by females. Such a signal has been described in the gymnotiform electric fish, Brachyhypopomus gauderio, which produces a sexually dimorphic electric organ discharge (EOD). The EOD varies on a circadian rhythm and in response to social cues. This signal plasticity is mediated by the slow action of androgens and rapid action of melanocortins. My dissertation research tested the hypotheses that (1) signal plasticity is related to sociality levels in gymnotiform species, and (2) differences in signal plasticity are regulated by differential sensitivity to androgen and melanocortin hormones. To assess the breadth of dynamic signaling within the order Gymnotiformes, I sampled 13 species from the five gymnotiform families. I recorded EODs to observe spontaneous signal oscillations after which I injected melanocortin hormones, saline control, or presented the fish with a conspecific. I showed that through the co-option of the ancient melanocortin pathway, gymnotiforms dynamically regulate EOD amplitude, spectral frequency, both, or neither. To investigate whether observed EOD plasticities are related to species-specific sociality I tested four species; two territorial, highly aggressive species, Gymnotus carapo and Apteronotus leptorhynchus, a highly gregarious species, Eigenmannia cf. virescens, and an intermediate short-lived species with a fluid social system, Brachyhypopomus gauderio. I examined the relationship between the androgens testosterone and 11-ketotestosterone, the melanocortin a-MSH, and their roles in regulating EOD waveform. I implanted all fish with androgen and blank silicone implants, and injected with a-MSH before and at the peak of implant effect. I found that waveforms of the most territorial and aggressive species were insensitive to hormone treatments; maintaining a static, stereotyped signal that preserves encoding of individual identity. Species with a fluid social system were most responsive to hormone treatments, exhibiting signals that reflect immediate condition and reproductive state. In conclusion, variation in gymnotiform signal plasticity is hormonally regulated and seems to reflect species-specific sociality.

No description available.