Hemodynamic and hormonal actions of adrenomedullin

Adrenomedullin, a 52-amino acid residue peptide, has numerous biological actions which are of potential importance to cardiovascular homeostasis, growth and development of cardiovascular tissues and bone, prevention of infection, and regulation of body fluid and electrolyte balance. Studies in man using intravenous infusion of the peptide have demonstrated that, at plasma levels detected after myocardial infarction or in heart failure, adrenomedullin reduces arterial pressure, increases heart rate and cardiac output, and activates the sympathetic and renin-angiotensin systems but suppresses aldosterone. The thresholds for these responses differ, being lower under some experimental circumstances for arterial pressure than for the other biological effects. Adrenomedullin administration inhibits the pressor and aldosterone-stimulating action of angiotensin II in man. By contrast, the pressor effect of norepinephrine is little altered by concomitant adrenomedullin administration. Although in the absence of a safe, specific antagonist of the actions of endogenous adrenomedullin it is difficult to be certain about the physiological and pathophysiological importance of this peptide in man, current evidence suggests that it serves to protect against cardiovascular overload and injury. Hope has been expressed that adrenomedullin or an agonist specific for adrenomedullin receptors might find a place in the treatment of cardiovascular disorders.

A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland

The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies.

GABA in the central amygdaloid nucleus modulates the electrolyte excretion and hormonal responses to blood volume expansion in rats

We investigated the involvement of GABAergic mechanisms of the central amygdaloid nucleus (CeA) in unanesthetized rats subjected to acute isotonic or hypertonic blood volume expansion (BVE). Male Wistar rats bearing cannulas unilaterally implanted in the CeA were treated with vehicle, muscimol (0.2 nmol/0.2 µL) or bicuculline (1.6 nmol/0.2 µL) in the CeA, followed by isotonic or hypertonic BVE (0.15 or 0.3 M NaCl, 2 mL/100 g body weight over 1 min). The vehicle-treated group showed an increase in sodium excretion, urinary volume, plasma oxytocin (OT), and atrial natriuretic peptide (ANP) levels compared to control rats. Muscimol reduced the effects of BVE on sodium excretion (isotonic: 2.4 ± 0.3 vs vehicle: 4.8 ± 0.2 and hypertonic: 4.0 ± 0.7 vs vehicle: 8.7 ± 0.6 µEq·100 g-1·40 min-1); urinary volume after hypertonic BVE (83.8 ± 10 vs vehicle: 255.6 ± 16.5 µL·100 g-1·40 min-1); plasma OT levels (isotonic: 15.3 ± 0.6 vs vehicle: 19.3 ± 1 and hypertonic: 26.5 ± 2.6 vs vehicle: 48 ± 3 pg/mL), and ANP levels (isotonic: 97 ± 12.8 vs vehicle: 258.3 ± 28.1 and hypertonic: 160 ± 14.6 vs vehicle: 318 ± 16.3 pg/mL). Bicuculline reduced the effects of isotonic or hypertonic BVE on urinary volume and ANP levels compared to vehicle-treated rats. However, bicuculline enhanced the effects of hypertonic BVE on plasma OT levels. These data suggest that CeA GABAergic mechanisms are involved in the control of ANP and OT secretion, as well as in sodium and water excretion in response to isotonic or hypertonic blood volume expansion.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

The effects of the menstrual cycle and hormonal contraceptives on the central thermoeffector threshold temperatures and width of the interthreshold zone

Basal body temperature (BBT) and thermoeffector thresholds increase following ovulation in many women. This study investigated if solely central thermoregulatory alterations are responsible. Seven females in a non-contraceptive group (NCG) were compared with 5 monophasic contraceptive users (HCG) on separate accounts: pre-ovulation (Trial I; d 2-5) and post-ovulation (Trial 2; 4-8 d post-positive ovulation) for NCG, and active phase for HCG (d 2-5, d 18-21). During immersion in 28°C water to the axilla, participants exercised for 20-30 min on an underwater ergometer. After steadily sweating, immersion continued until metabolism increased two-fold due to shivering. Rectal (Tre) BBT was not different between trials for neither NCG (1: 37.34±0.16°C; 2: 37.35±0.27°C) nor HCG. At exercise termination, Tre forehead sweating cessation increased (P<0.05) in trial 2 irrespective of group (1: 37.55±0.39°C; 2: 37.90±0,46°C). Tre shivering onset did not increase (P>0.05) in trial 2 (1: 36.91±0.50°C; 2: 37.07±0,45°C). The widths of the interthreshold zone increased (P<0.05) in trial 2 (1: 0.64±0.22°C; 2: 0.82±0.37°C) due to the increased sweating threshold only. HCG cooled quicker (1: -l.15±0,43°C; 2: -1.00±0.50°C) than NCG participants (1: - 0.58±0.22°C; 2: -0.52±O.29°C), and tympanic (Tty) sweat thresholds were significantly (P<0.05) decreased (1: 34.76±0.54°C; 2: 35.39±0.61°C) versus NCG (l: 35.57±0.77°C; 2: 35.89±1.04°C). Lastly, Tre and Tty thresholds were significantly different (P

Identificación del sexo y evaluación de la inducción hormonal en el Pejelagarto (Atractosteus tropicus)

Tesis (Maestría en Ciencias con Especialidad en Recursos Alimenticios y Producción Acuícola) UANL

Evaluation of Somaclonal Variation in Callus Cultures of Jatropha curcas Maintained on Different Hormonal Combinations Using RAPD Markers

Random genetic changes generated during in vitro culture are not desirable for plant micropropagation and genetic transformation. RAPD markers were used to detect the variation in leaf disc callus cultures of Jatropha curcas, maintained in Murashige and Skoog (MS) medium with different auxin and cytokinin combinations. In total 41 scorable bands were produced with 11 primers. Out of 41 bands, 37 were polymorphic (91.12%). The average number of polymorphic bands was 3.36 per primer. The highest similarity (0.82) with mother plant was seen in callus maintained on MS with hormonal combination Indole butyric acid - 0.4mg/l+ N6-benzyladenine purine - 4.0 mg/l. The callus grown on MS with hormonal combinations IBA- 0.4mg/l+ BAP- 2.0mg/l, IBA- 0.4mg/l+ BAP- 2.5mg/l and IBA- 0.6 mg/l+ BAP- 2.0 mg/l also showed similarity with the mother plant. Callus maintained on MS with hormonal combination IBA- 0.2mg/l+ BAP- 2.0 mg/l was found to show least similarity (0.53) with mother plant

Intervenção Farmacêutica na Contraceção Hormonal e de Emergência

O acesso aos métodos contracetivos hormonais regulares e de emergência configura para as mulheres a possibilidade de controlar a sua natalidade com elevada eficácia e segurança. A contraceção de emergência deve ser encarada como um método de recurso, a um método principal de contraceção. A sua disponibilidade representa um valioso recurso para as mulheres, ao permitir efetuar uma contraceção com elevado grau de eficácia e segurança após o coito. Devido ao aumento do consumo de contracetivos de emergência em Portugal, associado à possibilidade em adquiri-los sem intervenção farmacêutica, torna-se necessário perceber o perfil de consumo da contraceção de emergência. O farmacêutico devido à sua proximidade geográfica e permanente disponibilidade para com a população que serve, aliado ás suas competências na área do medicamento, assume cada vez mais uma importância crescente ao nível da contraceção hormonal. O recurso à contraceção de emergência representa em grande parte dos casos uma falha contracetiva ou a não utilização de métodos contracetivos durante o coito. O farmacêutico ao estar diretamente envolvido na dispensa de ambos os métodos tem a capacidade de com a sua intervenção melhorar as praticas contracetivas entre as mulheres portuguesas e contribuir para a utilização racional de medicamentos. Os objetivos do trabalho monográfico foram: efetuar uma revisão sobre métodos contracetivos hormonais incluindo os de emergência e respetiva intervenção farmacêutica em Portugal. Analisar o consumo e utilização da contraceção de emergência em Portugal. Neste contexto o trabalho desenvolvido consistiu numa revisão sobre os principais métodos contracetivos hormonais e de emergência. Realizou-se uma análise entre o consumo de contracetivos de emergência e a interrupção voluntaria da gravidez na tentativa de estabelecer uma relação entre ambos. Explorou-se a ideia da inclusão do farmacêutico na consulta de planeamento familiar e outros serviços em que este poderia representar uma mais valia para a população. Sugeriu-se uma intervenção ativa do farmacêutico em Portugal, com vista a promover a melhor utilização dos métodos contracetivos à disposição das mulheres. Relativamente à metodologia utilizada esta consistiu numa pesquisa bibliográfica com recurso ao motor de busca pubmed. Foram ainda realizados contactos com profissionais de saúde responsáveis pelo planeamento familiar, farmacêuticos comunitários, hospitalares, Infarmed, Ordem dos Farmacêuticos e suas homologas internacionais e industria farmacêutica, de modo a obter informações sobre a disponibilidade, consumo e utilização de contracetivos hormonais incluindo os de emergência. Concluiu-se que a contraceção hormonal oral é a forma de eleição entre as mulheres portuguesas, sendo por isso um ponto onde o farmacêutico comunitário deve estar particularmente atualizado. O aumento no consumo de contracetivos de emergência em 2010 sugere a dispensa sem intervenção farmacêutica. Não é possível estabelecer uma relação entre o consumo de contracetivos de emergência e a interrupção voluntaria da gravidez. A intervenção farmacêutica tem o potencial para melhorar a utilização dos métodos contracetivos entre as mulheres portuguesas.

Melatonin and the circadian entrainment of metabolic and hormonal activities in primary isolated adipocytes

The aim of this work was to investigate the effect of the in vitro circadian-like exposure to melatonin [in the presence or absence of insulin (Ins)] on the metabolism and clock gene expression in adipocytes. To simulate the cyclic characteristics of the daily melatonin profile, isolated rat adipocytes were exposed in a circadian-like pattern to melatonin added to the incubating medium for 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day) combined or not with Ins. This intermittent incubation was interrupted when four and a half 24-hr cycles were fulfilled. At the end, either during the induced night (melatonin present) or the induced day (melatonin absent), the rates of lipolysis and D-[U-(14)C]-glucose incorporation into lipids were estimated, in addition to the determination of lipogenic [glucose-6-phosphate dehydrogenase and fatty acid synthase (FAS)] and lipolytic (hormone sensitive lipase) enzymes and clock gene (Bmal-1b, Clock, Per-1 and Cry-1) mRNA expression. The leptin release was also measured. During the induced night, the following effects were observed: an increase in the mRNA expression of Clock, Per-1 and FAS; a rise in lipogenic response and leptin secretion; and a decrease in the lipolytic activity. The intermittent exposure of adipocytes to melatonin temporally and rhythmically synchronized their metabolic and hormonal function in a circadian fashion, mimicking what is observed in vivo in animals during the daily light-dark cycle. Therefore, this work helps to clarify the physiological relevance of the circadian pattern of melatonin secretion and its interactions with Ins, contributing to a better understanding of the adipocyte biology.

Investigating the Effects of Mifepristone (RU486) in the Behavioral, Hormonal and Central Responses to Acute Stress

Depression is associated with glucocorticoid hypersecretion, due to dysfunction of the hypothalamo-pituitary-adrenocorticol axis (HPA-axis). Because excess glucocorticoids are associated with depressive-like features in humans, glucocorticoid receptor antagonists are currently being tested for antidepressant efficacy in clinical trials. In the current study the hypothesis that mifepristone (RU486), a glucocorticoid receptor antagonist, would decrease the neuroendocrine and central HPA-axis responses to an acute stressor and attentuate depressive like behavior in an animal model of behavioral helplessness (forced swim test) was tested. Adult male rats were treated with 10 mglkg RU486 (subcutaneous) for five days and then exposed to a IO-minute forced swim test (FST), conducted in Plexiglas cylinders. FST sessions were videotaped for later analysis of behavioral immobility. Plasma ACTH and corticosterone CORT were measured at 15min and 90min after FST cessation. Animals were perfused and brains were collected for immunocytochemical assessment of c-Fos expression in the medial prefrontal cortex (mPFC), a brain region implicated in both depression and central control of the HPA axis. RU486 significantly decreased peak ACTH and CORT concentrations following FST exposure. In addition, glucocorticoid negative feedback was at1enuated in RU486-treated animals exposed to the FST. Exposure to FST alone induced c-FOS expression in the mPFC, as measured by the number of c-Fos positive neurons. Treatment with RU486 significantly increased the number of rnPFC c-Fos positive cell following FST exposure. The behavioral data obtained from FST paradigm, demonstrated that RU486 decreased immobility in the FST illustrating the potential efficacy of this drug as an antidepressant. Collectively these data suggest that RU486 dampens HPA-axis responses to stress, possibly by enhancing the excitability of stress-inhibitory neurons in the mPFC. This is particularly exciting, given the fact that this neural region is associated with decreased neural activity during depression in humans.