Non-Reproductive Effects of Estradiol: Hydromineral Homeostasis Control

The hydromineral homeostasis is fundamental to survival due to maintenance constant the osmotic properties of the plasma and proper tissue perfusion pressure, being maintained primarily through the regulation of the ingestion and urinary excretion of water and electrolytes, mainly sodium. The Renin-Angiotensin System (RAS) plays an essential role in the maintenance of hydromineral homeostasis by eliciting sodium and water intake and by inducing sodium urinary retention through aldosterone release and hemodynamic effect via angiotensin II a key component of the RAS. The hypothalamus-pituitary system also plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin (AVP) and oxytocin (OT) in response to osmotic and non-osmotic, and volemic stimuli. Furthermore, some studies report that besides reproductive function and sexual behavior, ovarian gonadal hormones, mainly 17β-estradiol (E2), modulate other non-reproductive functions such as cardiovascular system, body fluid balance, mood, mental state, memory, and cognition. Estradiol is known to mediate hydromineral homeostasis and blood pressure mainly by attenuating RAS actions. On the other hand, estradiol modulates neurohypophysial hormones secretion in many different ways. In this chapter, we will discuss the main non-reproductive effects of E2 on the control of hydromineral homeostasis, focusing on ingestive behavior and neurohypophyseal hormonal release

Primary adrenal insufficiency in adults: 150 years after Addison

Thomas Addison first described, 150 years ago, a clinical syndrome characterized by salt-wasting and skin hyperpigmentation, associated with a destruction of the adrenal gland. Even today, over a century after Addison's report, primary adrenal insufficiency can present as a life-threatening condition, since it frequently goes unrecognized in its early stages. In the 1850 s, tuberculous adrenalitis was present in the majority of patients, but nowadays, autoimmune Addison's disease is the most common cause of primary adrenal insufficiency. In the present report, we show the prevalence of different etiologies, clinical manifestations and laboratorial findings, including the adrenal cortex autoantibody, and 21-hydroxylase antibody in a Brazilian series of patients with primary adrenal insufficiency followed at Divisão de Endocrinologia da Universidade Federal de São Paulo (UNIFESP) and at Faculdade de Medicina de Ribeirão Preto - USP (FMRP-USP).Thomas Addison descreveu pela primeira vez, há 150 anos, uma síndrome clínica de perda de sal em indivíduos com hiperpigmentação cutânea, associada à destruição da glândula adrenal. Atualmente, a insuficiência adrenal ainda representa uma condição de risco, pois seu diagnóstico é freqüentemente não reconhecido nas fases iniciais da doença. A adrenalite tuberculosa era a causa mais freqüente na maioria dos casos descritos inicialmente, mas, na atualidade, a doença de Addison auto-imune está presente em uma grande porcentagem de pacientes com insuficiência adrenal primária. No presente trabalho, apresentamos a prevalência das diferentes causas, manifestações clínicas e achados laboratoriais, incluindo a determinação de anticorpos anticórtex adrenal e anti-21-hidroxilase em pacientes acompanhados com insuficiência adrenal primária seguidos nos Ambulatórios das Divisões de Endocrinologia da Universidade Federal de São Paulo (UNIFESP) e da Faculdade de Medicina de Ribeirão Preto - USP (FMRP-USP).Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica MédicaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de FisiologiaUNIFESPSciEL

PI3K p110β subunit in leptin receptor expressing cells is required for the acute hypophagia induced by endotoxemia

Objective: Hypophagia and increased energy expenditure under inflammatory conditions, such as that observed after bacterial lipopolysaccharide (LPS) administration, are associated with leptin secretion. The hypophagic effect of leptin depends in part on the activation of PI3K signaling pathway. However, the role of PI3K in the endotoxemia-induced hypophagia has not been determined. Methods: In an attempt to examine the functional contribution of the PI3K pathway in hypophagia and weight loss induced by LPS (100 ug/Kg, ip), we performed a central pharmacological PI3K inhibition (LY294002). Additionally, to gain mechanistic insights on the role of the catalytic PI3K p110α subunit in leptin responsive cells, mice expressing Cre-recombinase driven by the Lepr promoter (LepR-Cre) were crossed with mice carrying a loxP-modified p110α allele (Pi3kca gene) (LepRΔp110α). As studies have suggested that the PI3K p110β subunit has a dominant role over p110α in energy homeostasis, we further crossed LepR-Cre mice with loxP-modified p110α and p110β (Pi3kcb gene) alleles (LepRΔp110α+β). In order to verify the requirement of leptin in PI3K effects on food intake, we also used leptin-deficient ob/ob mice. Results: We found that LPS stimulates PI3K and STAT3 signaling pathways in cells expressing the leptin receptor. Central PI3K inhibition prevented LPS-induced hypophagia and weight loss. Genetic deletion of p110α subunit selectively in LepR cells had no effect on LPS-induced hypophagia and weight loss. However, p110α and p110β double deletion in LepR cells prevented LPS-induced hypophagia and partially reversed the weight loss. Leptin deficiency blunted LPS-induced acute pAKT and pSTAT3 phosphorylation and the acute suppression of food intake. Conclusions: Our studies show that the PI3K p110β subunit in LepR cells is required for acute endotoxemic hypophagia. The data provide promising approaches for PI3K inhibition in preventing low energy balance and cachectic states during inflammatory challenges. Keywords: LPS, Metabolism, Leptin, Hypothalamus, Inflammatio