Aspectos neuroendócrinos da síndrome metabólica

Abstract

Arq Bras Endocrinol Metab vol 47 nº 4 Agosto 2003 410 RESUMOA síndrome metabólica (SM) é caracterizada por alterações no metabolismo glicídico, obesidade, hipertensão e dislipidemia. Estas alterações metabólicas interrelacionam-se com diversos eixos endócrinos controlados pelo hipotálamo e pela hipófise. A obesidade central parece relacionar-se a uma hiperativação do eixo hipotálamo-hipófise-adrenal, como também do sistema nervoso simpático, que poderia levar a um quadro de hipercortisolismo sub-clínico e hipertensão arterial. A SM é também um estado de hipo-somatotropismo relativo relacionado à gordura visceral. Além disso, níveis elevados de ácidos graxos livres e a hiperinsulinemia, secundários à resistência insulínica, estão relacionadas a um bloqueio do eixo somatotrófico. Em homens, a SM relaciona-se a um hipogonadismo tanto por diminuição de gonadotrofinas como por inibição direta da produção de testosterona. Já nas mulheres, existe um excesso de produção de androgênios, principalmente relacionado à hiperinsulinemia, aumento da atividade da aromatase e da liberação de LH. Desta forma, a SM é um estado relacionado a importantes modificações nos mecanismos de feedback responsáveis pelo correto funcionamento dos eixos neuroendócrinos. The metabolic syndrome (MS) is characterized by alterations in carbohydrate metabolism, obesity, hypertension and dislipidemia. These metabolic alterations interfere with some endocrine axes controlled by the hypothalamus and the pituitary. Central obesity might be associated to a state of subclinical hypercortisolism and hypertension, secondary to an activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. MS is also a state of relative hyposomatotropism, probably related to visceral fat. Furthermore, high levels of free fat acids and hyperinsulinemia, secondary to insulin resistance, can contribute to a blockade of the somatotropic axis. In men, MS is related to a state of hypogonadism caused by impairment in gonadotropin secretion and testosterone production. Women exhibit excessive androgen production, secondary to hyperinsulinemia, high levels of LH and to an increase in aromatase activity. In summary, MS is a condition linked to important modifications in feedback mechanisms responsible for the correct functioning of the neuroendocrine axes.

Relationship between insulin and hypogonadism in men with metabolic syndrome

“…The reasons for the association between metabolic syndrome and hypogonadism are not completely clear. It has been suggested that insulin resistance, acting through signs mediated by the adipose tissue, including increased levels of leptin, would have a direct role in the regulation of gonadal function, thus decreasing the concentrations of testosterone (1,4,25,26). At the same time, pro-inflammatory cytokines, such as TNF alpha, IL-1 and IL-6, produced by visceral adipocytes, are also associated with insulin resistance (27,28).…”

“…This would inhibit gonadotrophin production centrally, and further decrease testosterone levels. Subsequently, the decrease in testosterone would facilitate a higher deposition of body fat and a more severe degree of hypogonadism (1,7,44).…”

“…It is characterized by alterations in carbohydrate metabolism, obesity, systemic arterial hypertension and dyslipidemia (1).…”

“…In the gonado-trophic axis, metabolic syndrome is associated with a state of male hypogonadism, whose origin and precise physiopathological mechanisms are still unknown (1,4).…”

“…However, the free testosterone levels may remain normal or reduced, depending on the severity of obesity (1)(2)(3). Several theories have been proposed to explain the decrease in the total and free testosterone levels, including the direct inhibition of testicular production by insulin and leptin, elevation of estrogen concentrations and alteration in the secretion of gonadotrophins (1,(4)(5)(6)(7).…”