Endocrine Abstracts

The hypothalamic paraventricular nucleus (PVN) is a major regulatory centre of energy homeostasis by possessing the unique capability of simultaneously controlling endocrine axes, water balance and autonomic functions. It receives neuronal information form orexigenic and anorexigenic cell groups of the basal hypothalamus that monitor peripheral metabolic signals (leptin, insulin, ghrelin, glucose, glucocorticoids) and also from brainstem centers relaying sensory information fr...

Introduction: Adenosine monophosphate-activated protein kinase (AMPK) is a regulator of cellular and systemic energy homeostasis. Many of the changes seen in glucocorticoid excess correspond to the metabolic steps regulated by AMPK. In the hypothalamus and adipose tissues, glucocorticoids and cannabiniods share the same tissue specific effects on AMPK activity. Cannabinoids have central orexigenic and peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). The ...

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gl...

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gl...

Type 1 cannabinoid receptor (CB1) is the principal receptor for endocannabinoids in the brain which mainly occurs in preterminal/terminal axons and mediates retrograde neuronal signaling mechanisms. A large body of physiological and electrophysiological evidence indicates the critical role of CB1 in the regulation of hypothalamic functions. Conversely, the distribution of CB1-containing axons in the hypothalamus is essentially unknown. Therefore, we have analyzed the distribut...

The pharmacological blockade of cannabinoid receptor type 1 (CB1) has been shown to counteract diet induced obesity (DIO). An unsolved question is whether the effects of CB1 blockade on energy balance are due to peripheral or central mechanisms. This is an important clinical issue since the CB1 antagonist drugs have recently been withdrawn from the market due to their psychiatric side effects, and novel drugs selectively acting at peripheral le...

We have previously shown that the orexigenic and peripheral adipogenic effects of ghrelin are mediated by its effect on the metabolic enzyme AMPK. As the cannabinoid (CB1)-antagonist rimonabant inhibits the orexigenic effect of ghrelin, we suggest that there is an interaction between cannabinoids and ghrelin.To study the involvement of CB1 in the effects of ghrelin, wild-type (WT) and CB1-knockout mice were treated with ghrelin and rimonabant.<p clas...

Objective: Serum TSH and thyroid hormone (TH) levels are routinely used as main measures of thyroid function. While these are highly valuable markers, it is becoming more evident that under specific conditions, their predictive power for tissue TH status is limited due to the highly complex nature of tissue-specific TH signaling. This led to a high demand for human tissue TH action markers that could allow the characterization of tissue TH economy. Therefore, our goal was to d...

Ghrelin, cannabinoids and glucocorticoids have all orexigenic and widespread metabolic effects. AMPK is a major controller of many metabolic processes. We have studied the effects of ghrelin and glucocorticoids and their interaction with endocannabinoids using cannabinoid-receptor-1 (CB1) knock-out mice and CB1 antagonist-treated mice, and using tissue samples from patients with Cushing’s syndrome and from a rodent model of Cushing’s syndrome. AMPK activity and downs...

Background: Excess glucocorticoids result in Cushing’s syndrome (CS) which is characterised by increased food intake, central obesity, dyslipidaemia and insulin resistance, leading to the metabolic syndrome. AMPK is a regulator of energy homeostasis and plays an important role in the regulation of appetite, glucose uptake, lipogenesis and gluconeogenesis. We hypothesised that the effects of corticosteroids on metabolism would be mediated by changes in AMPK activity in a t...