Previous and Current Research
1. Intercellular Interactions in the Endocrine System
One focus of our research is defining basic mechanisms and clinical implications of cellular crosstalk in endocrine tissues. The adrenal gland comprises two endocrine tissues of distinct origin, the catecholamine-producing medulla and the steroid-producing cortex. Using the adrenal gland as a model we have demonstrated that tissue integrity, input from the nervous system or intercellular communication is essential for the normal functioning of the gland and the adequate respond to the homeostatic challenges of stress. We have demonstrated that intact intraglandular cellular interactions are required for normal development, differentiation and zonation of the adrenals and that alterations in intercellular communication, local production of neuropeptides, growth factors and cytokines, and aberrant expression of ectopic receptors are implicated in adrenal hyperplasia, autonomic hormone production and tumour formation.
In ongoing research, we are now focussing on the involvement of these intraglandular cellular interactions in the development of adrenomedullary neuroendocrine cells from neural crest-derived proliferation competent cells.
2. Endocrine Function of Adipose Tissue
In Westernized countries overweight and obesity have reached epidemic proportions with dramatic medical consequences. Obesity is a major risk factor for lipid abnormalities, atherosclerosis, type 2 diabetes mellitus, certain types of cancer, and high blood pressure. The adipocyte has long been suggested to be directly involved in the body’s homeostasis and recent evidence now proves that adipose tissue is a highly active endocrine organ. We therefore test the hypothesis that adipose secretory factors directly influence the body’s endocrine system and consequently are responsible for some of the medical problems associated with overweight. Indeed, factors (adipotensins) secreted from human adipocytes directly stimulate adrenal steroidogenesis, with the most prominent effect on aldosterone secretion. Adipocytes can influence adrenal function in an endocrine manner via secretion into the blood stream or in a paracrine manner due to the fact that adipocytes are regularly located within the adrenal gland. These data indicate that adipocytes directly stimulate adrenal aldosterone secretion, the body’s most potent mineralocorticoid and therefore might be responsible for obesity hypertension.
In ongoing studies we are now:
1. Characterizing the factors responsible for this stimulation.
2. Identifying the signalling pathways involved in the adipocyte mediated aldosterone secretion
3. Immune Function of Endocrine Tissue
Some obesity-related diseases such as atherosclerosis and type 2 diabetes mellitus have an inflammatory background and can be triggered by inflammation. Adipose tissue is able to produce inflammatory cytokines.
We therefore test the hypothesis that adipose tissue has specialized receptors (Toll-like receptors) that activate the innate and the adaptive immune system. Changes in the Toll-like receptor expression seem to be directly involved in the body’s homeostasis and might therefore be responsible for some of the medical problems associated with overweight. In the ongoing project we characterize the expression of Toll-like receptors and proinflammatory cytokines in adipocytes and the role of Toll-like receptors in the regulation of cytokine release.
In a second project, the expression and function of Toll-like receptors is investigated in the adrenal cortex. Glucocorticoids produced by the adrenal glands are known to hamper inflammatory processes and contribute to homeostasis after bacterial clearance. Toll like receptors are major pathogen recognising molecules and regulate immune response. Adrenal Toll-like receptors are suggested to also influence steroidogenesis and thereby directly link adrenocortical function to bacterial infection.