Neurobiology and Hormonal Control of Lacrimal and Salivary Gland Function

Abstract

Sjogren's syndrome (SS) is characterized by diminished production of secretes from exocrine glands and sicca complex, which occur in an autoimmune context; 90\% of patients are women, usually developing the disease when they are 40-50 years old. This characterization comprises several neuroimmunoendocrine aspects. The sympathetic, parasympathetic, vascular, acinar, and myoepithelial systems normally work in a co-ordinated fashion in two phases, resting and stimulated phases, corresponding to the secretion of resting and stimulated saliva. Stimulation of the exocrine flow with acetylcholine is coupled with a proportional local release of acinotrophic vasoactive intestinal peptide (VIP) from post-ganglionic parasympathetic nerve terminals, which helps to recover and repair the acinar cell during the ``resting{''} (recovery) phase. Lost (dead and detached) acinar cells are replaced by remodeling based on an asymmetric division of the intercalated duct progenitor cells, which as a result are able to maintain their unipotent sternness and at the same time able to replace the lost acinar cells. This remodeling is maintained by dehydroepiandrosterone (DHEA) produced in the reticular zone of the endocrine adrenal gland in an endocrine process, but is locally in exocrine glands converted to dihydrotestosterone (DHT) in an intracrine process. SS is characterized by deranged intracrine enzymatic machinery and impaired DHEA-to-DHT conversion. This impairment leads particularly in women to acinar cell atrophy/loss and a reciprocal ductal cell hyperplasia. Men are protected because they feed the intracrine machinery also with testosterone, only one step away from DHT. Abnormally processed self antigens are released from dying cells and break the immunologic tolerance so that autoantibodies are formed against previously hidden endotopes. Immune inflammation leads to synthesis and release of tumor necrosis factor-alpha, interleukin-1 beta, and other cytokines, which impair signal transduction in acinar cells and add to the burden of the inflammatory functio laesa.