Lymphocytes stimulate dehydroepiandrosterone production through direct cellular contact with adrenal zona reticularis cells: A novel mechanism of immune-endocrine interaction

Adrenal androgen production was reduced by 80% in patients receiving T lymp hocyte-suppressive medications compared to that in age-matched controls. In vitro, however, neither tacrolimus nor cyclosporin A reduced dehydroepiand rosterone (DHEA) release by adrenocortical cells. Therefore, we examined th e potential role of lymphocytes in adrenal androgen production, using cocul tures of human T lymphocytes and adrenocortical primary or transformed cell s. Cocultures led to a 4-fold elevation of DHEA levels (490.4 +/- 94.8% ove r basal), which was greater than the increase observed after the addition o f maximal concentrations of ACTH (117.4 +/- 14.8%). Separation of cells by semipermeable membranes abolished this effect, and transfer of leukocyte-co nditioned medium had little androgen-stimulating effect. These data suggest ed that the observed stimulation of androgen secretion required cell contac t rather than soluble paracrine factor(s). Furthermore, we examined human a drenal glands for the presence of T lymphocytes and contact between these c ells and steroid-secreting cells of the zona reticularis. Indeed, T lymphoc ytes expressing CD4 and CD8 antigens were present within human adrenal zona reticularis by immunohistochemical subtyping. Electron microscopic analyse s demonstrated direct cell-cell contact between T lymphocytes and adrenocor tical cells in situ. This study provides evidence for a novel mechanism of immune-endocrine interactions of direct T lymphocyte-adrenocortical cell co ntact-mediated stimulation of adrenal androgen secretion.