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 lymphocyte-suppressive medications compared to that in age-matched controls. In vitro, however, neither tacrolimus nor cyclosporin A reduced dehydroepiandrosterone (DHEA) release by adrenocortical cells. Therefore, we examined the potential role of lymphocytes in adrenal androgen production, using cocultures of human T lymphocytes and adrenocortical primary or transformed cells. Co-cultures led to a 4-fold elevation of DHEA levels (490.4 +/- 94.8% over basal), which was greater than the increase observed after the addition of maximal concentrations of ACTH (117.4 +/- 14.8%). Separation of cells by semipermeable membranes abolished this effect, and transfer of leukocyte-conditioned medium had little androgen-stimulating effect. These data suggested that the observed stimulation of androgen secretion required cell contact rather than soluble paracrine factor(s). Furthermore, we examined human adrenal glands for the presence of T lymphocytes and contact between these cells and steroid-secreting cells of the zona reticularis. Indeed, T lymphocytes expressing CD4 and CD8 antigens were present within human adrenal zona reticularis by immunohistochemical subtyping. Electron microscopic analyses demonstrated direct cell-cell contact between T lymphocytes and adrenocortical cells in situ. This study provides evidence for a novel mechanism of immune-endocrine interactions of direct T lymphocyte-adrenocortical cell contact-mediated stimulation of adrenal androgen secretion.
Wolkersdörfer
G W
GW
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. WolkersdoerferG@netscape.net
Lohmann
T
T
Marx
C
C
Schröder
S
S
Pfeiffer
R
R
Stahl
H D
HD
Scherbaum
W A
WA
Chrousos
G P
GP
Bornstein
S R
SR
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002450:Cell Communication; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003687:Dehydroepiandrosterone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D015385:Zona Reticularis / Q000166:cytology* / Q000502:physiology
D000728:Androgens; D017077:Culture Media, Conditioned; D010835:Phytohemagglutinins; D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone