The Progestin-Only Contraceptive Medroxyprogesterone Acetate, but Not Norethisterone Acetate, Enhances HIV-1 Vpr-Mediated Apoptosis in Human CD4+ T Cells through the Glucocorticoid Receptor

摘要: The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of GR. Glucocorticoids (GCs) Vpr have been reported to induce apoptosis in various cells, T-cells. We previously shown that injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial full agonist for GR, unlike norethisterone (NET-A). investigated functional cross talk between GR inducing CD4+ T-cells, absence presence GCs these progestins, as well progesterone. By using flow cytometry, we show that, contrast NET-A progesterone, synthetic ligand dexamethasone (Dex), cortisol MPA primary Furthermore, C-terminal part peptide, or pseudovirus, together with Dex further increased apoptotic phenotype, combination Western blotting, PCR use receptor- selective agonists, provide evidence estrogen are only steroid receptors expressed peripheral blood mononuclear cells. These results, findings RU486, antagonist, prevents Dex-, MPA- Vpr-mediated apoptosis, first time agonists increase T-cells via induction involves differential expression key genes by both GCs/MPA. This work suggests contraceptive doses but not progesterone could potentially accelerate depletion GR-dependent fashion positive women, thereby contributing immunodeficiency. results imply choice progestin used contraception may be critical susceptibility progression diseases such HIV-1.