oxytocin and Acquired-Immunodeficiency-Syndrome

Oxytocin receptors (OTRs) are expressed in numerous tissues, including human normal endothelium. Here we investigated the expression and biological significance of OTRs in Kaposi's sarcoma (KS), an intensely angioproliferative disease of possible vascular origin with a prominent inflammatory component. Immunohistochemistry and in situ hybridization studies showed OTR expression in tumor cells of cutaneous classic and AIDS-related KS lesions. OTR mRNA and protein were also detected on cultured KS-IMM spindle cells by reverse transcription-PCR and immunofluorescence procedures. In these cells, OTR expression was up-regulated by the supernatants of resting CD4+ and CD8+ lymphocytes through a still unidentified factor. Functionality of OTRs was demonstrated because OT treatment of KS-IMM cells led to a significant increase in cell proliferation, coupled to the increase of intracellular calcium, but did not effect cell migration in vitro or angiogenesis in vivo. In addition, we demonstrated that CD4+ and CD8+ cells produce OT themselves, thus constituting an intralesional source of peptide. These results indicate that: (a) functioning OTRs are expressed in KS cells and modulated by the inflammatory counterpart of KS lesions; (b) via OTRs, OT stimulates KS-IMM cell proliferation and could, therefore, be considered a new possible relevant growth factor involved in KS progression; and finally (c) the evidence of OT synthesis by CD4+ and CD8+ lymphocytes strongly suggests the existence of local endocrine-immunological cross-talk in Kaposi's sarcoma.

Topics: Acquired Immunodeficiency Syndrome; Calcium; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Cell Movement; Humans; Interleukins; Neovascularization, Pathologic; Oxytocin; Receptors, Oxytocin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoma, Kaposi; Tumor Cells, Cultured

Recently, a 40% reduction in the total of oxytocin immunoreactive neurons of the paraventricular nucleus of the hypothalamus in AIDS patients was reported. In the present study, we determined whether this decrease is associated with a diminished amount of oxytocin mRNA. We used in situ hybridization combined with densitometric image analysis for the quantitative assessment of oxytocin gene expression in the paraventricular nucleus of a group of AIDS patients (n=10) and a carefully matched control group (n=8). We found no significant difference (P=0.08) in the amount of oxytocin mRNA per total paraventricular nucleus between the two groups. In addition, no significant differences were found in the part of the volume of the paraventricular nucleus that was occupied by hybridized cells (P=0.12) or in the mean signal density (P=0.08). The findings do not support the hypothesis that the extensive decrease in oxytocin immunoreactive neurons of the paraventricular nucleus in AIDS is associated with a decrease in total oxytocin mRNA content in this nucleus. The data are compatible with the suggestion that in AIDS the biosynthesis of oxytocin is changed in an unknown way at the (post)transcriptional level.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Case-Control Studies; Female; Humans; In Situ Hybridization; Male; Middle Aged; Oxytocin; Paraventricular Hypothalamic Nucleus; Reproducibility of Results; RNA, Messenger

Topics: Acquired Immunodeficiency Syndrome; Case-Control Studies; Gene Expression; Humans; In Situ Hybridization; Oxytocin; Paraventricular Hypothalamic Nucleus; RNA, Messenger

The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age range 25-62 years), four of whom had a probable HIV-1 associated dementia complex, and six non-demented heterosexuals (four males and two females, age range 21-73 years). Ten males without a primary neurological or psychiatric disease served as a control group. The number of OXT-expressing neurons in the paraventricular nucleus of both groups of AIDS patients was approximately 40% lower than that of the controls. In contrast, the three groups showed no significant differences in the number of AVP-expressing neurons in the paraventricular nucleus. Since there were no significant differences in the number of AVP and OXT cells between the homosexual and heterosexual subjects with AIDS, the morphological difference in the paraventricular nucleus seems to be related to AIDS and not to sexual orientation. No inflammatory changes were found in the paraventricular nucleus area. The selective changes in the OXT neurons of the paraventricular nucleus may be the basis for part of the neuroendocrine, autonomic dysfunction or vegetative symptoms in AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Arginine Vasopressin; Female; Humans; Male; Middle Aged; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Sexual Behavior