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Overview and significance of Immune-endocrine interactions in the regulation of Leydig cell function Mitochondrial vs. Nuclear control of steroidogenesis cAMP ROS cytokines Acute regulation at the level of substrate availability + PKA + + testosterone - Chronic regulation at the level of gene transcription Steroidogenic machinery Sites of immune inhibition ROS Relevance to female reproduction? • Normal physiological states: ovulation, menstruation, implantation, fetal-maternal interactions, parturition, and nursing all involve aspects of immune-endocrine cooperation • LPS injection inhibits ovarian steroidogenesis H2O2 effects on luteal cells • Behrman et al. have shown H2O2 blocks cholesterol transfer inhibits 3b-HSD – Behrman HR, Aten RF. Endocrinology 1991;128(6):2958-66 • Carlson et al. have shown H2O2 causes lipid peroxidation – Carlson JC, et al. Free Radic Biol Med 1993;14(1):79-84 • Reactive oxygen generated by leukocytes may contribute to luteolysis and initiate apoptosis Sexual dichotomy of immune responses • Females are more susceptible to autoimmune diseases than males • Estradiol and prolactin are both immunostimulatory • Testosterone is immuno-inhibitory Conclusions • Inflammation and infection may contribute to, or cause decreased male reproductive function • There is a push-pull system between the immune and endocrine systems – During times of sickness the immune system suppresses the reproductive system (testosterone production) – During times of normal health testosterone suppresses the immune response Antechinus Stuartii victim of his own testosterone Hales Lab Beth Nardulli Salil Ginde John Allen Thorsten Diemer John Choi Karen Held Hales NIH: HD25271 HD35544 collaborators Bruce Bosmann Barbara Clark Jim Ferguson Lester Lau Jean-Guy LeHoux Mark McLean Yossi Orly Keith Parker Anita Payne Richard Pestell Catherine Rivier Focko Rommerts Douglas Stocco Navigation to other presentations Immune-endocrine control of Leydig cells Cytokine control of steroidogenesis The role of AP-1 Cytokine signaling
