Transcript Overview and significance of Immune

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