Section of Endocrinology, Children's Mercy Hospital, University of Missouri-Kansas City
School of Medicine, Kansas City, Missouri 64108, USA
The hypothalamic homone gonadotropin-releasing hormone (GnRH)
displays gender-specific actions. Pituitary responsiveness to
GnRH is generally increased by estrogens and decreased by androgens.
GnRH is now known to be produced by the immune system and to
exert potent immunologic actions. Our central hypothesis is
that gender differences in responsiveness to GnRH in the immune
system play a pivotal role in the gender differences in immunity
and autoimmunity. Studies in lupus-prone mice demonstrate that
gnrh exacerbates murine lupus in a gender-specific fashion.
Subsequent studies from our laboratory suggest that the gender
differences in immunologic responsiveness to GnRH may relate
to differences in the expression of the signal transducers through
which GnH acts namely, the G proteins, GS, and GQ/11. We have
further demonstrated gender differences in second messengers
for GnRH, IP3, and camf in immune cells. we have also demonstrated
that GnRH agonist increases the quantities and/or activity of
G proteins in immune cells in a gender-specific fashion. we
speculate that gender differences in GnRH production and action,
and in g protein expression play a role in a variety of autoimmune
diseases that affect females predominantly.
