The luteinizing hormone (LH) receptor is
fundamental for the regulation of the corpus luteum
(CL) in women and non-human primates. Its ligands,
LH and human chorionic gonadotropin (hCG), have key
roles in the regulation of tissue and vascular remodeling
associated with luteal formation and regression.
However this remodeling involves the regulation of
cells that do not express LH receptors including
endothelial cells, pericytes, fibroblasts and
macrophages. We have taken a candidate molecule
approach to identify important LH/hCG-regulated
paracrine molecules and their receptors in CL and assess
the effects of their manipulation in vivo and in vitro.
Vascular endothelial growth factor (VEGF) acts on
endothelial cells and is a major paracrine regulator of
luteal angiogenesis and vasculature maintenance.
Luteolysis is associated with increased SLIT/ROBO,
connective tissue growth factor (CTGF) and matrix
metalloproteinase (MMP) expression in luteal
fibroblasts. Investigation of the inhibition of these
changes by hCG has identified activin A as a novel
paracrine luteolysin and locally generated cortisol as a
novel paracrine luteotropin. The molecular regulation of
luteal function in the primate is complex and the
paracrine regulation of luteal function is still not fully
understood. Locally, the luteolytic activities of
SLIT/ROBO and activin-A are inhibited by hCG and
the luteotropic activities of VEGF and cortisol are
stimulated by hCG.
