Figure 8
A diagrammatic representation of the overall results showing various signalling molecules modulated downstream of LH/CGR activation regulating genes associated with steroidogenesis during different functional status in the monkey CL. (A) The diagram describes activation of the well characterized LH-mediated canonical pathway LH/CGR/Gαs/AC/cAMP/PKA/(pCREB, SF-1/LRH-1) in the monkey CL, during mid luteal phase (when the CL function is high) leading to increase in SR-B1 gene expression (both mRNA and protein levels) and in turn higher serum P4 levels. Further, it also illustrates prevention of SFKs activation and lower cAMP-PDE activity in presence of LH during mid stage of luteal phase, inturn avoiding modulation of LH/CG responsiveness by the molecular modulators [pSrc (Y-416) and PDE4D]. (B) The diagram demonstrates decrease in LH-mediated inhibition of SFKs activation and further increase in both SFKs phosphorylation and cAMP-PDE activity in the monkey CL during spontaneous luteolysis or PGF2α-induced luteolysis (CL function is low) leading to modulation of LH/CG responsiveness in turn resulting in lower circulating P4 levels. (C) To determine the role of LH in regulation of SFKs activity, LH withdrawal using GnRH-R antagonist (CET) was performed. The diagram describes the elimination of LH-mediated activation of canonical signalling and increase in both SFKs phosphorylation and cAMP-PDE activity in the monkey CL during CET-induced luteolysis (CL function is low) leading to decrease in SR-B1 gene expression and in turn lower circulating P4 levels. (D) To determine the role of LH in regulation of SFKs activity, simulation of early pregnancy condition was developed and LH replacement in CET treated animals to rescue CL function was performed. The diagram illustrates recurrence of LH/CG-mediated cAMP/PKA/pCREB signalling and suppression of SFKs activation leading to lower cAMP-PDE activity, higher SR-B1 gene expression and in turn higher circulating P4 levels.