Chorionic gonadotropin as endogenous ligand for Toll-like proteins
Chorionic gonadotropin (CG) is actively involved in the immune processes during gestation. The hormone is known to realize its effects via LH/CG-receptor while activating protein kinase A. However, the presence of homologous sites in extracellular domains both of LH/CG-receptor and Toll-like proteins (TLR) allows suggesting yet another mechanism of CG action. The endogenous ligand for CG, in particular, could be the monocyte-expressed TLR4 molecule.
The aim of the work was to study the role of TLR4 and PKA in realization of CG effects on monocyte functioning. Prior to hormonal addition the monoclonal antibodies to TLR4 were introduced into the culture of fractionated monocytes obtained from women peripheral blood. Considering that the CG interaction with LH/CG-receptor results in PKA activation the PKA blocker H-89 was used in our work. Phagocytic activity of monocytes was evaluated by latex absorption, and the supernatants were used to determine the level of myeloperoxidase (MPO), elastase, cathepsin G. Cytokines (IL-6, IFN-, IL-1, and TNF-) were detected with immune enzyme method after the daily incubation in LPS presence.
Experimental approaches allowed determining that the hormone regulated the phagocytic activity of monocytes, as well as the secretion of IFN- and elastase via TLR4 molecules. At the same time, the hormonal modulation of MPO secretion was related to PKA activity that evidenced for the LH/CG-receptor involvement. Regarding the monocytic secretion of cathepsin G, IL-1, IL-6, and TNF- it was shown that CG realized its modulating effects both via TLR4 and LH/CG-receptor.
Thus, two key molecular mechanisms for CG effect realization exist at the monocytic level, such as classical mechanism via LH/CG-receptor and alternative one via TLR4 molecules. In a number of cases the hormone involved both TLR4 and LH/CG-receptor. The existence of different ways of hormonal signal realization could probably provide an explanation for diverse and differently directed effects of chorionic gonadotropin.