Endocrine Abstracts

It is well established that the interaction between an implanting embryo and the endometrium is essential for successful implantation and there is a variety of locally secreted factors within the uterine environment which underlies this maternal–fetal cross-talk. Human chorionic gonadotrophin (hCG) is a glycoprotein hormone secreted by the embryo and is essential during early stages of pregnancy to maintain progesterone production from the corpus luteum. Its receptor (LH/CGR), a G-protein coupled receptor (GPCR), is known to be expressed in the endometrium but the role of hCG and the underlying signalling mechanisms here are largely unknown. We show that the LH/CGR in human endometrial stromal cells (HESCs) acts via a Gαi pathway instead of the classical Gαs pathway and that signalling via this receptor may modulate important decidual-specific genes. We also observe a change in trafficking of the LH/CGR between the two cell–states of HESCs with control cells showing constitutive trafficking which is inhibited upon differentiation/decidualisation. However, the receptor is not visibly internalised following stimulation with hCG in undifferentiated or differentiated cells. This is specific to the LH/CGR as the same ‘switch’ in receptor trafficking is not observed with another classical GPCR, the β2-adrenergic receptor. We also show that a region of the C-terminal tail of the receptor dictates its endocytic trafficking, with more receptor localising to EEA1 positive early endosome compartments when this sequence is deleted. Furthermore, knockdown of the PDZ binding protein GIPC alters the endocytic trafficking of the WT receptor, re-routing it to larger endosomal compartments. These observations are consistent with LH/CGR trafficking in HEK293 cells, which primarily trafficks to an endosomal compartment upstream of early endosomes (pre-early endosomes). Dynamic alterations in the trafficking of the receptor in the endometrium may be an important regulatory mechanism in hCG actions on the endometrium during the crucial period of implantation.