Λουτράδης Δημήτριος, Καθηγητής, Ιατρική, ΕΚΠΑ
Καλλιανίδης Κωνσταντίνος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Δρακάκης Πέτρος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
CRH (Corticotrophin Releasing Hormone) is a 41 amino acid neuropeptide, firstly isolated from sheep hypothalamus. CRH is basicly implicated in the regulation of the secretion of ACTH (Adrenocorticotropic hormone) from pituitary gland and is widely dispersed in the brain, thus orchestrating endocrinological and behavioral Autonomous Nervous System (ANS) responses to stress. Of note, CRH acts additionally as mediator among immune, neurological and endocrinological system.
Besides its distribution to brain, CRH is localized to adrenal gland, human lymphocytes, inflammatory foci, placenta, uterus, ovary, corpus luteus, trophoblast and endometrium.
CRH tranduces signals via its two receptors, CRH-R1 and CRH-R2, which are members of G-proteins superfamily, and are expressed by two separate genes. Studies in mouse embryos at the developmental stage of morulla and blastocyst demonstrated to express only CRH-R1 and not CRH-R2.
During implantation phase, the endometrium responds immunologically to the penetrating blastocyst. This immunologic response is characterized as acute, aseptic inflammatory response. Nevertheless, embryo suppresses this inflammatory response, preventing the miscarriage. It has been shown that trophoblast cells and lutenized cells secrete CRH and express the ligand of a proapoptotic cytokine Fas (CD95). In vitro findings depicted that while R1 receptor is blocked by a well- known antagonist, antalarmin, embryo penetration enhances by 60%.
To this extend, CRH exerts a protective role in embryo against mother’s immune response by establishing immune T cell tolerance mediated by Fas/ FasL interactions. In vivo studies exhibited that mice administered with antalarmin have dominantly reduced implantation sites by 70% and dampened FasL expression. Thus, non functional CRH/ CRH-R1 axis is responsible for recurrent miscarriages, preeclampsia and placental incontinence.
This study was conducted with the aim of detecting CRH-R1 and R2 transcripts in human blastocysts, in the frame of continuing or verifying earlier studies that demonstrated the expression of CRH-R1 and not CRH-R2 mRNA in mouse embryos at morulla and blastocyst developmental stage. This scientific question was approached by using molecular biology techniques, such as RNA extraction and cDNA synthesis from human bastocysts and then CRH-R1 and R2 identification by Real Time PCR using random hexamers.
Data suggest a trans-species CRH-R1 detection in transcriptional level, since R1 receptor was identified in the blastocyst specimens. On the other hand, there weren’t detected any CRH-R2 transcripts, corroborating previous studies. To sum up, the results are indicative of the possible role of CRH/ CRH-R1 axis in pre-implantation stages of the human blastocyst and confirms that this axis is conserved in mammals and specifically in human and mouse.
CRH, CRH-R1, CRH-R2, Cortico releasing hormone, Human blastocyst, Implantation, Stress luck of implantation