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CAVEAT LECTOR
CORTICOTROPIN RELEASING HORMONE (CRH) IN NORMAL AND PREGNANT UTERUS: PHYSIOLOGICAL IMPLICATIONS
Zoumakis E, Makrigiannakis A, Margioris A, Stournaras C, Gravanis ADepartments of Pharmacology, Clinical Chemistry, Biochemistry, Medical School, University of Crete, Iraklion 71110, Greece
Received 11/2/95; Accepted 12/14/95; On-line1/1/96
6. CRH IN THE PREGNANT UTERUS
6.1 Placenta
Multiple sites within the pregnant uterine cavity express the CRH gene, including the trophoblasts, fetal membranes (chorion, amnion) and decidua. The trophoblastic syncytium appears to be the major source of uterine CRH. Plasma CRH in pregnant women, the source of which is placenta, undergoes a sharp increase during the third trimester of pregnancy. Thus, placental CRH increases progressively during pregnancy with a time course similar to that of ir-CRH in maternal plasma. The CRHBP is also produced by placenta and intrauterine tissues and may represent one of the major mechanisms to control CRH activity during pregnancy (34-42).
Glucocorticoids positively regulate CRH gene in human placenta (41) in contrast to their suppressive effects in hypothalamus. Cytokines have a stimulatory effect on placental CRH. Indeed, IL-1 is present in human placenta, stimulating placental CRH secretion. Cytokines also stimulate the release of placental PGE2 and PGE2a which in turn stimulate CRH and ACTH secretion. On the other hand, glucocorticoids inhibit the production of cytokines, possibly counterbalancing their direct stimulatory effect on placental CRH production (34,47).
The role of placental CRH in maternal-fetal physiology is unknown. Since it is secreted into both maternal and fetal circulation, it could function to influence the HPA axis of either mother or fetus, providing an additional adaptation mechanism of the maternal HPA axis to the demands of pregnancy and regulating the growth of fetal adrenals. It is also postulated that CRH participates at the initiation of labour regulating myometrial contractility by increasing the release of intrauterine prostaglandins and by sensitising myometrium to oxytocin (35,46).
6.2 Decidua
Ir-CRH and CRH mRNA are present in human decidua and in the "in vitro" decidualized stromal endometrial cells (48). There is a gestational age-related increase in decidual mRNA levels.