Fig. 5.

Schematic representation of hypothetical model describing endocrine cascades in human feto-placental unit. Near term, placenta-derived CRH increases and directly stimulates HFA production of DHEA/DHEAS and cortisol. Increased cortisol, in turn, stimulates production of placental CRH. CRH also up-regulates expression of the ACTHR, thereby increasing HFA responsiveness to ACTH, the level in fetal circulation of which may be constant or decrease near term. HFA and placental CRH constitute positive feedback cascade. DHEA/DHEAS is converted by placenta to estrogen, promoting initiation of parturition partly through up-regulation of contraction-associated proteins. Cortisol also promotes maturation of fetal organs (e.g., the lung) and stimulates production of prostaglandins, uterotonins necessary for parturitional processes. CRH also directly promotes initiation of parturition in part by increasing prostaglandins. When “functional withdrawal” of progesterone occurs, coupled with these changes, parturition is initiated.