In addition, certain antiprogestins are known to exert antiglucocorticoid activity upon the adrenocorticotropic hormone (ACTH)/adrenal cortex axis, therein elevating ACTH and cortisol secretion. The degree of this effect is both dose and compound specific, as well as being more pronounced during nighttime hours, when there are inherent diurnal rises in circulating ACTH and cortisol (Healy et al., 1983; Kettel et al., 1991; Chwalisz et al., 1992).
In the context of estrogen-induced mitogenesis, as it occurs in proliferative endometrium, antiprogestins can also be antiestrogens (Figure B11.4). However, since such antiproliferative actions do not arise through competitive binding of antiprogestins to the estrogen receptor (apparently postreceptor binding mechanisms intervene), the inhibition of tissue growth is called a noncompetitive antiestrogenic activity. This is very different from that achieved by tamoxifen or clomiphene (van Uem et al., 1989; Wolf et al., 1989b; Chwalisz et al., 1991). Moreover, this antiproliferative action of antiprogestins is not a manifestation of a progestin-like agonist activity. As revealed by the concentration of estrogen receptors in endometrial tissue, antiprogestins elevate the estrogen-receptor concentration by about sixfold (Neulen et al., 1990), yet paradoxically mitogenesis due to estrogen-induced growth is strik-