Structure-activity relationship of retinoids on lobuloalveolar differentiation of cultured mouse mammary glands

The influence of 28 retinoids on the structural differentiation of mouse mammary glands in whole organ cultures was examined. Mammary glands from BALB/c mice pretreated with steroids (estradiol and progesterone) and cultured in the presence of lactogenic hormones (insulin, prolactin, hydrocortisone and aldosterone) differentiate into lobuloalveolar structures. These differentiation processes were inhibited by retinoic acid at 10(-6) M and by the arotinoid containing tetramethylated tetraline (Ro 13-7410) at 10(-10) M. The presence of this arotinoid for as little as 5 min, followed by incubation in control medium, irreversibly suppressed lobuloalveolar differentiation. After pre-incubation of mammary glands in control medium for 3 days, the arotinoids no longer suppressed the differentiation of lobuloalveolar structures. Structure-activity relationships of selected retinoids with marked differences in their biological activity were similar to those reported. The mouse mammary gland in whole organ culture may be a suitable and useful bioassay system for selecting retinoids which affect differentiation processes and may thus be helpful in the treatment of oncological diseases.