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

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Abstract
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, hydro-cortisone and aldosterone) differentiate into lobuloalveolar structures. These differentiation processes were inhibited by retinoic acid at 106 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 lobulo-alveolar 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.