PROLACTIN LOWERING ACTIVITY OF THE RETINOID RO-14-9706 AFFECTING LACTATION AND PUP SURVIVAL

The arotinoid Ro 14-9706, though devoid of any teratogenic potential, was found to reduce dose dependently the survival of pups when their m others were treated with toxic doses during days 6-15 of gestation. Th e increased mortality was primarily seen during early lactation. When pups derived from treated mothers were nursed by control foster mother s unexposed to the drug, their survival was significantly improved ind icating that the increased mortality was not solely due to fetal drug exposure. When pups derived from untreated mothers were fostered by da rns that were exposed to the arotinoid during pregnancy, a significant pup mortality (p < 0.01) was observed, suggesting that the nursing be haviour of lactating darns was seriously affected. This impairment cou ld be linked to a prolactin-suppressive activity of the arotinoid duri ng lactation which was also seen during pregnancy. Other pituitary hor mones, however, were not affected by the compound. Although the drug i nduced pronounced structural alterations in mitochondria of adrenocort ical cells, visualized by light microscopy as extended vacuolization i n the zona fasciculata and reticularis, this pathological finding did not translate into functional impairment of steroidogenesis. Thus, the arotinoid Ro 14-9706 exhibits in rats a prolactin-suppressive activit y which affects lactation and subsequently pup survival. This particul ar endocrinological interference is a new phenomenon and uncommon for retinoids.