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 mothers were treated with toxic doses during days 6-15 of gestation. The increased mortality was primarily seen during early lactation. When pups derived from treated mothers were nursed by control foster mothers unexposed to the drug, their survival was significantly improved indicating that the increased mortality was not solely due to fetal drug exposure. When pups derived from untreated mothers were fostered by dams that were exposed to the arotinoid during pregnancy, a significant pup mortality (p < 0.01) was observed, suggesting that the nursing behaviour of lactating dams was seriously affected. This impairment could be linked to a prolactin-suppressive activity of the arotinoid during lactation which was also seen during pregnancy. Other pituitary hormones, however, were not affected by the compound. Although the drug induced pronounced structural alterations in mitochondria of adrenocortical cells, visualized by light microscopy as extended vacuolization in 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 activity which affects lactation and subsequently pup survival. This particular endocrinological interference is a new phenomenon and uncommon for retinoids.
Edelmann
A
A
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Galli
B
B
Hennes
U
U
Kistler
A
A
Kuhn
H
H
Mettler
F
F
D000302:Adrenal Cortex / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D003879:Dermatologic Agents / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D006728:Hormones / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects; D007774:Lactation / Q000187:drug effects*; D009026:Mortality; D009281:Naphthalenes / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011388:Prolactin / Q000187:drug effects*; D051381:Rats; D013450:Sulfones / Q000633:toxicity*
D003879:Dermatologic Agents; D006728:Hormones; D009281:Naphthalenes; D018377:Neurotransmitter Agents; D013450:Sulfones; C069613:sumarotene; D011388:Prolactin