A hormone's reputation takes a beating - knock-out mice lacking gene for oxytocin mate, give birth and nurture their young naturally - Brief Article

Science News, Oct 19, 1996 by John Travis

On the behavioral front, animal studies have indicated that oxytocin drives the chemistry of mating, triggering the arching of females' bodies in readi- ness for copulation and the erections and ejaculations of males. Research on prairie voles and rats also offered a persuasive case that the hormone inspires maternal behaviors, such as nest building and licking of newborns.

Much of the conventional wisdom about oxytocin now lies in ruins. Mice deprived of the hormone mate naturally, and the females give birth on time and without apparent problems. The mothers also seem to care for their young as normal mothers do.

"This was one of those papers you hope never to have to write," jokes Thomas R. Insel, head of a research group at Emory University in Atlanta that for years has studied oxytocin's influence on mammalian behavior.

Insel and his colleagues, in collaboration with a group headed by Martin M. Matzuk of the Baylor College of Medicine in Houston, form one of three research teams that have recently created so-called knockout mice, which lack a working gene for oxytocin. The Houston-Atlanta team describes its animals in the Oct. 15 Proceedings of the National Academy of Sciences.

"There's no question the females are fully maternal," says Insel. "It's also startling to find out that mice that have no oxytocin whatsoever seem to have pretty normal reproductive behavior. I found it very difficult to accept at first." The knockout mice aren't completely normal. Confirming the hormone's role in lactation, mothers deprived of oxytocin can't nurse their young. Mouse pups die within a day unless researchers inject the mothers with oxytocin.

"The milk is there. They just don't let it down in response to suckling," says W. Scott Young III of the National Institute of Mental Health in Bethesda, Md.

Young and his colleagues will describe their oxytocin-knockout mice in the November Journal of Neuroendocrinology.

In retrospect, some researchers say, it shouldn't be surprising that oxytocin-deficient mice can still mate and bear young.

"Reproduction is just too important to have one mechanism for ensuring parturition [giving birth]. There's bound to be redundancy in the system," says Louis J. Muglia of the Washington University School of Medicine in St.

Louis. Muglia and Christina E. Luedke of Children's Hospital in Boston head the third group that has recently produced oxytocin-knockout mice.

Determining whether other hormones step in to compensate for the missing oxytocin is high on the investigators' agenda. Oxytocin, secreted by the pituitary gland into the bloodstream, triggers responses within animals by binding to cell surface proteins called receptors. The hormone vasopressin, several studies have suggested, can latch onto the same receptor that oxytocin uses.

Researchers are now racing to create mice lacking the oxytocin receptor. "If you knock out the receptor [and see no changes in behavior], that would really put the nail in the coffin of a behavioral role for oxytocin," says Harold Gainer of the National Institute of Neurological Disorders and Stroke in Bethesda.

More recent tests on the knockout mice have uncovered subtle behavioral changes. "There are clear differences in behavior, mostly centering around aggression and social investigation," says Insel. "It appears the knockout mice don't investigate other mice as much." What about oxytocin's role in people? Women who have trouble nursing their babies may have a deficiency of the hormone, speculates Insel.