Pregnancy Hormone Repairs MS-type Neural Damage

CALGARY, Alberta, Feb. 21 -- A pregnancy hormone may offer a key to halting or reversing the progression of multiple sclerosis and other demyelinating diseases, researchers here reported.

Prolactin, the hormone that stimulates lactation during pregnancy, also appears to stimulate spontaneous production of myelin, which may explain why MS usually goes into remission during pregnancy, reported Samuel Weiss, Ph.D., the University of Calgary, and colleagues in the Feb. 21 issue of the Journal of Neuroscience.

"It is thought that during pregnancy, women's immune systems no longer destroyed the myelin," said Dr. Weiss. "However, no previous study has tested whether pregnancy actually results in the production of new myelin, which may lead to improvement of symptoms."

The authors discovered the remyelinating effects of prolactin in pregnant mice, and confirmed their finding by injecting the hormone into non-pregnant female mouse models for MS. The hormone simulated the effects of elevated prolactin levels in pregnancy, resulting in new myelin production and repair.

"Agents promoting remyelination will be beneficial not only for typical demyelinating diseases like MS, but also for many other neurological disorders, such as spinal cord injuries and stroke," commented Fred H. Gage, Ph.D., of the Salk Institute for Biological Studies in La Jolla, California. Dr. Gage was not involved in this study.

The investigators have identified the first known example of an innate biological mechanism for generating myelin in the adult central nervous system, they said.

Prolactin is produced in the anterior pituitary by oligodendrocytes, and is present at varying levels in both men and women. During pregnancy, the hormone is synthesized and released at levels 10- to 20-fold higher than normal.

"Multiple sclerosis, a demyelinating disease more common to females than males, undergoes remission during pregnancy, and this is correlated with a decrease in the number and size of active white matter lesions," the investigators wrote. "Thus, we hypothesized that pregnancy promotes increases in oligodendrocyte precursor cell proliferation, which bestows an enhanced capacity to generate oligodendrocytes and regenerate myelin in the maternal CNS."

To test their hypothesis, they determined that increased oligodendrocyte and precursor cell proliferation occurs during pregnancy in mice, and then looked for evidence of a change in the number of myelinated axons in the maternal central nervous system during the postpartum period.

"Remarkably, we observed a 50% increase in the number of myelinated axons in the genu of the corpus callosum in postpartum-day 14 females relative to age-matched 11-week-old virgins," they wrote.

The investigators then confirmed that remyelination was occurring in the postpartum CNS by comparing virgin and pregnant mice that had been injected with a detergent (lysolecithin) that creates MS-like lesions that normally begin to spontaneously remyelinate in about seven days. The pregnant mice had an 80% increase over the virgin controls in the number of labeled oligodendrocytes in the lesioned portions of the brain.

In the final steps of their experiment, they determined that prolactin signaling regulates pregnancy-induced proliferation of oligodendrocyte precursor cells, and then demonstrated that treatment with prolactin could enhance white matter regeneration in virgin female mice. They saw a 74% increase in labeled oligodendrocytes in the lesions of animals that had received intraperitoneal injections of prolactin, compared with controls.

"Prolactin signaling is necessary and sufficient for the pregnancy-induced increase in oligodendrocyte proliferation, and prolactin treatments mimic the regenerative effects of pregnancy on myelin damage in virgin females," the authors wrote. "These results identify a novel form of white matter plasticity in the adult CNS and suggest that prolactin may have therapeutic potential for the treatment of white matter damage."

"This discovery has the potential to take MS therapy a step further than current treatments that stabilize the disease in its early stages," said Luanne Metz, MD, director of the Calgary MS Clinic at the University of Calgary and Calgary Health Region, who was not involved in the study. By promoting repair, which is the goal of prolactin therapy, we have hope of actually improving symptoms in people with MS."