An animal study at the National Institutes of Health has produced intriguing evidence that a pregnancy hormone may protect the developing fetus from the ravages of the human immunodeficiency virus, HIV. The study also points to a potential role for the hormone in fighting HIV-related wasting. The hormone in question is human chorionic gonadotropin, abbreviated hCG. Normally produced by the placenta to help maintain pregnancy, hCG is the hormone that produces a positive pregnancy test.
The possible connection between hCG and HIV was studied in a special strain of transgenic mice. The mice had been engineered to contain an incomplete set of HIV genes in the DNA of every cell in their bodies. The virus could not reproduce, but could trick certain mouse cells into making many of the viral proteins. Baby mice that inherit HIV DNA from each transgenic parent eventually accumulate enough viral protein that they develop skin lesions, wasting syndrome, and die within 3 to 6 weeks.
However, when the mice were treated with hCG, the majority of the animals showed normal weight gain as long as they were receiving the hormone. Furthermore, their cells produced considerably less viral protein than animals not receiving hormone treatment, and skin lesions were dramatically reduced. The study appears in the April 2 issue of The Journal of Clinical Investigation.
The results of this study could have implications in treating human HIV infection, according to Dr. Abner Notkins, who directed the research at the National Institute of Dental Research (NIDR). "Human chorionic gonadotropin may be another weapon to use against HIV," said Dr. Notkins. "The hormone may explain the relatively low rate of HIV transmission from mother to infant, and also could have potential for treating HIV-associated wasting syndrome in children and adults."
Dr. Notkins and his colleagues first recognized that maternal hormones might have a protective effect against HIV when they observed that newborn transgenic mice appear normal in size and weight, but soon show marked growth retardation. By 8 days of age they weigh 60 percent less that their normal littermates. It appeared to the investigators that the baby mice were protected by maternal hormones during pregnancy, and became susceptible to the effects of HIV once the level of hormones dropped dramatically at birth.
To test this theory, Dr. Swapan De, lead author on the paper, implanted tiny hormone-containing pumps under the skin of nursing mothers. As a result, the baby mice maintained an elevated level of hormones by way of the mother's milk. At weaning, the young mice continued to receive hormones by injection. In addition to intact hCG, Dr. De and his collaborators also evaluated the effects of the two separate components that make up the molecule, called the alpha and beta subunits. The alpha subunit is common to several closely related hormones, but the beta subunit gives hCG its identity and is the site of its activity. Other hormones tested were estrogen, progesterone, and dexamethasone--a potent synthetic steroid.
Only hCG and its beta subunit reduced the production of HIV proteins and protected the mice from skin lesions and wasting. If treatment was withdrawn, the symptoms appeared and the animals died. The alpha subunit was ineffective, and the other hormones not only failed to protect the mice, but actually accelerated the onset of symptoms.
Scientists still don't know the exact mechanism by which hCG inhibits HIV. However, the NIDR results support test tube studies from other laboratories, which showed that hCG or its beta subunit could lower production of the viral proteins and block cell-to-cell transmission of HIV. The beta subunit has even been shown to kill Kaposi's sarcoma cells in the laboratory and prevent these cells from producing tumors in mice.
Collaborating with Drs. De and Notkins were Mr. Charles R. Wohlenberg, Ms. Nancy J. Marinos, Mr. Davanand Doodnauth, and Dr. Joseph Bryant from the National Institute of Dental Research. NIDR is one of the National Institutes of Health located in Bethesda, Maryland.