Mammal birth signal cues tadpole to morph

Researchers have long known that hormones from the thyroid play a big role in amphibian metamorphosis. In a 1912 experiment, tadpoles began to change form when they were fed thyroid glands from horses.

 Denver manipulated the tadpoles with a hormone produced by a part of the brain called the hypothalamus. When he injected a synthetic version of corticotropin-releasing hormone (CRH) into the tadpoles, their thyroid hormones increased and metamorphosis proceeded faster than normal. When he injected molecules known to block the activity of CRH, metamorphosis was slowed.

 More evidence of CRH's control came from altering water levels in the tadpoles' aquariums. As the water was gradually decreased, the tadpoles increased their CRH production and went through metamorphosis within 26 days of hatching. Tadpoles kept in high water remained immature after 36 days.

 In all vertebrates, CRH "is exquisitely sensitive to stress in the environment," says Denver. When the brain registers trouble, whether in a shrinking pond or on a rush-hour freeway, it churns out the hormone. CRH exerts its influence by acting on the pituitary, which then produces hormones that fire up the thyroid and renal glands. These two glands produce additional hormones that help an organism cope with the stress -- in the toad's case, by turning on the growth of limbs, including the spadelike spurs on its feet that enable it to burrow underground.

 As other researchers have shown, CRH also comes into play in mammalian pregnancy. The hormone rises just before the start of labor and delivery; in preterm births, it rises even more.

"Like the tadpole," says Denver, "the fetus produces CRH when things are becoming unfavorable. It's time then to make the transition into the next stage of the life history."

 Peter W. Nathanielsz of Cornell University's Laboratory for Pregnancy and Newborn Research says Denver's analysis "makes very good sense. . . . Here is a very old system of metamorphosis in tadpoles which utilizes CRH, and that same system has been put to use in labor and delivery."

 Salmon also seem to use the CRH signal to move into the adult stage, Denver adds. Other vertebrates must be studied to find out whether CRH has always been evolution's way of saying "move on."