‘Placental clock’ sets human birth timing

Leigh MacMillan, Ph.D.
Published: June, 2010


Endocrinologist Roger Smith checks on a premature baby at the John Hunter Hospital in Newcastle, Australia.
Photo courtesy of Stephen McInally

It comes as no surprise to Roger Smith, M.B.B.S., Ph.D., that birth timing would be under hormonal control.

“I’m a hormone specialist,” says the director of the Mothers and Babies Research Centre Endocrine Unit at John Hunter Hospital in Newcastle, Australia. “I think everything has to do with hormones.”

Smith and his colleagues have been tailing reproductive hormones for more than two decades. In 1995, they reported in Nature Medicine that corticotropin-releasing hormone (CRH) is produced by a “placental clock” that controls the length of human pregnancy.

CRH was originally characterized as part of the body’s stress-response system. It is secreted in the brain to stimulate the release of corticotropin (ACTH) from the pituitary in the brain. That ACTH, in turn, prompts the adrenal gland to produce the “stress hormone” cortisol and other steroids.

But during pregnancy, the placenta also produces CRH and releases it into the maternal and fetal circulation.

Smith and his colleagues measured concentrations of CRH and CRH-binding protein in serial blood samples obtained from 485 pregnant women during the second and third trimesters. CRH, they found, was detectable in the maternal circulation from early in the second trimester; it rose exponentially (the concentration increased faster and faster) as pregnancy progressed; and its pattern of increase tracked with birth timing.

“If CRH goes up more rapidly than usual, then the woman is likely to deliver prematurely,” Smith explains. “If it goes up more slowly than usual, she’s likely to deliver late.”

This kind of rapid increase in CRH concentrations requires what’s called a “feed-forward system,” Smith says. CRH acts on the pituitary to prompt the release of ACTH, which stimulates cortisol production by the adrenal glands. The cortisol stimulates more CRH production by the placenta. And so on.

For births that occur at term, the investigators believe that the exponential increase is a function of normal placental growth: more placental cells make more CRH and push the feed-forward system into action. A stressor to the mother or baby – such as nutritional status, infection and social stressors – would increase production of the stress hormone cortisol and ramp up CRH production too early, resulting in premature birth.

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