In a finding that could lead to breakthroughs in the treatment of premature infants with immature skin, UCSF scientists have identified hormone activators that stimulate skin development in premature rats.

"This may be an important finding for premature infants, who often lack a competent skin barrier," said Mary Williams, UCSF adjunct professor of dermatology and pediatrics. "An immature skin barrier can contribute to the illness and death of these premature infants."

Williams and her UCSF research colleagues presented their findings on fetal skin development today (May 4) at the 1998 Pediatric Academic Societies' annual meeting.

Mammals normally have a competent skin barrier -- skin that can prevent excessive water loss from the inside of the body to the outside air -- at birth. This barrier is formed by the outermost layers of the skin, the multilayered stratum corneum (SC), which consists of dead cells surrounded by sheets of fat. The SC is made by the epidermis, a layer of skin just beneath the SC that is made up of living cells.

But babies born under 32 weeks of gestation lack this barrier and have been shown to have a very thin SC, said Williams. "Without this barrier these infants are susceptible to hypothermia, water loss, electrolyte imbalance, and infection," she said.

Previous studies on fetal rat skin cells by UCSF researchers have shown that formation of a competent barrier is accompanied by formation of a multilayered SC. Certain hormones, such as thyroid hormone and estrogens have also been shown to accelerate barrier maturation. However, past research has shown these hormones are not required for barrier formation.

Williams and research colleagues have previously shown that certain activators, molecules that bind to the surface or receptors of hormones, accelerate barrier formation. Some activators for hormone receptors, PPAR alpha and FXR, are generated in the skin itself, suggesting the process of skin development may be regulated internally.

Given these findings, UCSF researchers studied whether activators of PPAR alpha and FXR accelerated the maturation of the SC and the epidermal barrier in fetal rats during normal gestation.

Rats, who have a normal gestation of 22 days, were injected with activators through the amniotic fluid at 17 days. Control groups received placebo injections which lacked activators. Premature rats were then delivered on day 19. Researchers measured both structure and function of the skin barrier in the premature rats.

"Activators accelerated the development of the competent skin barrier" according to Williams. "Rats injected with PPAR alpha or FXR activators exhibited less water loss than the control groups."

Researchers found that fetal rats who received the activators developed a competent barrier by 19 days. Normally a skin barrier does not develop in rats until 21 days. A distinct SC was present in treated rats while those in the control groups lacked a well-defined SC. The activity of two enzymes involved in the formation of the SC were also increased in fetal rats with activators.

Finally, proteins associated with a mature SC and a competent barrier were present in the rats injected with the activators, but not in the control groups.

The co-investigator on the study is Kenneth Feingold, UCSF professor of medicine and dermatology.

by Lordelyn P. del Rosario

1st appeared 5/4/98

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