EPIDERMAL STEROID SULFATASE AND CHOLESTEROL SULFOTRANSFERASE ARE REGULATED DURING LATE-GESTATION IN THE FETAL-RAT

Lipids in the stratum corneum (SC) are organized into lamellar membran e unit structures that provide the permeability barrier, Cholesterol s ulfate, a SC membrane lipid, is synthesized by cholesterol sulfotransf erase (CSTase) in the lower epidermis and hydrolyzed to cholesterol by steroid sulfatase (SSase) in the SC, To determine whether these enzym es are induced during barrier ontogenesis, we examined their activity in epidermis of fetal rats before (gestational day 17), during (day 19 ), and after (day 21) barrier formation, CSTase activity increased sim ilar to 10-fold between day 17 and day 19, then declined between day 1 9 and day 21. In contrast, SSase activity reached its peak activity on day 21, increasing >5-fold, Fetal rat skin explants develop a SC and barrier over the same time course in vitro as in utero, Likewise, CSTa se and SSase activities during in vitro ontogenesis precisely mirrored those obtained in utero, Moreover, hormones that accelerate barrier o ntogenesis (e.g. glucocorticoids, thyroid hormone, and estrogen) accel erated the increase in CSTase and SSase activities during in vitro ont ogenesis; mRNA levels of SSase increased in parallel with enzymatic ac tivity, suggesting that these developmental changes are regulated at t he genomic level, Finally, addition of exogenous cholesterol sulfate t o explants in vitro did not accelerate either SC development or barrie r formation, These studies suggest that induction of the cholesterol s ulfate cycle enzymes during SC ontogenesis is a component of the fetal epidermal differentiation program and that the synthetic and degradat ive enzymes of this pathway are differentially regulated.