RETINOIC ACID AND ALCOHOL RETINOL DEHYDROGENASE IN THE MOUSE ADRENAL-GLAND - A POTENTIAL ENDOCRINE SOURCE OF RETINOIC ACID DURING DEVELOPMENT/

Retinoid signaling requires the conversion of retinol to retinoic acid by a two-step process, the first of which can be catalyzed in vitro b y class I and class IV alcohol dehydrogenases (ADH). These enzymes may participate in local retinoic acid synthesis in some target tissues, although other studies suggest retinoic acid may also be supplied to t issues via the bloodstream, much like an endocrine hormone. Here we ha ve analyzed the expression of these two ADHs as well as retinoic acid production in the adrenal gland, an organ known to be an endocrine sou rce of other hormones. In situ hybridization revealed high levels of b oth class I and class IV ADH messenger RNAs in adrenal glands of 16.5- day mouse embryos and adults. Class I ADH protein was immunohistochemi cally detected in embryonic and adult adrenal glands, the latter prima rily in the zona fasiculata of the cortex. Abundant class IV ADH prote in was detected in the embryonic adrenal as well as in the zona glomer ulosa and zona fasiculata of the adult adrenal cortex. Interestingly, class IV ADH protein was found in only a subset of adult cortical cell s arranged in radial columns, thus providing further evidence for cent ripetal cell migration during adrenocortical differentiation. Using a retinoic acid bioassay, adrenal glands from 16.5 day embryos were foun d to have significantly higher levels of retinoic acid than embryonic liver. The adult adrenal was found to have approximately 15.5 pmol/g o f retinoic acid, whereas the adult liver had 24.8 pmol/g, and brain, h eart, and spleen each had less than 1.0 pmol/g. Because previous findi ngs indicate that the adrenal gland is not a retinoid target tissue, o ur detection of both alcohol/retinol dehydrogenases and significant am ounts of retinoic acid in this organ suggests that it functions as a p otential endocrine source of this hormone during mouse development.