C21 STEROID METABOLISM AND CONJUGATION IN THE HUMAN PREMATURE NEONATE

Abstract

ABSTRACT The metabolism and conjugation in vitro of exogenous cortisol, 11-deoxycortisol, corticosterone and pregnenolone by liver, adrenal, kidney, intestine, lung, thymus, spleen and skin tissue preparations of premature and full-term newborn infants were studied. A number of tissues possess the enzymatic capacity to transform cortisol to its major metabolites, while metabolism of 11-deoxycortisol was effected exclusively by adrenal tissue preparations. 6β-Hydroxylation of exogenous cortisol was demonstrated by liver, adrenal and intestinal tissue, the latter being the most active. In the liver, 6β-hydroxylation of cortisol was associated with the "mitochondrial" sediment. The conversion of cortisol to cortisone was effected by all tissue preparations, except perhaps the lung in which it was not characterized, but was most pronounced when kidney or adrenal preparations were used as the source of enzymes. Ring A reduction of cortisol to tetrahydro-metabolites was demonstrated by all tissue preparations with the exception of the thymus. Similarly, all tissue preparations were able to produce glucuronide and sulphate conjugates of cortisol metabolites, though the formation of steroid sulphates was relatively low in all tissues under the present experimental conditions. Glucuro- and sulpho-conjugation was effected more readily when pregnenolone and corticosterone were used as substrate instead of cortisol. It is concluded that conjugation and catabolism of corticosteroids, namely cortisol, corticosterone and pregnenolone in the neonate may be the function of many tissues coordinated by factor(s) presently unknown.