Previous studies of sucrase-isomaltase (SI) activities have shown this complex to be absent in the suckling rat and to appear during the weaning period. We describe here the cloning of a heterologous SI cDNA and its use for the quantitation of SI mRNA as a first step toward understanding the molecular basis of SI development. A survey of RNA from 12 tissues of mature rats by Northern blot analysis showed a 6-kb band of SI mRNA only in the small intestine. Within the latter, both sucrase activity and SI mRNA peaked in the jejunum. Assay of jejunal tissue from developing rats showed sucrase activity and SI mRNA to be first detectable at 18 days, to rise in parallel through 24 days, and then to diverge a little (enzyme activity being lower) by 36 days. When glucocorticoid was administered to 10-day-old rats, neither sucrase activity nor SI mRNA was detectable 12 h later. Both parameters were readily detected 24 h postinjection, although the mRNA had risen relatively more than the enzyme activity. The two parameters increased in concert through 5 days postinjection and then plateaued. We conclude that, with respect to distribution along the intestine and to normal and precocious development, activities of SI in the rat are determined primarily by the abundance of its mRNA.

Jejunal sucrase is known to display glucocorticoid responsiveness from birth through day 17 but not beyond that age. The aim of the current study was to determine whether this abrupt loss of responsiveness was shared by maltase, lactase, and acid beta-galactosidase. Glucocorticoid concentrations were manipulated by both adrenalectomy (ADX) and by administration of cortisone acetate (CA). Surgery or treatment was performed on each day from 16--22 days of age. Maltase activity was reduced by ADX at day 18 and earlier and was increased by CA at days 16 and 17. There were no effects at later ages. Acid beta-galactosidase was increased by ADX only at day 18 and earlier and was decreased by CA only at day 16. Lactase activity was increased by ADX at all ages up to and including day 20 but was reduced by CA only at days 16 and 17. Thus, we conclude that loss of glucocorticoid responsiveness at a relatively early stage of development is a common feature of both brush-border and lysosomal enzymes of the small intestine.

ABSTRACT. Infant rats exhibit a marked rise in serum concentrations of corticosterone between postnatal days 12 and 24. As this rise appears to be cued by L-thyroxine, the aim of the current study was to determine the physiological bases of the effects of both age and thyroid status on serum corticosterone. The in vivo response to either adrenocorticotropic hormone (60 mU/g body weight) or dibutyryl 3',5'-cyclic adenylate (0.3 mg/g body weight) increased between 10 and 16 days and was advanced and delayed by hyper-and hypothyroidism, respectively. In contrast, in vitro studies with adrenals from rats aged 10 and 16 days showed no effect of age on either basal or adrenocorticotropic hormone-stimulated production of corticosterone. Chronic administration of exogenous corticosterone to hyperthyroid animals resulted in significantly higher concentrations of serum corticosterone than did an identical administration to hypothyroid animals. In the neonatal rat, circulating concentrations of corticosterone are extremely low on days 6 through 12, then they rise markedly beginning on day 14 and reaching a peak on days 24-25 (1-3). During this same period the circulating concentrations of ACTH do not change significantly (4). Thus, either the ontogenic increase of corticosterone is independent of ACTH or the system becomes increasingly responsive to the basal concentration of ACTH. There is conflicting evidence regarding the latter possibility (4-6) and the data are difficult to interpret because of the use of a fluorometric method for measuring corticosterone which is now recognized to be inappropriate in young rodents (1, 2, 7).

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ABSTRACT. Corticosterone plays an important role in the regulation of postnatal development in the rat. Basal concentrations of plasma corticosterone increase markedly during the 3rd wk of life. To date, however, the physiologic bases of this increase have remained unclear. To understand the determinants of circulating concentrations of corticosterone during this period, the plasma half-life of disappearance at steady state (tlh), the apparent volume of distribution, and metabolic clearance rate were determined after injection of a tracer dose of 3H-corticosterone in rats at 12, 16, and 22 days of age. The tlh for total plasma corticosterone decreased with increasing age. The volume of distribution decreased even more steeply and, consequently, the MCR displayed a highly significant decline between 12 and 22 days of age. As plasma concentrations of corticosteroid-binding globulin are known to increase markedly during this period, the t~ of protein-bound corticosterone was measured and that of free corticosterone was computed. At all ages the tth of bound corticosterone was less than that of free corticosterone. Protein binding of the injected 3H-corticosterone increased significantly with development. Thus, increased binding of corticosterone is associated with decreased t~. The increasing association of corticosterone with corticosteroid-binding globulin during this developmental period is the most likely explanation for the steep decline of volume of distribution and thus of the metabolic clearance rate for corticosterone. The latter provides, for the first time, an understanding of the basis of the developmental increase in plasma concentrations of corticosterone. (Pediatr Res 24: 595-599,1988)