The effects of cortisol and BUDR on cellular differentiation in the small intestine in suckling rats

In suckling rats absorptive cells in the distal two‐thirds of the small intestine ingest colloids by pinocytosis. In the middle third of the intestine pinocytosis ceases 17 to 21 days after birth and can be halted prematurely by glucocorticoids. The adrenal cortex is relatively inactive in newborn rats and begins to secrete glucocorticoids two weeks after birth; this secretion has been suspected to cause the termination of pinocytosis. Glucocorticoids do not stop pinocytosis in absorptive cells already present on the villi but induce the renewing population of cells in the crypts to replace the cells on the villi with new ones that do not engage in pinocytosis. Therefore, glucocorticoids act by inducing a new direction of cellular differentiation. BUDR (5‐bromodeoxyuridine) is reported to inhibit cellular differentiation reversibly in vitro . When injected into 8 to 9‐day‐old rats, simultaneously with cortisol, it inhibited the change in cellular differentiation induced by cortisol; that is, pinocytosis continued unabated. BUDR did not appear to be toxic and did not interfere with cellular replacement in the small intestine, as judged autoradio‐graphically. Thus it appears that BUDR inhibits the initiation of cellular differentiation by cortisol but does not interfere with cellular proliferation or the pre‐established program of cellular differentiation that leads to pinocytosis. The mechanism of action of BUDR is still unknown; it is discussed in light of the possibility that BUDR may after cellular differentiation without acting directly on the genome.