In the developing rat kidney, there is no separation of the medulla into an
outer and inner zone. At the time of birth, ascending limbs with immature
distal tubule epithelium are present throughout the renal medulla, all loop
s of Henle resemble the short loop of adult animals, and there are no ascen
ding thin limbs. It was demonstrated previously that immature thick ascendi
ng limbs in the renal papilla are transformed into ascending thin limbs by
apoptotic deletion of cells and transformation of the remaining cells into
a thin squamous epithelium. However, it is not known whether this is the on
ly source of ascending thin limb cells or whether cell proliferation occurs
in the segment undergoing transformation. This study was designed to addre
ss these questions and to identify sites of cell proliferation in the loop
of Henle. Rat pups, 1, 3, 5, 7, and 14 d old, received a single injection o
f 5-bromo-2'-deoxyuridine (BrdU) 18 h before preservation of kidneys for im
munohistochemistry. Thick ascending and descending limbs were identified by
labeling with antibodies against the serotonin receptor, 5-HT1A, and aquap
orin-1. respectively. Proliferating cells were identified with an antibody
against BrdU. BrdU-positive cells in descending and ascending limbs of the
loop of Henle were counted and expressed as percentages of the total number
of aquaporin-1 -positive and 5-HT1A-positive cells in the different segmen
ts. In the developing kidney, numerous BrdU-positive nuclei were observed i
n the nephrogenic zone. Outside of this location, BrdU-positive tubule cell
s were most prevalent in medullary rays in the inner cortex and in the oute
r medulla. BrdU-labeled cells were rare in the papillary portion of the loo
p of Henle and were not observed in the lower half of the papilla after 3 d
of age. BrdU-labeled nuclei were not observed in segments undergoing trans
formation or in newly formed ascending thin limb epithelium. It was conclud
ed that the growth zone for the loop elf Henle is located around the cortic
omedullary junction, and the ascending thin limb is mainly, if not exclusiv
ely, derived from cells of the thick ascending limb.