Proliferation, zonal maturation, and steroid production of fetal adrenal transplants in adrenalectomized rats

The present study investigated the histologic maturation, proliferative cap acity, and steroid production of fetal adrenal transplants (Tx) in adrenale ctomized rats. A pair of fetal adrenal glands (18-20 days of gestation) was transplanted into the omentum of syngeneic Lewis rats (n = 45). Four weeks later, in 5 animals the grafts were excised for morphologic evaluation. Pr oliferation was investigated by immunohistochemical staining for KI-67 prot ein and quantified by the proliferation index (PI = positive cells/100 coun ts). All other hosts (Tx; n = 40) underwent bilateral adrenalectomy (AE) to induce Addisonian crisis. Postoperatively, survival and concentrations of potassium, sodium, aldosterone, and corticosterone were recorded for 6 mont hs. These data were compared to controls (C-only AE; n = 30) and a sham gro up (S; n = 10). At the end of the study period all surviving hosts were kil led for histologic examination of grafts. At 4 weeks post-Tx the adrenal gr afts demonstrated a distinct zona glomerulosa and frequent proliferation wi th a PI of 0.084, comparable to normal control (0.092). Following AE surviv al was significantly prolonged in Tx (86% vs 12% of C, P < 0.05). Control a nimals developed severe hyponatremia and hyperkalemia, whereas in Tx only t ransient signs of Addisonian crisis were recorded. Levels of aldosterone dr opped within 7 days in the Tx and C groups, but returned to normal for Tx w ithin 8 weeks. Corticosterone levels of Tx animals fell to 25% within week, but steadily increased to 70% by the end of the study. At 6 months, grafts revealed a mature adrenocortical structure with little proliferative activ ity, which was comparable to controls. In a syngeneic rat model fetal adren al transplants thus mature and proliferate to provide sufficient steroid pr oduction for adrenalectomized hosts.