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| Material and methods |
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| Female Wistar - Albino rats,weighing 200-250 g,were obtained from the Research Center of the University of Uluda� Bursa. The fetuses were delivered from timed pregnant mothers by cesarian section at the 15th and 17th days gestation.The rats were anesthetized with 50 mg / kg Na - pentobarbital by intraperitoneal injection. Statistical analysis was done by Student's t-test. For plasma corticosterone levels we used ICN-Biomedicals Inc RSL I 125 corticosterone KIT for rast and mice (ng/ml). For length and witdh measurement we used a compass.Weights were measured by sensitive scale. |
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| Preliminary study |
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| We performed this study in three groups with 30 rast. |
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| Group 1 (n = 10) : after anesthesia the abdomen was clened with povidine - iodine solution and shaved.We used bilateral flank incisions and excised both adrenal glands.Hemotasis was achieved with gauze tamponade.The incions were closed with 3/0 silk suture. |
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| Group 2 (n = 10) : the rast were submited to a sham procedure by a median laparotomy. |
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| Group 3 (n = 10) : this was a control group. |
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| The rast in all groups were cannulized via a. carotis communis. |
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| While the rats in Group 1 died postperatively within 8 hours the rats from Group 3 survived.Only one rat from group 2 died. |
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| Analysis of the corticosterone levels among the 3 groups showed no significant difference. |
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| Grafting method |
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| The fetuses were delivered from timed pregnant mothers by cesarian section.They underwent cercival disconnection and the fetal adrenal glands were excised quickly and placed in 4*C normal salina solution.Cold ischemic time was 30 minutes. |
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| Staged bilateral adrenalectomy |
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| We constructed a 4th group (Tx group) with 20 rats and performed left flank incision approximately 2 cm long and retracted the left kidney medially.With this manoeuvre we achieved a good exposure of the left adrenal gland and excised it.After hemostasis we took the great omentum out of the wound and placed the whole fetal adrenal glands into the omentum.A 6/0 prolene suture was placed as a marker.The incision was closed with 3/0 silk.(Stage 1). |
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| All 20 rast survived this stage and 6 weeks later we performed on the same rats right adrenalectomy (stage 2). |
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| During this procedure all rast were cannulized via a.carotis communis. |
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| Graft removal |
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| After the second stage when the rats died , the abdomen was opened and the grafts were found in the omentum and excised (Fig.1). 6 surviving rats were sacrificed on the 16th day for histopathologic examination. |
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| Results |
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| Mophological findings |
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| The mean weights of the fetal adrenal grafst increased from 2.67 g to 40.6 g (Fig.2).The mean lengths and widths of the grafts showed a significant increase (Fig.3).Histologic examination of the grafts under light micoscopy revealed 3 zones of the adrenal cortex but we could not find any medullary cell (Fig.4). |
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| Physiological findings |
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| The analysis of the corticosterone levels among the 4 groups showed no significant difference (Fig.5). |
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| The comparison of the survival of the rats from Group 1 (bilateral adrenal ectomy) with Group 4 (Tx group) was considerable. |
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| In Group 1 all the rats died after bilateral adrenalectomy within 8 hours.But in Group 4 totally adrenalectomized rats with fetal adrenal grafts did not die within 8 hours.One rat died at 10th hour,five rats at 2nd day,six rats at 3rd day,one rat 4th day,one rat at 6th day and six rats survived (Fig.6). |
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| Discussion |
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| Bilateral adrenalectomy for Cushing's syndrome has been the mainstay of treatment since 1945 (5).Because of the subsequent complications of bilateral adrenalectomy and permanent dependence on steroid replacement,many authors performed autotransplantation after bilateral adrenalectomy (5,6.8,11).But results of human adrenal autotransplantion have been difficult to evaluate and success has been infreguent.On the other hand autotransplantation has no place in neoplastic disease of either cortex or medulla. |
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| Our guestion is : Can fetal adrenal gland transplantation be beneficial in these cases ? |
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| The aim of the present study is to evaluate the usefulness of fetal adrenal transplants in adrenalectomized rats. |
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| We know from published reports that many ex perimental studies showed successful transplantation of fetal adrenal glands into adult rats (1,3,9). |
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| Studies of Foglia and Trammer showed,that the fetal adrenal grafts had significantly grown compared with their original size (3,9).These results were similar to our findings.Histological investigation of previous studies have shown the vanishing of medulla after whole adrenal transplantation due to the failure to neovascularize the gland center (2,4,7,10). Since we could not find at examination any medullary cell,we would agree with this finding consideration. Neverthelees it requires further investigation. |
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| In addition to these morphological findings we investigated the corticosterone levels.Our results showed no significant difference between the adrenalectomized rats of Group 1 and the rats of Tx group. |
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| Andrew pointed out in this study that adrenalectomized rats showed lower corticostereone levels than the rats who underwent autotransplantation after bilateral adrenalectomy (1). Also,in contrast with his study,we found in our preliminary study early deaths of the rats after bilateral adrenalectomy within 8 hours. |
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| In conclusion,we speculate from our findings that fetal adrenal grafts functioned in staged adrenalectomized rats. |
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| References |
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�Andrew W,Connors M : Autotransplantation of adrenal cortical tissue : A rodent model.Surgery 98 (1985) 995-999
Brenner RM,Patt DI,Wyman LC : Cellular changes during adrenocortical regenaration in the rat.Anat Rec 117 (1953) 795-771
Foglia RP,Ouaglia ML,Preta JD,Donahoe PK : Can fetal and newborn allografts survive in an immunocompetent Host ? J Pediatr Surg 21 (1986) 608-612
Greep RP,Deane HW : Histological,cytochemical and physiological ob servations on the regeneration of the rat's adrenal gland following enucleation.Endocrinology 45 (1949)42-56
Hardy JD : Autotransplantation of adrenal remmant to thigh in Cushing's disease:JAMA 185 (1963)134
Ibbertson HK,O'Brien KP : Adrenal outografts in treament of Cushing's disease.Brit Med J 2 (1962) 703
Ingle DJ,Higgins GM : Autotransplantation and regeneration of the adrenal gland.Endocrinology 22 (1938) 458-464
Nelson DH,Sprunt JG,Mins MRB : Plasma ACTH defermination in 58 patients before or after adrenalectomy for Cushing's syndrome.J Clin Endocrinol 26 (1966) 722
Trammer A,Kellnar ST,Wilsch U : Transplantation of fetal adrenal glands in rats.Presented in Congress of the 5th Pediatric Research Berlin (1991)
William CE : Adrenal transplantation and pituitary adrenal funtion.Am J Physiol 250 (1986) 87-93
Zieleniewski J,Stapar K : Late results af bilateral adrenalectomy and implantation af a part of the adrenal cortex in Cushing's syndrome.Polish Endocrinol 23 (1972) 324
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