The Effect of Diethylstilbestrol on the Susceptibility of Rats to Hematogenous Pyelonephritis*

Abstract

Renal infection rarely occurs after the intravenous injection of gram-negative bacteria, namely, Escherichia coli into normal animals (1). If the kidney is subjected to experimental trauma (2), ureteral ligation (3), medullary scarring secondary to cautery injury (4), or chemical injury (1), an increased susceptibility to infection results.These experimental models, however, do not expflain tile hlighl lneilence cf pyeloneptihrits in human pregnancy (5-12). The development of pyelonephritis in pregnant women has been ascribed to the anatomical and functional changes of the urinary tract usually observed from the third month of pregnancy to a few weeks after delivery (5,7,12). Dilatation of the ureters and renal pelves has been attributed to obstruction of the ureter by the pregnant uterus (13) Diethylstilbestrol.2 Pellets contained 75% diethylstilbestrol and 25% cholesterol by weight. The pellets were weighed3 and placed subcutaneously through a skin incision, 15 mm long, at the base of the neck of rats under light ether anesthesia. The incision was closed with a skin clip. At the time of sacrifice, the pellets were recovered from most animals, dried, and weighed. The amount of diethylstilbestrol absorbed was estimated to be 0.75 times the difference in pellet weight. Shamape.rAtion wart carried otA inr contrcd rktw Bacteria. The strain of F. rali (1FN 9) irud ha-a been maintained in this laboratory for 7 years, and details of its handling were described previously (3). A volume of 0.5 ml of a 4-hour culture (containing 2.5 to 7.5 X 10' organisms per ml) was injected into the tail vein of each rat. Tenfold dilutions in 0.85% sodium chloride solution were incubated in agar pour plates to enumerate each inoculum. Removal of the urinary tract for bacteriological and pathological studies. Sterile technique was maintained during all surgical procedures. Under pentobarbital anesthesia, the abdominal wall was cleaned with 70% alcohol and incised so that the entire urinary tract was exposed. After urine and blood were collected in some ahiiiiiil, tsia kidneys, ufeters, and bladletbr weic iviliuved and placed in Petri dishes for macroscopic examination and sectioning. A mid-line longitudinal section was made in each kidney which appeared grossly abscessed or hydronephrotic. One-half of the kidney, both ureters, and the bladder were fixed in 10%o formol for histological examination. The remaining half of the kidney was placed in a Teflon tissue homogenizer and ground in 4.5 ml of 0.85%o sodium chloride solution until a homogeneous suspension was obtained. Whole kidneys were cultured after homogenization with 9.0 ml of saline. These concentrations represented a 101 dilution. Subsequent tenfold dilutions were prepared in saline solution. Agar pour plates were made from these dilutions, and colony counts were determined after incubation for 48 hours.Counts ranging between 30 and 300 colonies were taken as most nearly representative. When the greatest dilution contained too many colonies to be counted, the numDiethylstilbestr...

Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

“…In some animals, the hydronephropathy was complicated by acute pyelonephritis, whereas others appeared to have chronic interstitial nephritis. The development of renal pathology was unexpected but may be related to chronically elevated steroids since hydronephrosis has been observed in rats chronically administered estradiol (29). In addition, hydronephrosis is well documented during pregnancy in women and nonhuman primates, although it is disputed whether this results from ureteral obstruction or from physiologic dilatation due to elevated progesterone (30 (3,4), the impact of elevated LH levels on the fertilization of the oocyte and subsequent pregnancy should be studied.…”

Effect of Estrogen on the Formation of Struvite Calculi in Female Rats

“…Although correlation of UTI with estrogen has been reported by many investigators in the human [24,25], the dog [10], the rat [8,9], the lamb [11,12] and the mink [16,26], the mechanisms of estrogen action on the increase in susceptibility to UTI arc uncertain. Morpho logical changes of the urogenital tract by estrogen may be responsible for the increased susceptibility to UTI.…”

Pathologic changes in the human urinary tract due to anovulatory drug administration

“…(McNellis and Sherline, 1967) Histologic changes in the mucosa similar to those produced in pregnancy, namely an increase in glycogen laden cells, was present in the rabbit study, (McNellis and Sherline, 1967) and squamous metaplasia was seen in the rats treated with either 17B estradiol (Corriere and Murphy, 1968) or diethylstilbestrol. (Andriole and Cohn, 1965) Species specificity and nonpharmacologic dosage is probably the reason for the discrepancies in these studies.…”

“…Gross hydroureter and hydronephrosis has been produced in female rats with 17B estradiol, (Corriere and Murphy, 1968) in female and male rats with diethylstilbestrol (Andriole and Cohn, 1965) and in male mice with estrogen (Gardner, 1935) but not in female rabbits treated with a norethynodrel-mestranol preparation. (McNellis and Sherline, 1967) Histologic changes in the mucosa similar to those produced in pregnancy, namely an increase in glycogen laden cells, was present in the rabbit study, (McNellis and Sherline, 1967) and squamous metaplasia was seen in the rats treated with either 17B estradiol (Corriere and Murphy, 1968) or diethylstilbestrol.…”