Cyclooxygenase-2 (COX-2) has been shown to be the primary enzyme responsible for prostaglandin production during inflammation but is absent in most tissues under normal physiological states. High levels of COX-2 expression have been observed in the macula densa and thick ascending limbs of fetal kidneys; this expression declines to minimal levels during renal maturation. We hypothesized that the neoplastic cells of renal cell carcinoma (RCC) may revert to high expression of COX-2, and we evaluated its expression in three spontaneous cases of canine RCC by using immunohistochemical methods. The neoplastic cells of two of the three cases exhibited moderate to marked COX-2 immunoreactivity. These results suggest that some canine renal cell carcinomas express high levels of COX-2, which may play a role in the modulation of neoplastic cell growth.

Cyclooxygenase (COX) exists in two related but unique isoforms, COX-1 and COX-2, and is suggested to have specific functions in different segments of the nephron. COX-2 knockout mice develop fatal nephropathy, which implies that this isoform is important during nephrogenesis. The histologic changes seen in the COX-2 knockout mice are similar to those observed in the kidneys of human fetuses exposed to non-steroidal anti-inflammatory drugs (NSAIDs) in the third trimester of pregnancy. However, only minimal amounts of COX-2 mRNA or protein have been reported in the adult human kidney. We hypothesized that expression of COX-2 is significant in the fetal human kidney and that it is involved in the development of the nephron. To characterize the presence of COX-2 in the human fetal kidney, we used immunohistochemistry to evaluate its expression in 23 fetal kidneys ranging between 15 and 23 weeks of gestational age. Strong expression of COX-2 was localized primarily in the macula densa and the thick ascending limb of the loop of Henle, and in rare glomerular podocytes and vascular endothelial cells. There was a progressive decrease in COX-2 immunoreactivity from the most immature nephrons adjacent to the metanephric regions to the well-developed nephrons in the middle to inner cortex. In contrast to the adult human kidney, this temporal and spatial expression of COX-2 in the fetal kidney suggests that this enzyme may be involved in nephrogenesis, and its inhibition by NSAIDs during the third trimester may be responsible for fetal renal syndromes.

No COX-2 expression was seen in fetal tissues at days 7-13 of gestation, but was seen in various tissues at days 15-17 of gestation. These observations suggest that COX-2 may be important in mid to late pregnancy through an effect on fetal organ growth, but not in the organogenetic phase of fetal development.

Young of short-day-responsive (SDR/Y) and short-day-nonresponsive (SDNR/Y) Siberian hamsters were reared in a long (16L:8D) photoperiod. At weaning, males from both lineages were maintained in 16L:8D or transferred to a short (12L:12D) photoperiod; body weight and testis size were measured every 7-10 days until 45 or 140 days of age. Contrary to expected results, juvenile SDNR/Ys responded to the inhibitory effects of the shorter photoperiods with decreased body weight and inhibited testicular growth. Under the long photoperiods, SDR/Y and SDNR/Y animals exhibited accelerated body weight gains and testicular growth from 18 to 69 days of age. Beginning at 69 days of age, however, SDNR/Ys exhibited a transient decrease in testis size that troughed at 86 days of age; testis growth subsequently resumed. Consistent with their ability to respond to short photoperiods, SDNR/Y young, in a second experiment, showed locomotor activity patterns similar to those of SDR/Ys in short days (9L:15D). It was only in adult SDNR/Ys that the delayed onset of activity characteristic of nonresponders was apparent. These results indicate that the circadian system of nonresponders changes with age, rendering animals nonresponsive to short photoperiods. The period of transient testicular decline observed in SDNR/Ys housed in 16L:8D may mark a critical period in the onset of these changes; additional studies are required to test this hypothesis.

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