Post-natal ontogeny of stanniocalcin gene expression in rodent kidney and regulation by dietary calcium and phosphate.

BACKGROUND: Stanniocalcin (STC) is a polypeptide hormone first discovered in fish and more recently in mammals. In mammals, STC is produced in many tissues and does not normally circulate in the blood. In kidney and gut, STC regulates phosphate fluxes across the transporting epithelia, whereas in brain it protects neurons against cerebral ischemia and promotes neuronal cell differentiation. The gene is highly expressed in ovary and dramatically up-regulated during pregnancy and nursing. Gene expression also is high during mammalian embryogenesis, particularly in kidney where the hormone signals between epithelial and mesenchymal cells during nephrogenesis. METHODS: This study examined the patterns of STC gene expression and protein distribution in the mouse kidney over the course of post-natal development. Further, because STC is a regulator of renal phosphate transport, we also examined the effects of changing levels of dietary calcium and phosphate on renal levels of STC gene expression in adult rats. RESULTS: STC mRNA levels in the neonate kidney were found to be tenfold higher than adults. Isotopic in situ hybridization of neonate kidneys revealed that most, if not all, STC mRNA was confined to collecting duct (CD) cells, as is the case in adults. STC protein on the other hand was found in proximal tubule, thick ascending limb and distal tubules in addition to CD cells. This suggests that, as in adults, the more proximal nephron segments in neonates are targeted by CD-derived STC and sequester large amounts of hormone. The addition of 1% calcium gluconate to the drinking water significantly reduced STC mRNA levels in inner medullary CD cells of both males and females, but not those in the cortex and outer medulla. Placing animals on low phosphate diets also reduced STC mRNA levels, but uniquely in outer medullary and cortical CD cells, whereas a high phosphate diet increased transcript levels in the same regions. CONCLUSIONS: These findings suggest that STC may be of unique importance to neonates. They also suggest that changes in dietary calcium and phosphate can alter renal levels of STC gene expression, but that these effects vary between the early and late segments of the collecting duct.

Possible roles for stanniocalcin during early skeletal patterning and joint formation in the mouse.

Stanniocalcin (STC) is a polypeptide hormone discovered first in fish and more recently in mammals. In mammals, the gene is widely expressed and the hormone is, so far, known to be involved in regulating the transport of calcium or phosphate across renal and gut epithelia, and into neuronal cells. Gene expression is also high during development, and in an earlier study we mapped the temporal and spatial pattern of gene expression in the mouse urogenital system. Our data suggested that STC probably acted as a signaling molecule that was produced in mesenchyme cells and targeted to epithelial cell layers in both kidney and testes. Here we have examined STC mRNA and protein distributions between developmental stages E10.5 and E18.5 in the axial and appendicular skeleton. In the axial skeleton, STC was transiently expressed in a rostral-caudal fashion during vertebral development; protein appeared to be made in intervertebral disc mesenchyme cells and targeted to vertebral hypertrophic and prehypertrophic chondrocytes. By stage E18.5, the STC gene was active only in vertebral perichondrocytes. The pattern of expression in the appendicular skeleton was equally striking. Early in development, STC gene expression defined the initial lengths of bone primordia. The gene was expressed in mesenchyme cells at either ends of precartilaginous condensations defining future long bones and the secreted protein was targeted to the chondroblasts. Later on during joint formation, STC was highly expressed in interzone cells that defined all future joints. After cavitation, STC gene expression was greatest in perichondrocytes lining the joints. Underlying resting, proliferative and prehypertrophic chondrocytes appeared to be the targets of STC both during and after cavitation. Therefore, its pattern of expression was indicative of a role in early skeletal patterning and joint formation. Moreover, as occurs during urogenital development, it appeared that STC is made in undifferentiated mesenchyme cells and sequestered by those destined to differentiate.

Dynamic changes in stanniocalcin gene expression in the mouse uterus during early implantation.

Blastocyst implantation is accompanied by dramatic changes in gene expression to facilitate decidualization and remodelling of uterine architecture. Stanniocalcin (STC) is a new mammalian polypeptide hormone with roles in ion transport, reproduction and development. Here we report dynamic changes in STC mRNA and protein distributions in the early post-implantation mouse uterus. In the non-pregnant state, STC gene expression was confined to the uterine lumenal epithelium. Following implantation STC gene expression shifted to mesometrial stromal cells bordering the uterine lumen. Between E6.5-E8.5 expression shifted once more to cells of the mesometrial lateral sinusoids, and then declined thereafter. Intriguingly immunoreactive STC did not entirely co-localize with areas of high STC gene activity and instead appeared to accumulate in presumptive targets of the hormone (uterine epithelium, stromal and decidual cells, trophoblastic giant cells). STC is only the fourth gene identified as being expressed mesometrially in the uterus following implantation.

Stanniocalcin gene expression during mouse urogenital development: a possible role in mesenchymal-epithelial signalling.

Stanniocalcin (STC) is a polypeptide hormone first discovered in fish and more recently in mammals. In mammals, the STC gene is widely expressed and the hormone is involved in a variety of functions, but STC does not normally circulate in the blood. In both kidney and gut, STC regulates phosphate fluxes across the transporting epithelia, whereas in brain it protects neurons against cerebral ischemia and promotes neuronal cell differentiation. However, the gene is most highly expressed in ovary and expression is dramatically up-regulated by both pregnancy and nursing. STC mRNA levels are also high in the developing mouse embryo, but literally nothing is known of the tissue pattern of gene expression. Therefore, the aim of this study was to map the temporal and spatial patterns of gene expression during mouse embryologic development, starting with the urogenital system where the gene is so highly expressed in adults. STC mRNA was evident as early as E10.5 in both the mesonephros and genital ridge. Between E10.5 and 14.5 in developing kidney, STC was produced in undifferentiated mesenchyme cells and sequestered by ureteric bud epithelial cells that did not express the gene but nonetheless contained high levels of STC protein. Thereafter, the distribution pattern resembled that in adults such that gene expression predominated in collecting duct cells, whereas protein was present in most nephron segments. The pattern of gene expression during gonadal development was sexually dimorphic. In males, expression was first evident on E12.5 in interstitial mesenchyme cells surrounding the developing sex cords, whereas the protein accumulated in developing gonocytes within the sex cords that did not express the gene. This pattern became more pronounced over the course of gestation. In contrast, ovarian gene expression was only weakly evident during development. Collectively, the evidence suggests that in addition to its regulatory effects in adults, STC has novel and distinctive roles in the mesenchymal-epithelial interactions that are vital to normal organogenesis.

[Use of autologous veins and streptokinase in vascular complications after replantation of the right forearm]. / Pouzitie autovény a streptokinázy pri cievnych komplikáciach po replantácii pravého predlaktia.

The authors present the case-history of a 20-year-old worker with an amputation of the forearm in the distal third. After shortening of the bone by 2.5 cm and osteosynthesis by means of grooved splints the blood vessels of the forearm were reconstructed by means of three autoveins. After 12 hours venous and arterial thrombosis developed. During reoperation the thrombotic portions of the vessels were resected and were again reconstructed by means of new autovenous grafts. Streptokinase was instilled into the amputate via the ulnar artery. During the subsequent postoperative period no serious vascular complications developed. Lymphorrhea persisted for some two weeks. To achieve satisfactory function of the hand a corrective operation will be necessary.