NADPH production by the pentose phosphate pathway in the zona fasciculata of rat adrenal gland

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was similar to 60%, 15%, and 7% of G6PD activity, respectively. The K-m value of G6PD for glucose-6-phosphate was two times higher than the K-m value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6P

Changes in the stage and surgical management of renal tumours during 1995-2005: an analysis of the Dutch national histopathology registry

OBJECTIVE: To evaluate changes in the pathological characteristics, stage of primary renal tumours and their surgical management in the Netherlands during the period 1995-2005. METHODS: Extracts from the records of all patients who had surgery for primary renal tumours in the Netherlands during the period 1995-2005 were reviewed. Data were collected from PALGA, the nationwide network and archive of histocytopathology. The 2002 Tumour-Node-Metastasis and the three-tier Fuhrman grade were used for staging and grading. RESULTS: In all there were 12 471 operations for primary renal masses during the study period. The incidence of surgically removed renal cancers increased from 6.2 in 1995 to 7.5 cases per 100 000 inhabitants (P = 0.005) in 2005. The mean (sd, median) age of the patients was 63.3 (11.9, 65.0) years, with a male-to-female ratio of 3:2. The mean (sd) tumour size of malignant tumours decreased from 7.3 (3.6) to 6.9 (3.7) cm (P = 0.301). The percentage of benign removed tumours remained relatively stable (P = 0.056), with a mean of 5.4% of all resected tumours. There was an increase of grade 1 tumours; the incidence of T1 tumours increased from 36.6% to 44.2%, and advanced tumours decreased from 46.4% to 33.7%, respectively. The percentage of nephron-sparing surgery increased from 3.5% in 1995 to 10.1% (P = 0.003) in 2005, mainly in the T1a tumours. CONCLUSIONS: During the last decade there was an increase in the incidence of surgically treated renal tumours in the Netherlands. Tumours with favourable histopathological characteristics, low stage and grade, accounted for most of this increase. The percentage of surgically removed benign tumours remained stable. The use of nephron-sparing surgery increased during the last decade, especially in T1a tumour

A Decade of Surgically Removed Small Renal Masses in The Netherlands: Characteristics and Trends in Type of Surgery and Pathologic Reporting

Purpose: To assess nationwide the pathologic characteristics and trends in type of surgery and pathologic reporting in surgically managed renal tumors = T-3). Tumors <= 3.0 cm were more likely to be benign (P = 0.006) and of lower stage (P = <0.001) than tumors of 3.1 to 4 cm. PN was performed in 16.5% of the cases. Grade and subtype were reported in 55% of the cases. The rate of PNs performed increased during the decade. There was a trend in increased reporting of grade and subtype. Conclusions: A quarter of all the operated primary kidney tumors were <= 4 cm. Smaller tumors were more likely to be benign and of lower stage. A cutoff size regarding biologic aggressiveness can be settled at the 3 cm size. The PN rate increased along the decade. Grade and subtype reporting rates remained suboptimal, although a positive trend was note