Early human preantral follicles have relaxin and relaxin receptor (LGR7), and relaxin promotes their development.

The regulatory mechanisms of early follicle development are not clearly understood. Although relaxin is a peptide that controls cell proliferation and differentiation in many tissues, its role in human follicular development is unclear. In this study we cultured slices of human ovarian cortical tissue in the presence and absence of recombinant human relaxin. Ovarian tissue was obtained by biopsy during gynecological laparotomy or laparoscopy (14 women; mean age +/- sem, 29.0 +/- 6.1 yr; range, 17-37 yr). A significantly higher proportion of secondary follicles (14.5% vs. 5.0% in the control group; P < 0.01) and a significantly decreased proportion of primordial follicles (30.1% vs. 47.4% in the control group; P < 0.05) were found in tissues cultured with relaxin for 7 d. Immunocytochemical studies with the anti-C-peptide of prorelaxin and antirelaxin antibodies revealed the localization of relaxin in the oocyte and in flat pregranulosa and granulosa cells of primordial, primary, and secondary follicles. The presence of the relaxin receptor LGR7 was observed in flat pregranulosa and granulosa cells of primordial, primary, and secondary follicles by immunocytochemical and in situ hybridization analyses. These results suggest that relaxin plays a role through its receptor during the early stage of follicle development.

Relaxin-induced angiogenesis in ovary contributes to follicle development.

CD31-positive blood vessels increased in human ovarian cortical tissues cultured with relaxin than in tissues cultured without relaxin. The number of vWF-positive vessels counted in rat ovaries after relaxin injection (40.5 +/- 4.3) significantly increased compared to that in saline-injected rats (24.3 +/- 3.0). The proportion of primordial follicles was significantly decreased, that of primary follicles was significantly increased at 16 h, and that of early antral follicles was significantly increased at 24 h in rats after relaxin injection. These results suggest that relaxin may contribute to follicle development through the mechanism of angiogenesis in the ovary.

Inhibitory effects of octreotide on luminal cholecystokinin-releasing factor, plasma cholecystokinin, and pancreatic secretion in conscious rats.

INTRODUCTION: Luminal cholecystokinin-releasing factor (LCRF), purified from rat intestinal secretions, is an intraluminal regulator of cholecystokinin (CCK) secretion during bile and pancreatic juice diversion. AIM: Because the LCRF content was not influenced by intravenous administration of atropine or somatostatin, the inhibitory effect of a potent somatostatin analog octreotide on LCRF content, the plasma CCK level, and pancreatic secretion was examined. METHODOLOGY: Rats were prepared with bile and pancreatic cannulae and two duodenal cannulae and with an external jugular vein cannula. After 1.5-hour basal collection, bile and pancreatic juice was diverted for 2 hours, during which octreotide was infused intravenously or into the duodenal lumen. The changes in pancreatic secretion were recorded for 2 hours, and the plasma CCK level and LCRF content 2 hours after the treatment were measured. RESULTS: Bile and pancreatic juice diversion significantly increased pancreatic secretion and plasma CCK and LCRF levels. Intravenous infusion of octreotide (0.2 and 0.5 nmol/kg/hour) inhibited all parameters. Intraduodenal infusion of a lower dose of octreotide (33 nmol/kg/hour) inhibited pancreatic secretion, but did not inhibit CCK release or LCRF content. The higher doses (100 and 300 nmol/kg/hour) inhibited all parameters. CONCLUSION: Intravenous and intraduodenal administrations of octreotide inhibited CCK release and LCRF content and pancreatic secretion induced by bile and pancreatic juice diversion.

Increased production of urea hydrogen peroxide from Maillard reaction and a UHP-Fenton pathway related to glycoxidation damage in chronic renal failure.

Urea hydrogen peroxide (UHP) is a stable form of H(2)O(2) and cytotoxic agent. This study describes examination of UHP formation from collagen glycation and relevant glycoxidative damage in chronic renal failure (CRF). Renal fibers were incubated with 50 mM ribose in either serum ultrafiltrate or phosphate-buffered saline in the presence of various concentrations of urea. UHP was determined by a modified ferrous oxidation in xylenol orange (FOX) assay. The presence of urea resulted in an increase in the generation of UHP in a dose-dependent manner of urea in these incubation systems. Pentosidine levels analyzed by HPLC also increased in a dose-dependent manner of urea. Blocking experiments showed that pentosidine and carboxymethyllysine formation was significantly enhanced by hydroxyl radical generated from UHP via Fenton reaction. The renal and cardiac levels of UHP, pentosidine, and carboxymethyllysine in patients with CRF, including seven predialysis and eight hemodialysis subjects, were significantly higher than that in controls (n = 16). The renal and cardiac levels of UHP closely correlated with the levels of renal and cardiac pentosidine and carboxymethyllysine and inversely correlated with left ventricle ejection fraction in CRF patients. This study provides evidence, for the first time, that UHP can be produced from Maillard reaction. Increased UHP in chronic renal failure enhances the formation of pentosidine and carboxymethyllysine via Fenton reaction (UHP-Fenton pathway).

Immunohistochemical Localization of Chromostatin and Pancreastatin, Chromogranin A-Derived Bioactive Peptides, in Normal and Neoplastic Neuroendocrine Tissues.

Despite the widespread distribution of chromogranin A (CgA) in neuroendocrine tissues, the biological function of CgA has not yet been elucidated. The primary amino acid sequence of CgA, elucidated by cDNA analysis, has been revealed to include several pairs of basic amino acid residues that are homologous to the bioactive peptides, such as pancreastatin (PST) and chromostatin (CST). Using antibodies for human PST and CST, the immunohistochemical localization of these peptides was investigated in neuroendocrine tissues, including human pituitary glands, pancreas, adrenal medulla, various types of neuroendocrine neoplasms (13 pheochromocytomas, 10 medullary thyroid carcinomas, 11 pancreatic endocrine tumors, and 19 carcinoid tumors), and the cell line QGP-1N derived from human somatostatin-producing pancreatic endocrine tumor. Variable immunoreactive intensities of PST and CST were seen, but both peptides were detectable in all neuroendocrine tissues and in most of the neoplasms. Immunoreactivity for both PST and CST was observed in 100 and 73%, respectively, of pancreatic endocrine tumors, all pheochromocytomas, and 80 and 40%, respectively, of medullary thyroid carcinomas, as well as all nonrectal carcinoid tumors. In rectal carcinoids, cells immunoreactive for PST and CST were sparse. The distribution of PST and CST was similar to that of CgA, and it is considered that these peptides are simultaneously processed from CgA, and may play roles in autocrine and paracrine regulation on various hormones in addition to their previously known functions.