Leptin receptor expression in neoplastic and normal ovarian and endometrial tissue.

PURPOSE: The objective of this study was to investigate the expression of leptin receptors in benign and malignant tumors of the ovaries and endometrium and its association with body mass index (BMI). METHODS: Histological uterine and ovarian samples of normal and neoplastic tissue from 35 patients aged 37-72 years were examined for the expression of leptin receptors with the method of RT-PCR. T. RESULTS: A BMI > 30 was correlated with increased expression of leptin receptors. Both Ra and Rb receptors were expressed in normal and neoplastic tissues. A statistically significant difference in leptin receptor expression was detected between normal and neoplastic tissue, with expression being around 5-fold higher in neoplatic tissue. CONCLUSION: Endometrial neoplasms and long leptin isoform receptor expression were associated with an increased BMI. A role of long isoform in endometrial carcinogenesis is proposed.

Effect of an OT antagonist on the control of the midcycle LH surge in women.

OBJECTIVE: Data in women regarding the role of OT in LH secretion during the LH surge are conflicting. As in previous studies blood samples for LH measurements were taken infrequently, we re-examined this matter in women with a fully characterized midcycle LH surge. DESIGN: Normal women were studied over two cycles. When the dominant follicle reached a diameter of either 16-17 mm (Group 1) or 18-19 mm (Group 2), the women were infused intravenously for 3 h with normal saline (cycle-1) or atosiban (cycle-2). PATIENTS: Fifteen women (10 in group 1 and 5 in group 2) aged 23-35 years. MEASUREMENTS: Blood samples were obtained every 6 h to characterize the midcycle LH surge. RESULTS: The time interval (mean +/- SEM) from the start of the infusion to the onset of the LH surge in the two cycles was 46.8 +/- 4.8 and 45.6 +/- 9.6 h in group 1 and 6.0 +/- 2.4 and 7.5 +/- 2.8 h, respectively, in group 2. LH values during the LH surge were similar in the two cycles except in group 1 at the point of 30 h at which LH value in cycle-2 (41.2 +/- 4.6 mIU/ml) was significantly lower than in cycle-1 (52.8 +/- 3.4 mIU/ml, P < 0.05). Nevertheless, in each group, the area under the curve for LH was similar in the two cycles. CONCLUSIONS: Antagonism of endogenous OT action by atosiban does not alter the LH profile during a fully characterized midcycle LH surge, suggesting that OT is not a major regulator of LH secretion in women.

L1 (CAM) (CD171) in ovarian serous neoplasms.

PURPOSE OF THE INVESTIGATION: The evaluation of L1 (CAM) as a tumor progression marker and as a prognostic factor in serous ovarian tumors. METHODS: L1 (CAM) protein expression was assessed by immunohistochemistry and Western blot in serous ovarian tumors [cystadenomas (n = 20), borderline tumors (n = 14) and carcinomas (n = 47)], and was correlated with stage,grade, progression-free survival time (PFS) and overall survival. RESULTS: L1 (CAM) immunoreactivity correlated significantly with stage and grade. It increased from benign tumors to early carcinomas and to advanced stage carcinomas progressively and significantly. In Stage III G3 carcinoma patients, low L1 (CAM) expressing tumors exhibited better response to chemotherapy and were associated with statistically significantly longer PFS (p = 0.002). CONCLUSION: L1 (CAM) expression represents a novel diagnostic marker in serous ovarian neoplasms that shows characteristics of tumor progression. L1 expression was associated with chemotherapy response.

Oxytocin is not important for the control of gonadotrophin secretion in the late follicular phase of the cycle.

OBJECTIVE: To study the role of oxytocin in basal and GnRH-induced gonadotrophin secretion in normal women. DESIGN: Normal women were studied in three cycles. When the diameter of the leading follicle was 15-16 mm, the women were infused intravenously (i.v.) for 3 h with normal saline (cycle 1), atosiban (cycle 2) or oxytocin (cycle 3). PATIENTS: The study included 12 normally cycling women aged 23-38 years. MEASUREMENTS: After cessation of treatment, two injections of GnRH, 10 microg each, were administered i.v. 2 h apart and blood samples were collected every 30 min for a total of 240 min. The 30-min pituitary response (sensitivity) to a single GnRH injection (10 microg i.v.) was investigated thereafter every 12 h from the end of the 3-h infusion until the day of LH surge onset. RESULTS: No significant differences in LH and FSH response to GnRH (sensitivity and reserve) during the 240-min experiment were found between the three cycles. The time of LH surge onset from the initiation of the infusion was similar in the three cycles. Also similar in the three cycles were oestradiol (E2) and gonadotrophin levels as well as the 30-min response to GnRH for 48 h following the 3-h infusion. CONCLUSIONS: The present study demonstrates that neither exogenous oxytocin administration nor blockage of endogenous oxytocin action influences pituitary sensitivity to GnRH in cycling women.

Retinoid receptor alpha and Beta expression in serous ovarian tumors.

The expression of retinoid acid receptors alpha (RARalpha) and beta (RARbeta) and estrogen receptor alpha (ERalpha) was assessed by immunohistochemistry and Western blotting in normal ovaries, serous cystadenoma (n = 20), serous borderline (n = 14), and serous ovarian cancer (n = 47) and was correlated in cancer cases with stage, grade, progress-free survival (PFS), and survival. RARalpha was increasingly expressed in benign cystadenomas, borderline, and low-stage and advanced-stage neoplasms (p < 0.001). In stage III, G3 serous carcinoma, increased RARalpha expression was an independent prognostic factor associated with lower chemoresponse to first-line chemotherapy (taxol and carboplatin) and shorter PFS (p < 0.002).RARbeta and ERalpha expression did not correlate with RARalpha tumor characteristics or PFS and survival.

Evidence that termination of the estradiol-induced luteinizing hormone surge in women is regulated by ovarian factors.

BACKGROUND: The endogenous LH surge is the result of the estrogen-positive feedback effect. However, the factors that are responsible for the termination of LH surge are not known. OBJECTIVE: The objective of the study was to investigate the mechanism that terminates the LH surge in women. SUBJECTS AND METHODS: Eight normally cycling women (aged 42-48 yr) were investigated in two cycles, i.e. cycle 1 (control) and cycle 2. In cycle 2 total abdominal hysterectomy plus bilateral salpingooophorectomy was performed on d 3. In both cycles, estradiol was administered transdermally at the dose of 100 microg on d 3 and 150 microg on d 4 and 5. Blood samples were obtained every 12 h from d 3 to 5 and every 6 h thereafter until d 9. RESULTS: In both cycles, after suppression of gonadotropins, the women displayed an endogenous LH surge. The time intervals between the commencement of estradiol treatment and the LH surge onset (73.5 +/- 1.5 vs. 76.5 +/- 2.5 h) and peak LH values (11.4 +/- 1.9 vs. 12.4 +/- 3.1 IU/liter) were comparable in the two cycles (mean +/- sem). After peaking, LH values decreased gradually in cycle 1, whereas in cycle 2 they remained stable and were higher than the corresponding values in cycle 1 (P < 0.05). Before the LH surge onset, estradiol values showed in both cycles a preovulatory pattern of changes, but starting 24 h after the onset of the LH surge, they were lower in cycle 2 (P < 0.05). Progesterone levels were similar in both cycles until the day of the LH surge onset, but in cycle 2 they declined thereafter and were lower than in cycle 1 (P < 0.05). CONCLUSIONS: It is suggested that ovarian factors rather than exhaustion of pituitary reserves are important for termination of the endogenous LH surge during the normal menstrual cycle.