Leptin stimulates growth hormone secretion via a direct pituitary effect combined with a decreased somatostatin tone in a median eminence-pituitary perifusion study

The aim of this study was to examine the effect of recombinant human leptin on growth hormone (GH) secretion in perifused anterior pituitary slices from adult pigs. Anterior pituitary slices from sows were perifused and treated with recombinant human leptin (10 nM) and GH-releasing hormone (GHRH; 1 nM). In some experiments, pituitary slices were coincubated with stalk median eminence (SME). In a subset of the coincubation experiments, immunoneutralization of endogenous GHRH and somatostatin (SRIH) release was performed with antisera to GHRH and SRIH. Leptin increased GH secretion in pituitary slices alone (up to 100% vs. control at 40 min) as well as in pituitary slices coincubated with SME (up to 122% vs. control at 40 min). A significant difference was observed in GH secretion from pituitary slices when the tissue was coincubated with leptin and GHRH at a low concentration (0.1 nM), but not when GHRH was used at 1 and 10 nM. Furthermore, anti-SRIH antiserum increased GH release from pituitary slices in coincubation experiments with SME. Finally, SRIH secretion was significantly reduced by leptin (down by 35% vs. control from 0 to 30 min of treatment) in cultured SME. These data show that leptin is effective in stimulating GH secretion by acting at two different levels: (1) it stimulates GH secretion directly from pituitary slices, and (2) it reduces SRIH tone from the median eminence and, indirectly, increases GH secretion from the pituitary. These results support the hypothesis that leptin may be an interesting hormonal mediator of growth and related metabolic effects by acting directly on the hypothalamic-pituitary axis.     

Macroplastique implantation system for the treatment of female stress urinary incontinence

PURPOSE: We evaluated the 12-month followup outcome of the Macroplastique (Uroplasty, Minneapolis, Minnesota) implantation system for the treatment of stress urinary incontinence caused by intrinsic sphincter deficiency using objective and subjective measures, including quality of life impact. MATERIALS AND METHODS: A total of 21 consecutive women with a mean age of 47.4 years and a mean body mass index of 25.65 kg./m.2 in whom intrinsic sphincter deficiency was urodynamically diagnosed were enrolled in the study. Patients were preoperatively assessed by physical examination, quality of life questionnaire, Stamey grading of incontinence, pad use, pad weight test and urodynamic testing. Patients underwent periurethral injection under local anesthesia with the Macroplastique implantation system. The mean volume of silicone elastomers injected was 6.3 ml. RESULTS: As assessed by the King health questionnaire, patient quality of life improved in all domains and in most lower urinary tract symptoms. Patient satisfaction and subjective surgeon evaluation were assessed by Stamey incontinence grading. From patient point of view 12 (57.1%) considered themselves cured, 4 (19%) were improved and 5 (23.8%) had failure. According to subjective surgeon grading 8 patients (38.1%) were considered cured 6 (28.6%) were improved and 7 (33.3%) had failure. Pad use decreased from a mean of 4.38 to 1.29 units daily. According to the pad weight test 13 patients (62%) were dry, 4 (19%) were improved and 4 (19%) had failure. Urodynamic testing demonstrated that 8 patients (40%) were dry and 1 (5%) was improved. CONCLUSIONS: The Macroplastique implantation system proved to have an acceptable outcome for patient and surgeon. The procedure can be done with local anesthesia and without cystoscopic guidance.     

Effect of melatonin on the in vitro secretion of progesterone and estradiol 17 beta by ovine granulosa cells.

This study was undertaken to determine the effect of melatonin on steroid hormone production by ovine granulosa and luteal cells in vitro. Granulosa and luteal cells from ovine ovaries were cultured for nine days either in D-MEM only or in the presence of melatonin (0.86, 8.6, 86 nmol/l), ovine luteinizing hormone (oLH, 2 micrograms/l) or a combination of both these hormones. Progesterone (P4) and estradiol 17 beta (E2) were determined by validated RIAs. Melatonin stimulation began at either day 1 or day 5 of culture. Melatonin (0.86 nmol/l) significantly increased (p < 0.001) progesterone secretion by granulosa cells both when administered alone and when administered in combination with oLH; the more marked response was observed in the latter case. When the stimulation began at day 5, at a more advanced degree of differentiation of the cells, higher levels of P4 were observed. Higher concentrations of melatonin did not further increase progesterone production. Melatonin alone did not have a significant effect on the production of estradiol 17 beta; neither did melatonin stimulate progesterone production in either long-term cultured luteal cells or in short-term (1-2 h) cultured luteal and granulosa cells. The results of this study document a direct effect of melatonin in stimulating granulosa cells to produce progesterone, a synergistic activity between melatonin and luteinizing hormone and a different ability of granulosa cells to secrete P4 depending on the degree of differentiation.