The homologous regulation of pituitary Gonadotropin Releasing Hormone Receptor (GnRH-R) mRNA expression by GnRH has been well demonstrated. However, the regulation of the ovarian GnRH-R is poorly understood. The present study was performed to demonstrate the presence of GnRH transcripts in addition to GnRH-R mRNA and the regulation of GnRH-R mRNA expression in the granulosa cells isolated from small antral follicles. The GnRH and GnRH-R mRNA levels were determined by a competitive reverse transcription-polymerase chain reaction (RT-PCR). The granulosa cells were obtained from immature rats implanted with diethylstilbestrol for 3 days. When GnRH transcript expression was examined in isolated granulosa cells by RT-PCR, the PCR products showed two bands. The larger band contained intronic sequences and the smaller band was a fully processed GnRH gene transcript identical to hypothalamic GnRH. This suggests that authentic GnRH gene transcripts are expressed in ovarian granulosa cells and may act on the granulosa cells in a paracrine or autocrine manner. Since GnRH action in the granulosa cells is mediated by specific GnRH-R, it is of interest to examine whether GnRH-R is synthesized in the granulosa cells. When the granulosa cells were cultured in media only, GnRH-R mRNA levels increased abruptly within 3 h and gradually decreased thereafter during the 24 h culture period. However, GnRH itself did not alter the GnRH-R mRNA expression levels in cultured granulosa cells. Interestingly, treatment with FSH decreased the GnRH-R mRNA levels in a dose-dependent manner. A time-course analysis revealed that the GnRH-R mRNA levels were significantly lower up to 9 h after FSH treatment, and returned to the basal level between 12 h-24 h. Activation of adenylate cyclase with forskolin also decreased the GnRH-R mRNA levels. It is therefore concluded that in the granulosa cells of the small antral follicles GnRH-R mRNA expression was not homologously regulated by GnRH, while FSH may negatively regulate GnRH-R mRNA expression in the granulosa cells possibly through a cAMP-protein kinase A pathway.
Animal ; Cells, Cultured ; FSH/pharmacology ; Female ; Gene Expression Regulation* ; Gonadorelin/pharmacology ; Granulosa Cells/metabolism* ; Granulosa Cells/drug effects ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Receptors, LHRH/genetics* ; Reverse Transcriptase Polymerase Chain Reaction

Abdominal Muscles ; Adipose Tissue ; Artificial Intelligence ; Dataset ; Intra-Abdominal Fat ; Learning ; Muscle, Skeletal ; Muscles ; Sarcopenia ; Spine ; Subcutaneous Fat ; Tomography, X-Ray Computed

Purpose: We evaluated the association of body composition with long-term oncologic outcomes innon-metastatic rectal cancer patients. Materials and Methods: We included 1,384 patients with stage(y)0-III rectal cancer treated at Asan Medical Centerbetween January 2005 and December 2012. Body composition at diagnosis was measuredusing abdomino-pelvic computed tomography (CT). Sarcopenia, visceral obesity (VO), andsarcopenic obesity (SO) were defined using CT measured parameters such as skeletal muscleindex (total abdominal muscle area, TAMA), visceral fat area (VFA), and VFA/TAMA. Inflammatorystatus was defined as a neutrophil-lymphocyte ratio of ! 3. Obesity was categorizedby body mass index (! 25 kg/m2). Results: Among the 1,384 patients, 944 (68.2%) had sarcopenia and 307 (22.2%) had SO. The5-year overall survival (OS) rate was significantly lower in sarcopenic patients (no sarcopeniavs. sarcopenia; 84% vs. 78%, p=0.003) but the 5-year recurrence-free survival (RFS) ratewas not different (77.3% vs. 77.9% p=0.957). Patients with SO showed lower 5-year OS(79.1% vs. 75.5% p=0.02) but no difference in 5-year RFS (p=0.957). Sarcopenia, SO, VO,and obesity were not associated with RFS. However, obesity, SO, age, sex, inflammatorystatus, and tumor stage were confirmed as independent factors associated with OS on multivariateanalysis. In subgroup analysis, association of SO with OS was more prominent inpatients with (y)p stage 0-2 and no inflammatory status. Conclusion The presence of SO and a low body mass index at diagnosis are negatively associated withOS in non-metastatic rectal cancer patients.