Studies on the Character of Hypothalamic GnRH Neurons and Kisspeptin Neurons Using Hypothalamic Cell Models

The hypothalamic-pituitary-gonadal (HPG) axis controls the hormonal network responsible for reproductive functions. In the past, hypothalamic gonadotropin-releasing hormone (GnRH) neurons have been positioned at the highest level in the HPG axis. After the discovery of the indispensable roles of hypothalamic kisspeptin in GnRH neurons, our understanding of the neuroendocrine regulation of the HPG axis was reconfirmed, and it is now recognized that hypothalamic kisspeptin neurons are positioned at the summit of the HPG axis. Accumulating evidence shows that kisspeptin neurons are responsible for the onset of puberty and sex steroid feedback mechanisms by modulating the activity of GnRH neurons. Furthermore, the identification of kisspeptin in the hypophyseal portal circulation suggests that this peptide has some direct roles in the pituitary gland. The detailed mechanisms underlying the regulation of GnRH by kisspeptin and the regulatory control of kisspeptin neurons are still largely unknown because of the limitations of the experimental models. The establishment of GnRH-expressing and kisspeptin-expressing cell models has enabled us to examine the character of these neuronal cells. In this chapter, we describe our in vivo studies examining the character of GnRH neurons and kisspeptin neurons in the hypothalamus using hypothalamic GnRH- and/or kisspeptin-expressing cell models

Gonadotropin-inhibitory hormone inhibits GnRH-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 cells

A neuropeptide that directly inhibits gonadotropin secretion from the pituitary was discovered in quail and named gonadotropin-inhibitory hormone (GnIH). The presence and functional roles of GnIH orthologs, RF-amide-related peptides (RFRP), that possess acommonC-terminal LPXRF-amide (X L or Q) motif have also been demonstrated in mammals. GnIH orthologs inhibit gonadotropin synthesis and release by acting on pituitary gonadotropes and GnRH neurons in the hypothalamus via its receptor (GnIH receptor). It is becoming increasingly clear that GnIH is an important hypothalamic neuropeptide controlling reproduction, but the detailed signaling pathway mediating the inhibitory effect of GnIH on target cells is still unknown. In the present study, we investigated the pathway of GnIH cell signaling and its possible interaction with GnRH signaling using a mouse gonadotrope cell line, LβT2 . First, we demonstrated the expression of GnIH receptormRNAin L T2 cells by RT-PCR. We then examined the inhibitory effects of mouse GnIH orthologs [mouse RFRP (mRFRP)] on GnRH-induced cell signaling events. We showed that mRFRP effectively inhibited GnRH-induced cAMP signaling by using a cAMP-sensitive reporter system and measuring cAMP levels, indicating that mRFRP function as an inhibitor of adenylate cyclase.Wefurther showed that mRFRP inhibited GnRH-stimulated ERK phosphorylation, and this effect was mediated by the inhibition of the protein kinase A pathway. Finally, we demonstrated that mRFRP inhibited GnRH stimulated gonadotropin subunit gene transcriptions and also LH release. Taken together, the results indicate that mRFRP function as GnIH to inhibit GnRH-induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/protein kinase A-dependent ERK activation in LβT2 cells.http://endo.endojournals.orgnf201

Comparative Retrospective Study of Tension-Free Vaginal Mesh Surgery, Native Tissue Repair, and Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse Repair

Introduction and Hypothesis. Many would argue that sacrocolpopexy is the standard surgical procedure for pelvic organ prolapse (POP), but other surgical techniques were proposed and practically applying to the patients with POP. In this study, we compared postoperative outcomes of three surgical methods for POP repair. Methods. We identified that 308 women who had undergone surgical repair of POP were followed up for at least 6 months. Recurrence rates of POP after tension-free vaginal mesh (TVM) surgery (n = 243), native tissue repair (NTR) (vaginal hysterectomy with colpopexy, anterior and posterior colpoplasty, or circumferential suturing of the levator ani muscles and apical repair by transvaginal sacrospinous ligament fixation (SSLF)) (NTR; n = 31), and laparoscopic sacrocolpopexy after subtotal hysterectomy (LSC; n = 34) were compared. Presence of mesh erosion was also recorded. Results. Patients who underwent LSC were significantly younger (65.32 ± 3.23 years) than those who underwent TVM surgery (69.61 ± 8.31 years). After TVM surgery, the rate of recurrence (over POP-Q stage II) was 6.17% (15/243) and was highest in patients with advanced POP. The recurrence rate in patients who underwent NTR procedure was 3.23% (1/34) and that in patients who underwent LSC was 11.76% (4/11). There was no statistically significant difference in the recurrence rate between the three types of surgery. There were 13 cases (5.35%) of mesh erosion after TVM surgery and none after LSC surgery. The risk of mesh erosion was correlated with having had total TVM surgery but not with patient age or POP stage. Repeat procedures were performed in 5 women (2.14%) who underwent TVM surgery and 1 (2.94%) who underwent LSC. No patient underwent repeat surgery after NTR. There was no statistically significant difference in the reoperation rate between the three types of surgery. Conclusion. Our study suggested that TVM surgery, NTR, and LSC have comparable outcomes as for the postoperative recurrence rate and mesh erosion. However, the outcomes of each technique need to be carefully evaluated over a long period of time

Comparison of Postoperative Short-Term Outcomes between Tension-Free Vaginal Mesh Surgery Using the Capio™ SLIM Suture Capturing Device and Conventional TVM Surgery for Pelvic Organ Prolapse

Aim. We compared the short-term effectiveness of tension-free vaginal mesh (TVM) surgery using the Capio SLIM suture capturing device and conventional TVM surgery for treatment of pelvic organ prolapse. Methods. We retrospectively compared postoperative pain, urinary function, and length of hospital stay between 7 patients who underwent TVM surgery using the Capio device and 9 patients who underwent conventional TVM surgery. Results. There was no significant between-group difference in mean age between the Capio TVM group and the conventional TVM group (76.0 ± 5.6 years and 72.5 ± 11.5 years) or in mean operating time (86.56 ± 23.33 min and 95.28 ± 23.88 min). Four of the 7 patients in the Capio TVM group could not sense the urge to urinate after removal of the urethral catheter, but all patients in the conventional TVM group did so. The volume of the first voluntary urination was significantly smaller in the Capio TVM group than that in the conventional TVM group (102.14 ± 80.57 mL versus 472.22 ± 459.43 mL). The mean residual urine volume after the first voluntary urination was greater in the Capio TVM group than that in the conventional TVM group (285.70 ± 233.82 mL versus 34.56 ± 73.31 mL). The number of catheter days and mean maximal volume of residual urine were significantly greater in the Capio TVM group. The mean postoperative hospital stay was 6.57 ± 1.83 days in the Capio TVM group and 3.2 ± 0.42 days in the conventional TVM group. Six patients who underwent Capio TVM surgery complained of deep-seated pain in the hip region. Conclusion. Urinary function may worsen postoperatively when the Capio TVM device is used in patients with pelvic organ prolapse