IR-A was elevated during the normal proliferative phase, and in endometrial hyperplasia and adenocarcinoma. The dramatic early rise of IR-A in normal endometrium indicates IR-A is the predominant isoform responsible for initial estrogen-independent endometrial proliferation as well as that of cancer. IR-B is elevated during the normal secretory phase when glucose uptake and glycogen synthesis support embryo development. Differing from other cancers, IR-B expression equals mitogenic IR-A in endometrial adenocarcinoma. Differential IR isoform expression suggests a distinct role for each in endometrial physiology and cancer.

The biological activity of insulin and the insulin-like growth factor (IGF) ligands, IGF-I and IGF-II, is based in part on the relative abundance and distribution of their target receptors: the insulin receptor (IR) splice variants A (IR-A) and B (IR-B) and IGF 1 receptor (IGF-1R). However, the relative quantity of all three receptors in human tissues has never been measured together on the same scale. Due to the high homology between insulin receptor (IR)-A and IR-B proteins and lack of antibodies that discern the two IR splice variants, their mRNA sequence is the most reliable means of distinguishing between the receptors. Hence, highly specific primers for IR-A, IR-B, and IGF-1R mRNA were designed to accurately detect all three receptors by quantitative RT-PCR and enable direct quantification of relative receptor expression levels. A standard concentration curve of cDNA from each receptor was performed. Assay specificity was tested using competition assays and postamplification analysis by gel electrophoresis and cloning. Forward and reverse primer concentrations were optimized to ensure equal efficiencies across primer pairs. This assay enables a specific molecular signature of IGF/insulin signaling receptors to be assayed in different tissues, cell types, or cancers.

Objective: To evaluate the feasibility of percutaneous approach, we prospectively compared our experience in percutaneous-assisted hysterectomy (PSS-H) with that in a series of laparoscopic hysterectomies (LPS-Hs). Methods: In this multicentric cohort study, from May 2015 to October 2017, 160 patients affected by benign and malignant gynecological conditions were considered eligible for minimally invasive surgery (MIS): 80 patients received PSS-H and 80 LPS-H. In each group, 30 cases of low-/intermediate-risk endometrial cancer were enrolled. For both groups, we documented preoperative outcomes, postoperative pain, and cosmetic outcomes. Results: No statistically significant differences were noted in baseline characteristics or operative time. We observed significant differences in estimated blood loss: median of 50 cc (PSS-H) and 100 cc (LPS-H) (p = 0.0001). In LPS-H, we reported 4 (5.0%) intraoperative complications and 1 (1.3%) in PSS-H. Thirty-day complications were 4 (5%) in PSS-H and 11 (13.8%) in LPS-H (p = 0.058). No significative differences were found in visual analog scale score, despite a relevant disparity in cosmetic outcome (p = 0.0001). For oncological cases, the 2 techniques had comparable intraand postoperative outcomes and oncological accuracy. Conclusions: In this study, we reported that PSS-H is comparable to LPS-H for intra-and perioperative outcomes and postoperative pain, while PSS-H seems to be superior in cosmetic outcomes and patient satisfaction. PSS-H may represent a valid alternative in ultra-MIS for benign gynecological conditions and low-/intermediate-risk endometrial cancer.

Girls with obesity are at increased risk of early puberty. Obesity is associated with insulin resistance and hyperinsulinemia. We hypothesized insulin plays a physiological role in pubertal transition, and super-imposed hyperinsulinemia due to childhood obesity promotes early initiation of puberty in girls. To isolate the effect of hyperinsulinemia from adiposity, we compared pre-pubertal and pubertal states in hyperinsulinemic, lean Muscle (M)-IGF-1R-lysine (K)-arginine (R) (MKR) mice to normoinsulinemic wild-type (WT), with puberty onset defined by vaginal opening (VO). Our results show MKR had greater insulin resistance and higher insulin levels (p< 0.05) than WT despite lower body weight (pɘ.0001) and similar IGF-1 levels (p=NS). Serum LH levels were higher in hyperinsulinemic MKR (p=0.005), and insulin stimulation induced an increase in LH levels in WT. VO was earlier in hyperinsulinemic MKR vs WT (pɘ.0001). When compared on the day of VO, kisspeptin expression was higher in hyperinsulinemic MKR vs WT (pɘ.05) and GnRH and IR isoform expression was similar (p=NS). Despite accelerated VO, MKR had delayed, disordered ovarian follicle and mammary gland development. In conclusion, we found that hyperinsulinemia alone without adiposity triggers earlier puberty. In our study, hyperinsulinemia also promoted dyssynchrony between pubertal initiation and progression, urging future studies in girls with obesity to assess alterations in transition to adulthood.