Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.
Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.
Project description:We used microarrays to detail the global program of gene expression underlying gonadotropin-releasing hormone (GnRH) generation and delamination from the olfactory placode.
Project description:GT1-7 cells were treated with 100 μg/mL HTR1A antagonist WAY-100635 maleate for 6 h and harvested for RNA-seq. This study aimed to investigate the expression of gonadotropin-releasing hormone and the differential expressed genes affected by HTR1A inhibition.
Project description:GT1-7 cells were treated with 100 μg/mL HTR1A antagonist WAY-100635 maleate for 6 h and harvested for investigation on the genome-wide enrichments of CBX4 and H2AK119ub by ChIP-seq. This study aimed to investigate the regulatory mechanism on expression of gonadotropin-releasing hormone affected by HTR1A inhibition.
Project description:Fertility critically depends on the gonadotropin-releasing hormone (GnRH) pulse generator, a neural construct comprised of hypothalamic neurons coexpressing kisspeptin, neurokoinin-B and dynorphin. Here, using mathematical modeling and in vivo optogenetics we reveal for the first time how this neural construct initiates and sustains the appropriate ultradian frequency essential for reproduction. Prompted by mathematical modeling, we show experimentally using female estrous mice that robust pulsatile release of luteinizing hormone, a proxy for GnRH, emerges abruptly as we increase the basal activity of the neuronal network using continuous low-frequency optogenetic stimulation. Further increase in basal activity markedly increases pulse frequency and eventually leads to pulse termination. Additional model predictions that pulsatile dynamics emerge from nonlinear positive and negative feedback interactions mediated through neurokinin-B and dynorphin signaling respectively are confirmed neuropharmacologically. Our results shed light on the long-elusive GnRH pulse generator offering new horizons for reproductive health and wellbeing.SIGNIFICANCE STATEMENT The gonadotropin-releasing hormone (GnRH) pulse generator controls the pulsatile secretion of the gonadotropic hormones LH and FSH and is critical for fertility. The hypothalamic arcuate kisspeptin neurons are thought to represent the GnRH pulse generator, since their oscillatory activity is coincident with LH pulses in the blood; a proxy for GnRH pulses. However, the mechanisms underlying GnRH pulse generation remain elusive. We developed a mathematical model of the kisspeptin neuronal network and confirmed its predictions experimentally, showing how LH secretion is frequency-modulated as we increase the basal activity of the arcuate kisspeptin neurons in vivo using continuous optogenetic stimulation. Our model provides a quantitative framework for understanding the reproductive neuroendocrine system and opens new horizons for fertility regulation
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
Project description:The process of ovulation includes oocyte meiotic maturation, follicle rupture and transformation of the follicle into a corpus luteum. These events are initiated by the midcycle surge of gonadotropins and require the coordinated regulation of thousands of genes. The aim of the study was to monitor the changes in granulosa cell gene expression across five different time points during the first 36 hours of ovulation until follicle rupture, in order to increase our understanding of the events of human ovulation. We conducted a prospective cohort study including women undergoing ovarian stimulation for fertility treatment. Women were treated in a standard antagonist protocol with individually dosed human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rFSH). Ovulation was induced with either recombinant hCG (rhCG) or gonadotropin releasing hormone agonist (GNRHa). The granulosa cells were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation (repeated measurements), and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 hours after OI.
Project description:<p>Introduction: Gonadotropin-releasing hormone (GnRH) is widely used in the timed artificial insemination program of sheep industry, but there is still controversy about the effect of GnRH on pregnancy rate in the process of artificial insemination. Our research shows that the use of GnRH reduces the pregnancy rate. This study aims to analyze the metabolite changes caused by GnRH in Huyang ewes before the implantation period through metabolomics technology, and reveal the mechanism behind the decreased pregnancy rate. </p><p>Methods: All ewes had a polyurethane sponge containing 45 mg of flurogestone acetate placed in their vagina for 12 days, and were intramuscularly treated with 330 units of equine chorionic gonadotropin (eCG) immediately after sponge removal. The experimental group (n = 69) received an intramuscular treatment of 17 μg GnRH agonist triptorelin (Day 0) 48 h after sponge removal, while the control group (n = 41) was treated with 1 mL of sterile saline. All ewes underwent a single vaginal insemination 58 h after the withdrawal of progesterone sponges. The difference in pregnancy rates between the two groups was then measured. Metabolomic analysis was performed on plasma samples collected on Day 7. </p><p>Results: Compared with the control group, GnRH treatment significantly reduced the pregnancy rate in the experimental group (72.2% vs 82.9%, P < 0.05). Metabolomic analysis revealed that GnRH treatment influenced metabolites involved in collagen synthesis and metabolites linked to prostaglandin synthesis in the endometrial tissue, which includes a marked decrease in hydroxyproline metabolite content and a substantial increase in corticosterone and prostaglandin D2 metabolite levels. </p><p>Conclusion: In summary, GnRH agonist Triptorelin injected 48 h after the withdrawal of progesterone sponges can reduce the pregnancy rate of Huyang ewe after artificial insemination and affect the metabolite levels related to endometrial collagen synthesis and prostaglandin synthesis, which are not conducive to embryo implantation.</p>