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Search results for: Native Human LHRH Proteins

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#37925096   2023/11/03 To Up

Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals.

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 can induce oocyte maturation during in vitro fertilization treatment, including in women who are at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported.
Ali Abbara, Mike Ufer, Christine Voors-Pette, Lance Berman, Max Ezzati, Rui Wu, Tien-Yi Lee, Juan Camilo Arjona Ferreira, Elizabeth Migoya, Waljit S Dhillo

1424 related Products with: Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals.

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#37669732   2023/09/03 To Up

Update on the management of endometriosis-associated pain in France.

The French National College of Obstetricians and Gynecologists (CNGOF) published guidelines for managing endometriosis-associated pain in 2018. Given the development of new pharmacological therapies and a review that was published in 2021, most national and international guidelines now suggest a new therapeutic approach. In addition, a novel validated screening method based on patient questionnaires and analysis of 109-miRNA saliva signatures, which combines biomarkers and artificial intelligence, opens up new avenues for overcoming diagnostic challenges in patients with pelvic pain and for avoiding laparoscopic surgery when sonography and MRI are not conclusive. Dienogest (DNG) 2 mg has been a reimbursable healthcare expense in France since 2020, and, according to recent studies, it is at least as effective as combined hormonal contraception (CHC) and can be used as an alternative to CHC for first-line treatment of endometriosis-associated pain. Since 2018, the literature concerning the use of DNG has grown considerably, and the French guidelines should be modified accordingly. The levonorgestrel intrauterine system (LNG IUS) and other available progestins per os, including DNG, or the subcutaneous implant, can be offered as first-line therapy, gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (ABT) as second-line therapy. Oral GnRH antagonists are promising new medical treatments for women with endometriosis-associated pain. They competitively bind to GnRH receptors in the anterior pituitary, preventing native GnRH from binding to GnRH receptors and from stimulating the secretion of luteinizing hormone and follicle-stimulating hormone. Consequently, estradiol and progesterone production is reduced. Oral GnRH antagonists will soon be on the market in France. Given their mode of action, their efficacy is comparable to that of GnRH agonists, with the advantage of oral administration and rapid action with no flare-up effect. Combination therapy with ABT is likely to allow long-term treatment with minimal impact on bone mass. GnRH antagonists with ABT may thus be offered as second-line treatment as an alternative to GnRH agonists with ABT. This article presents an update on the management of endometriosis-associated pain in women who do not have an immediate desire for pregnancy.
Hervé Fernandez, Aubert Agostini, Hortense Baffet, Nathalie Chabbert-Buffet, Philippe Descamps, Jean-Philippe Estrade, Géraldine Giraudet, Claude Hocke, Bruno Salle, Florence Tremollieres, Charles Chapron

1863 related Products with: Update on the management of endometriosis-associated pain in France.

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#36336621   2022/10/14 To Up

Low-dose every-second-day LHRH treatment following bilateral orchidopexy in children with bilateral cryptorchidism may improve their fertility outcome.

Currently the standard treatment for bilateral cryptorchidism is bilateral surgical orchidopexy. Whether a hormonal treatment should be routinely administered postoperatively to increase fertility is debatable. Low-dose postoperative luteinizing hormone releasing hormone (LHRH) can increase spermatogonial numbers, but the effect of native LHRH (Kryptocur®) on adult fertility is unclear.
Guy Bogaert, Michael Vanhoyland, Faruk Hadziselimovic

1846 related Products with: Low-dose every-second-day LHRH treatment following bilateral orchidopexy in children with bilateral cryptorchidism may improve their fertility outcome.

100 ul250 mg100 mg100 μg100μg100100 μg100ug Lyophilized

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#34620727   2021/10/07 To Up

Transgender Youth Referred to Clinics for Gender-Affirming Medical Care in Canada.

Referrals of transgender and gender-diverse (trans) youth to medical clinics for gender-affirming care have increased. We described characteristics of trans youth in Canada at first referral visit.
Greta R Bauer, Danièle Pacaud, Robert Couch, Daniel L Metzger, Lorraine Gale, Sandra Gotovac, Arati Mokashi, Stephen Feder, Joe Raiche, Kathy Nixon Speechley, Julia Temple Newhook, Shuvo Ghosh, Annie Pullen Sansfaçon, Françoise Susset, Margaret L Lawson,

2578 related Products with: Transgender Youth Referred to Clinics for Gender-Affirming Medical Care in Canada.

500 gm.100 100 G250 mg100 96 wells (1 kit) 1 G

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#34210598   2021/06/29 To Up

Clinical Potential of Kisspeptin in Reproductive Health.

Kisspeptins are a family of hypothalamic neuropeptides that are essential for the regulation of reproductive physiology. Their importance in reproductive health became apparent in 2003, when loss-of-function variants in the gene encoding the kisspeptin receptor were reported to result in isolated congenital hypogonadotropic hypogonadism (CHH). It has since been ascertained that hypothalamic kisspeptin neurons regulate gonadotropin-releasing hormone (GnRH) secretion to thus stimulate the remainder of the reproductive endocrine axis. In this review, we discuss genetic variants that affect kisspeptin receptor signaling, summarize data on KISS1R agonists, and posit possible clinical uses of native and synthetic kisspeptin receptor agonists for the investigation and treatment of reproductive disorders.
Ali Abbara, Sophie A Clarke, Waljit S Dhillo

1205 related Products with: Clinical Potential of Kisspeptin in Reproductive Health.



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#34188064   2021/06/29 To Up

Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts.

Different strategies are used to meet optimal reproductive performance or manage reproductive health. Although exogenous human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonists (A) are commonly used to trigger ovulation in estrous cycle synchronization, little is known about their effect on the ovarian follicle. Here, we explored whether hCG- and GnRH-A-induced native luteinizing hormone (LH) can affect the endocrine and molecular milieus of ovarian preovulatory follicles in pigs at different stages of sexual development. We collected ovaries 30 h after hCG/GnRH-A administration from altrenogest and pregnant mare serum gonadotropin (eCG)-primed prepubertal and sexually mature gilts. Several endocrine and molecular alternations were indicated, including broad hormonal trigger-induced changes in follicular fluid steroid hormones and prostaglandin levels. However, sexual maturity affected only estradiol levels. Trigger- and/or maturity-dependent changes in the abundance of hormone receptors (FSHR and LHCGR) and proteins associated with lipid metabolism and steroidogenesis (e.g., STAR, HSD3B1, and CYP11A1), prostaglandin synthesis (PTGS2 and PTGFS), extracellular matrix remodeling (MMP1 and TIMP1), protein folding (HSPs), molecular transport (TF), and cell function and survival (e.g., VIM) were observed. These data revealed different endocrine properties of exogenous and endogenous gonadotropins, with a potent progestational/androgenic role of hCG and estrogenic/pro-developmental function of LH.
Adam J Ziecik, Jan Klos, Katarzyna Gromadzka-Hliwa, Mariola A Dietrich, Mariola Slowinska, Pawel Likszo, Katarzyna Knapczyk-Stwora, Zdzislaw Gajewski, Monika M Kaczmarek

1436 related Products with: Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts.

1 ml1 kit(96 Wells)1 kit(96 Wells)96/kit200 1000 1 mg0.1 mg100ul25 mg 5 G

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#33824966   // To Up

Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB.

FSH is critical for fertility. Transcription of FSHB, the gene encoding the beta subunit, is rate-limiting in FSH production and is regulated by both GnRH and activin. Activin signals through SMAD transcription factors. Although the mechanisms and importance of activin signaling in mouse Fshb transcription are well-established, activin regulation of human FSHB is less well understood. We previously reported a novel enhancer of FSHB that contains a fertility-associated single nucleotide polymorphism (rs10031006) and requires a region resembling a full (8 base-pair) SMAD binding element (SBE). Here, we investigated the role of the putative SBE within the enhancer in activin and GnRH regulation of FSHB. In mouse gonadotrope-derived LβT2 cells, the upstream enhancer potentiated activin induction of both the human and mouse FSHB proximal promoters and conferred activin responsiveness to a minimal promoter. Activin induction of the enhancer required the SBE and was blocked by the inhibitory SMAD7, confirming involvement of the classical SMAD signaling pathway. GnRH induction of FSHB was also potentiated by the enhancer and dependent on the SBE, consistent with known activin/GnRH synergy regulating FSHB transcription. In DNA pull-down, the enhancer SBE bound SMAD4, and chromatin immunoprecipitation demonstrated SMAD4 enrichment at the enhancer in native chromatin. Combined activin/GnRH treatment elevated levels of the active transcriptional histone marker, histone 3 lysine 27 acetylation, at the enhancer. Overall, this study indicates that the enhancer is directly targeted by activin signaling and identifies a novel, evolutionarily conserved mechanism by which activin and GnRH can regulate FSHB transcription.
Stephanie C Bohaczuk, Jessica Cassin, Theresa I Slaiwa, Varykina G Thackray, Pamela L Mellon

2620 related Products with: Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB.

1 g100ugKIT 30 ml 96 wells (1 kit)100ug100.00 ug2ug100ug1 mg100ug Lyophilized100ug

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#33196464   // To Up

Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.

BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODSWe conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTSIn healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSIONTaken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATIONInternational Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDINGNational Institute for Health Research and NIH.
Ali Abbara, Pei Chia Eng, Maria Phylactou, Sophie A Clarke, Rachel Richardson, Charlene M Sykes, Chayarndorn Phumsatitpong, Edouard Mills, Manish Modi, Chioma Izzi-Engbeaya, Debbie Papadopoulou, Kate Purugganan, Channa N Jayasena, Lisa Webber, Rehan Salim, Bryn Owen, Paul Bech, Alexander N Comninos, Craig A McArdle, Margaritis Voliotis, Krasimira Tsaneva-Atanasova, Suzanne Moenter, Aylin Hanyaloglu, Waljit S Dhillo

2106 related Products with: Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.

5 mg100 8 inhibitors100ul2000 rxn100ug Lyophilized100ug Lyophilized100ug Lyophilized1,000 tests50ug

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#31614426   2019/10/11 To Up

Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers.

Head and neck squamous cell carcinomas (HNSCC) have a high mortality rate, although several potential therapeutic targets have already been identified. Gonadotropin-releasing hormone receptor (GnRH-R) expression is less studied in head and neck cancers, hence, we investigated the therapeutic relevance of GnRH-R targeting in HNSCC patients. Our results indicate that half of the patient-derived samples showed high GnRH-R expression, which was associated with worse prognosis, making this receptor a promising target for GnRH-based drug delivery. Photodynamic therapy is a clinically approved treatment for HNSCC, and the efficacy and selectivity may be enhanced by the covalent conjugation of the photosensitizer to a GnRH-R targeting peptide. Several native ligands, gonadotropin-releasing hormone (GnRH) isoforms, are known to target GnRH-R effectively. Therefore, different Lys(Bu) modified GnRH analogs were designed and conjugated to protoporphyrin IX. The receptor binding potency of the novel conjugates was measured on human pituitary and human prostate cancer cells, indicating only slightly lower GnRH-R affinity than the peptides. The cell viability inhibition was tested on Detroit-562 human pharyngeal carcinoma cells that express GnRH-R in high levels, and the results showed that all conjugates were more effective than the free protoporphyrin IX.
Lilla Pethő, József Murányi, Kinga Pénzes, Bianka Gurbi, Diána Brauswetter, Gábor Halmos, Gabriella Csík, Gábor Mező

1079 related Products with: Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers.

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#31084750   2019/03/21 To Up

Enhancing Fertility in Mares: Recombinant Equine Gonadotropins.

Advanced reproductive technologies have been developed to enhance fertility in mares and stallions. Some of these technologies in mares include superovulation, embryo transfer (ET), intracytoplasmic sperm injection (ICSI), oocyte transfer (OT), gamete intrafallopian transfer (GIFT), and cloning. Superovulation can provide multiple oocytes for these techniques. This review will focus on how recombinant equine follicle-stimulating hormone (reFSH) and recombinant equine luteinizing hormone (reLH) are important for superovulation and ET and may be useful for ICSI, OT, GIFT, and cloning. Superovulation would increase pregnancy rates in normal and subfertile mares and enhance reproductive efficiency when using semen from subfertile stallions. Superovulation depends on a timely interaction of gonadotropins and gonadal feedback in the mare. Historically, several hormone protocols have been used to manipulate follicular waves to increase development and ovulations in cycling, anestrous, and transitional mares. Attempts to superovulate cyclic mares or induce the first ovulation of the year in anestrous or transitional mares using preparations of equine chorionic gonadotropin, gonadotropin-releasing hormone (GnRH), GnRH agonists, porcine FSH, domperidone, sulpiride, equine pituitary extracts, native equine FSH, human chorionic gonadotropin, progesterone, and immunization against inhibin have produced variable results. The use of recombinant technology has improved the ability to produce a reliable product in substantial quantities that is free of other hormones and possible contaminants. Several studies using reFSH and reLH that demonstrate their efficacy to superovulate the mare and induce the first ovulation of the year will be discussed in this review.
Janet F Roser, Geraldine Meyers-Brown

1609 related Products with: Enhancing Fertility in Mares: Recombinant Equine Gonadotropins.



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