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The Role of Gonadotropin-Releasing Hormone (GnRH) Agonists in the Treatment of Uterine Fibroids
Published in John C. Petrozza, Uterine Fibroids, 2020
Whitney A. Leonard, Alexander M. Quaas
GnRH is relatively dormant during childhood and attains its normal pulsatile nature in puberty. This pulsatile release continues throughout the reproductive years and menopause. Its short duration of action and pulsatile release allows continuous GnRH-agonist therapy to desensitize pituitary receptors and downregulate the HPO axis. Amino acid substitution at position six of the decapeptide has allowed for biologically active analogues of GnRH [1,8]. Further substitutions and additions have led to the creation of over 2000 GnRH analogues since its isolation in 1971. New research has revealed that kisspeptin, a polypeptide that binds to a G-protein-coupled receptor in the hypothalamus, plays a central role in the control of GnRH secretion [9]. Mutations in kisspeptin may be involved in the pathogenesis of disease, and research is ongoing to understand the kisspeptin–GnRH relationship and its impact on human endocrinology and disease [10].
Prior Elicitation
Published in Emmanuel Lesaffre, Gianluca Baio, Bruno Boulanger, Bayesian Methods in Pharmaceutical Research, 2020
Nicky Best, Nigel Dallow, Timothy Montague
Kinnersley (2015, Chapter 5) gives a detailed description of an elicitation carried out using the SHELF protocol to elicit parameters of a logistic dose-response model for an academic trial of kisspeptin as a potential treatment for in vitro fertilization (IVF). The aim of the elicitation was to generate prior information to help inform recommendations of alternative study designs that could provide similar information with fewer patients or provide answers to additional questions that would improve the design of subsequent Phase II or III trials. The logistic dose-response model for a binary response variable Yi given dose xi (i = 1, …, n) is given by
Endocrine Functions of Brain Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Kisspeptins are a group of peptides ranging from 10 to 54 amino acids that are derived from a single precursor. They bind to and activate the G protein-coupled receptor Kiss1R with similar efficacy [68]. The hypothalamic kisspeptin neurons play a key role in regulating the activity of GnRH neurons [69]. In both rodents and sheep, the kisspeptin neurons in the preoptic area are sexually dimorphic, being more numerous in females than males. There are two major groups of kisspeptin cell bodies: a large number in the arcuate nucleus, and a smaller number in the periventricular area of the third ventricle of rodents and the preoptic area of non-rodents [70].
Comparison of uterine, endometrial and subendometrial blood flows in predicting pregnancy outcomes between fresh and frozen-thawed embryo transfer after GnRH antagonist protocol: a retrospective cohort study
Published in Journal of Obstetrics and Gynaecology, 2023
Jianmei Yu, Bo Li, Haiyan Li, Qing Li, Zhen Nai, Bo Deng, Yunxiu Li
In recent years, GnRH antagonist protocol with high potency and fewer side effects has become increasingly popular in IVF/ICSI, having emerged as an alternative for preventing premature LH surges (Kadoura et al.2022). It has been confirmed that both GnRH and GnRH receptors are present in preimplantation embryos, fallopian tubes, ovary and endometrium (Tzoupis et al.2020), suggesting that GnRH antagonist appears to exist and have functional roles in multiple and diverse effects (Pousias et al.2019). GnRH can modulate matrix metalloproteinases and their endogenous inhibitors, tissue-specific inhibitors, which have an integral role in cyclic remodeling events in the endometrium for the implantation process. In addition, GnRH controlled the expression of kisspeptin (KISS1), which is related to the efficiency of assisted reproductive technology (D’Occhio et al.2020).
Chronic stress decreases fertility parameters in female rats
Published in Systems Biology in Reproductive Medicine, 2023
Fahiel Casillas, Alejandra Flores-González, Lizbeth Juárez-Rojas, Alma López, Miguel Betancourt, Eduardo Casas, Iván Bahena, Edmundo Bonilla, Socorro Retana-Márquez
In previously reported studies, our research group showed that in chronically stressed female rats, the stress produced alterations in the estrous cycle (prolonged proestrus and estrus; and absence of diestrus), decreased the number of pregnant females, as well as a decreased number of fetuses and increased fetal reabsorption (Retana-Márquez et al. 2020). These alterations were related to the effect that chronic stress has on negatively altering the hypothalamic-pituitary-ovary (HPO) axis. In this regard, it was reported that the levels of kisspeptin, GnRH, luteinizing hormone (LH), estradiol, and progesterone decrease mainly in the proestrus phase (Retana-Márquez et al. 2020), so this alteration of the HPO axis compromises the fertility of females. Subsequently, these results led us to evaluate the effect of chronic stress directly on the oocytes; it was found that their developmental potential is affected since there is a high percentage of dead and abnormal oocytes at all stages of the estrous cycle. It was also found that the number of in vivo mature oocytes significantly decreased in stressed females (Casillas et al. 2021) which would partially explain the affectation of female reproduction caused by stress. Therefore, in the present study, we aimed to evaluate the possible alterations by which the oocytes decrease their nuclear maturation. Several vital factors to achieve nuclear maturation were evaluated as well as other parameters in CCs.
Morphometric and Myelin Basic Protein Expression Changes in Arcuate Nucleus Kisspeptin Neurons Underlie Activation of Hypothalamic Pituitary Gonadal-axis in Monkeys (Macaca Mulatta) during the Breeding Season
Published in Endocrine Research, 2022
Hira Zubair, Shazia Shamas, Hamid Ullah, Ghulam Nabi, Tanzeel Huma, Rahim Ullah, Rashad Hussain, Muhammad Shahab
Changes in kisspeptin activity17 regulate the neurosecretory events of GnRH and pituitary gonadotropes. Intracerebroventricular (ICV) administration of kisspeptin in male mice evokes pituitary gonadotrope secretion even at very low doses.18 Similar effects were seen with peripheral kisspeptin administration in male19 and female rats.20 Similarly, kisspeptin administration resulted in acute luteinizing hormone (LH) response in Siberian hamsters during SD.10 Another study found that chronic kisspeptin administration reversed testicular atrophy in Syrian hamsters during SD.8 In the same line, kisspeptin administration induced ovulation in >80% anestrous sheep.21 These studies reinforce the physiological importance of the hypothalamic kisspeptin neuronal system in the seasonality of reproduction.