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Fertility and Sterility Jan 2004Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader...
Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
Topics: Clinical Trials as Topic; Female; Humans; Hyperandrogenism; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Risk Factors
PubMed: 14711538
DOI: 10.1016/j.fertnstert.2003.10.004 -
Drugs Aug 2022Linzagolix (Yselty) is an orally administered, selective, non-peptide small molecule gonadotrophin releasing hormone (GnRH) receptor antagonist that is being developed... (Review)
Review
Linzagolix (Yselty) is an orally administered, selective, non-peptide small molecule gonadotrophin releasing hormone (GnRH) receptor antagonist that is being developed by Kissei Pharmaceutical for the treatment of uterine fibroids and endometriosis in women of reproductive age. Linzagolix binds to and blocks the GnRH receptor in the pituitary gland, modulating the hypothalamic pituitary-gonadal axis and dose-dependently reducing serum luteinising hormone and follicle-stimulating hormone production and serum estradiol levels. In June 2022, linzagolix was approved for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age in the EU. Linzagolix is under regulatory review the USA for this indication and is in phase 3 clinical development in the treatment of pain associated with endometriosis. This article summarizes the milestones in the development of linzagolix leading to this first approval for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age.
Topics: Adult; Carboxylic Acids; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyoma; Luteinizing Hormone; Pharmaceutical Preparations; Pyrimidines; Receptors, LHRH
PubMed: 35997940
DOI: 10.1007/s40265-022-01753-9 -
Vitamins and Hormones 2021Fluctuations in luteinizing hormone (LH) release contribute to the development and maintenance of the reproductive system and become dysregulated during aging. Of note,... (Review)
Review
Fluctuations in luteinizing hormone (LH) release contribute to the development and maintenance of the reproductive system and become dysregulated during aging. Of note, increasing evidence supports extra-gonadal roles for LH within the CNS, particularly as it relates to cognition and plasticity in aging and age-related degenerative diseases such as Alzheimer's disease (AD). However, despite increasing evidence that supports a link between this hormone and CNS function, the mechanisms underlying LH action within the brain and how they influence cognition and plasticity during the lifespan is poorly understood and, in fact, often in conflict. This chapter aims to provide an up-to-date review of the literature addressing the role of LH signaling in the context of CNS aging and disease and put forward a unifying hypothesis that may explain currently conflicting theories regarding the role of LHCGR signaling in CNS function and dysfunction in aging and disease.
Topics: Aging; Brain; Cognition; Humans; Luteinizing Hormone; Neuronal Plasticity; Receptors, LH; Signal Transduction
PubMed: 33706966
DOI: 10.1016/bs.vh.2020.12.005 -
Frontiers in Endocrinology 2022
Topics: Fertility; Follicle Stimulating Hormone; Luteinizing Hormone
PubMed: 35992096
DOI: 10.3389/fendo.2022.991106 -
Molecular and Cellular Endocrinology Mar 2014Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy. Aside from the... (Review)
Review
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy. Aside from the timing of expression, however, the differences between LH and hCG have largely been overlooked in the clinical realm because of their similar molecular structures and shared receptor. With technologic advancements, including the development of highly purified and recombinant gonadotropins, researchers now appreciate that these hormones are not as interchangeable as once believed. Although they bind to a common receptor, emerging evidence suggests that LH and hCG have disparate effects on downstream signaling cascades. Increased understanding of the inherent differences between LH and hCG will foster more effective diagnostic and prognostic assays for use in a variety of clinical contexts and support the individualization of treatment strategies for conditions such as infertility.
Topics: Chorionic Gonadotropin; Female; Gene Expression Regulation; Humans; Infertility, Female; Luteinizing Hormone; Ovulation; Pregnancy; Protein Binding; Protein Subunits; Receptors, LH; Signal Transduction
PubMed: 24365330
DOI: 10.1016/j.mce.2013.12.009 -
Frontiers in Endocrinology 2022Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to... (Review)
Review
Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to stimulate follicular growth, and the mid-cycle luteinising hormone (LH) surge that leads to ovulation. E2 predominantly exerts its action oestrogen receptor-alpha (ERα), however, as gonadotrophin releasing hormone (GnRH) neurons lack ERα, E2-feedback is posited to be indirectly mediated upstream neurons. Kisspeptin (KP) is a neuropeptide expressed in hypothalamic KP-neurons that control GnRH secretion and plays a key role in the central mechanism regulating the hypothalamic-pituitary-gonadal (HPG) axis. In the rodent arcuate (ARC) nucleus, KP is co-expressed with Neurokinin B and Dynorphin; and thus, these neurons are termed 'Kisspeptin-Neurokinin B-Dynorphin' (KNDy) neurons. ARC KP-neurons function as the 'GnRH pulse generator' to regulate GnRH pulsatility, as well as mediating negative feedback from E2. A second KP neuronal population is present in the rostral periventricular area of the third ventricle (RP3V), which includes anteroventral periventricular (AVPV) nucleus and preoptic area neurons. These RP3V KP-neurons mediate positive feedback to induce the mid-cycle luteinising hormone (LH) surge and subsequent ovulation. Here, we describe the role of KP-neurons in these two regions in mediating this differential feedback from oestrogens. We conclude by considering reproductive diseases for which exploitation of these mechanisms could yield future therapies.
Topics: Kisspeptins; Neurokinin B; Dynorphins; Luteinizing Hormone; Gonadotropin-Releasing Hormone; Neurons
PubMed: 36479214
DOI: 10.3389/fendo.2022.951938 -
General and Comparative Endocrinology Dec 2021Changes in expression or activation of various metalloproteases including matrix metalloproteases (Mmp), a disintegrin and metalloprotease (Adam) and a disintegrin and... (Review)
Review
Changes in expression or activation of various metalloproteases including matrix metalloproteases (Mmp), a disintegrin and metalloprotease (Adam) and a disintegrin and metalloprotease with thrombospondin motif (Adamts), and their endogenous inhibitors (tissue inhibitors of metalloproteases, Timp), have been shown to be critical for ovulation in various species from studies in past decades. Some of these metalloproteases such as Adamts1, Adamts9, Mmp2, and Mmp9 have also been shown to be regulated by luteinizing hormone (LH) and/or progestin, which are essential triggers for ovulation in all vertebrate species. Most of these metalloproteases also express broadly in various tissues and cells including germ cells and somatic gonad cells. Thus, metalloproteases likely play roles in gonad formation processes comprising primordial germ cell (PGC) migration, development of germ and somatic cells, and sex determination. However, our knowledge on the functions and mechanisms of metalloproteases in these processes in vertebrates is still lacking. This review will summarize our current knowledge on the metalloproteases in ovulation and gonad formation with emphasis on PGC migration and germ cell development.
Topics: Animals; Female; Germ Cells; Gonads; Luteinizing Hormone; Matrix Metalloproteinases; Ovulation
PubMed: 34606745
DOI: 10.1016/j.ygcen.2021.113924 -
Endocrinology Jan 2019The hypothalamic decapeptide, GnRH, is the gatekeeper of mammalian reproductive development and function. Activation of specific, high-affinity cell surface receptors... (Review)
Review
The hypothalamic decapeptide, GnRH, is the gatekeeper of mammalian reproductive development and function. Activation of specific, high-affinity cell surface receptors (GnRH receptors) on gonadotropes by GnRH triggers signal transduction cascades to stimulate the coordinated synthesis and secretion of the pituitary gonadotropins FSH and LH. These hormones direct gonadal steroidogenesis and gametogenesis, making their tightly regulated production and secretion essential for normal sexual maturation and reproductive health. FSH and LH are glycoprotein heterodimers comprised of a common α-subunit and a unique β-subunit (FSHβ and LHβ, respectively), which determines the biological specificity of the gonadotropins. The unique β-subunit is the rate-limiting step for the production of the mature gonadotropins. Therefore, FSH synthesis is regulated at the transcriptional level by Fshb gene expression. The overarching goal of this review is to expand our understanding of the mechanisms and pathways underlying the carefully orchestrated control of FSH synthesis and secretion by GnRH, focusing on the transcriptional regulation of the Fshb gene. Identification of these regulatory mechanisms is not only fundamental to our understanding of normal reproductive function but will also provide a context for the elucidation of the pathophysiology of reproductive disorders and infertility to lead to potential new therapeutic approaches.
Topics: Animals; Female; Follicle Stimulating Hormone, beta Subunit; Gene Expression Regulation; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone
PubMed: 30517625
DOI: 10.1210/en.2018-00889 -
Molecular and Cellular Endocrinology Dec 2019Stress is well-known to inhibit a variety of reproductive processes, including the suppression of episodic Gonadotropin releasing hormone (GnRH) secretion, typically... (Review)
Review
Stress is well-known to inhibit a variety of reproductive processes, including the suppression of episodic Gonadotropin releasing hormone (GnRH) secretion, typically measured via downstream luteinizing hormone (LH) secretion. Since pulsatile secretion of GnRH and LH are necessary for proper reproductive function in both males and females, and stress is common for both human and animals, understanding the fundamental mechanisms by which stress impairs LH pulses is of critical importance. Activation of the hypothalamic-pituitary-adrenal axis, and its corresponding endocrine factors, is a key feature of the stress response, so dissecting the role of stress hormones, including corticotrophin releasing hormone (CRH) and corticosterone, in the inhibition of LH secretion has been one key research focus. However, some evidence suggests that these stress hormones alone are not sufficient for the full inhibition of LH caused by stress, implicating the additional involvement of other hormonal or neural signaling pathways in this process (including inputs from the brainstem, amygdala, parabrachial nucleus, and dorsomedial nucleus). Moreover, different stress types, such as metabolic stress (hypoglycemia), immune stress, and psychosocial stress, appear to suppress LH secretion via partially unique neural and endocrine pathways. The mechanisms underlying the suppression of LH pulses in these models offer interesting comparisons and contrasts, including the specific roles of amygdaloid nuclei and CRH receptor types. This review focuses on the most recent and emerging insights into endocrine and neural mechanisms responsible for the suppression of pulsatile LH secretion in mammals, and offers insights in important gaps in knowledge.
Topics: Animals; Endocrine System; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Nervous System; Stress, Physiological
PubMed: 31521706
DOI: 10.1016/j.mce.2019.110579 -
Fertility and Sterility Nov 2020Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the...
Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the first woman to be awarded a Tony for Best Direction of a Musical.
Topics: Female; Gynecology; Humans; Luteinizing Hormone; Ovulation; Ovulation Induction
PubMed: 32819679
DOI: 10.1016/j.fertnstert.2020.07.041