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Molecular and Cellular Endocrinology Mar 2018The precise orchestration of hormonal regulation at all levels of the hypothalamic-pituitary-gonadal axis is essential for normal reproductive function and fertility.... (Review)
Review
The precise orchestration of hormonal regulation at all levels of the hypothalamic-pituitary-gonadal axis is essential for normal reproductive function and fertility. The pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) stimulates the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotropes. GnRH acts by binding to its high affinity seven-transmembrane receptor (GnRHR) on the cell surface of anterior pituitary gonadotropes. Different signaling cascades and transcriptional mechanisms are activated, depending on the variation in GnRH pulse frequency, to stimulate the synthesis and release of FSH and LH. While changes in GnRH pulse frequency may explain some of the differential regulation of FSH and LH, other factors, such as activin, inhibin and sex steroids, also contribute to gonadotropin production. In this review, we focus on the transcriptional regulation of the gonadotropin subunit genes and the signaling pathways activated by pulsatile GnRH.
Topics: Animals; Gene Expression Regulation; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Models, Animal; Receptors, LHRH; Signal Transduction
PubMed: 29102564
DOI: 10.1016/j.mce.2017.10.015 -
Best Practice & Research. Clinical... Feb 2019Natural Cycle IVF (NC-IVF) with and without modifications is being increasingly performed. NC-IVF and conventional gonadotropin-stimulated IVF (cIVF) should not be... (Review)
Review
Natural Cycle IVF (NC-IVF) with and without modifications is being increasingly performed. NC-IVF and conventional gonadotropin-stimulated IVF (cIVF) should not be understood as competing treatments, but as complementary treatments with different target groups and to some extent other indications. NC-IVF is particularly interesting for couples who wish to save money, wish a treatment with as few risks as possible and for women who would like to avoid selection and cryopreservation of embryos. NC-IVF therefore contributes to the concept of individualized and patient-oriented therapy. The time to pregnancy is slightly longer than with conventional IVF. NC-IVF is particularly suitable for younger women and for women with a very low ovarian reserve. In this article, the principles of NC-IVF, i.e. monofollicular IVF without gonadotropin stimulation, are described and the technical differences to cIVF, advantages and disadvantages, perinatal outcome and indications for NC-IVF are highlightened.
Topics: Female; Fertilization in Vitro; Gonadotropins; Humans; Menstrual Cycle; Pregnancy; Reproductive Techniques, Assisted
PubMed: 30473207
DOI: 10.1016/j.beem.2018.10.005 -
Human Reproduction (Oxford, England) May 2021Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play complementary roles in follicle development and ovulation via a complex interaction in the... (Review)
Review
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play complementary roles in follicle development and ovulation via a complex interaction in the hypothalamus, anterior pituitary gland, reproductive organs, and oocytes. Impairment of the production or action of gonadotropins causes relative or absolute LH and FSH deficiency that compromises gametogenesis and gonadal steroid production, thereby reducing fertility. In women, LH and FSH deficiency is a spectrum of conditions with different functional or organic causes that are characterized by low or normal gonadotropin levels and low oestradiol levels. While the causes and effects of reduced LH and FSH production are very well known, the notion of reduced action has received less attention by researchers. Recent evidence shows that molecular characteristics, signalling as well as ageing, and some polymorphisms negatively affect gonadotropin action. These findings have important clinical implications, in particular for medically assisted reproduction in which diminished action determined by the afore-mentioned factors, combined with reduced endogenous gonadotropin production caused by GnRH analogue protocols, may lead to resistance to gonadotropins and, thus, to an unexpected hypo-response to ovarian stimulation. Indeed, the importance of LH and FSH action has been highlighted by the International Committee for Monitoring Assisted Reproduction Technologies (ICMART) in their definition of hypogonadotropic hypogonadism as gonadal failure associated with reduced gametogenesis and gonadal steroid production due to reduced gonadotropin production or action. The aim of this review is to provide an overview of determinants of reduced FSH and LH action that are associated with a reduced response to ovarian stimulation.
Topics: Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Luteinizing Hormone; Reproduction
PubMed: 33792685
DOI: 10.1093/humrep/deab065 -
Best Practice & Research. Clinical... Jun 2018Gonadotropins are pituitary gonadotrope-derived glycoprotein hormones. They act by binding to G-protein coupled receptors on gonads. Gonadotropins play critical roles... (Review)
Review
Gonadotropins are pituitary gonadotrope-derived glycoprotein hormones. They act by binding to G-protein coupled receptors on gonads. Gonadotropins play critical roles in reproduction by regulating both gametogenesis and steroidogenesis. Although biochemical and physiological studies provided a wealth of knowledge, gene manipulation techniques using novel mouse models gave new insights into gonadotropin synthesis, secretion and action. Both gain of function and loss of function mouse models for understanding gonadotropin action in a whole animal context have already been generated. Moreover, recent studies on gonadotropin actions in non-gonadal tissues challenged the central dogma of classical gonadotropin actions in gonads and revealed new signaling pathways in these non-gonadal tissues. In this Chapter, we have discussed our current understanding of gonadotropin synthesis, secretion and action using a variety of genetically engineered mouse models.
Topics: Animals; Follicle Stimulating Hormone; Gonadotropins; Humans; Mice; Models, Animal; Reproduction
PubMed: 29779578
DOI: 10.1016/j.beem.2018.03.006 -
International Journal of Molecular... Jun 2022The intention of this Special Edition was to collect review and original research articles that illustrate and stimulate the growing efforts to highlight the mechanisms...
The intention of this Special Edition was to collect review and original research articles that illustrate and stimulate the growing efforts to highlight the mechanisms of action of gonadotropins, as well as deepen our understanding of their biological roles in health and disease, aiming at revealing novel therapeutic opportunities in reproductive and regenerative medicine [...].
Topics: Gonadotropins; Reproduction; Virus Physiological Phenomena
PubMed: 35682981
DOI: 10.3390/ijms23116303 -
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 -
Endocrine Journal Feb 2018Several kinds of stress suppress the hypothalamic-pituitary-gonadal (HPG) axis and reproductive behavior in humans and animals. These changes can eventually cause... (Review)
Review
Several kinds of stress suppress the hypothalamic-pituitary-gonadal (HPG) axis and reproductive behavior in humans and animals. These changes can eventually cause diseases and disorders, such as amenorrhea and infertility. In previous studies, it has been shown that stress-related factors, e.g., corticotropin-releasing hormone, cortisol, and pro-inflammatory cytokines, promote the stress-induced suppression of the HPG axis. However, these mechanisms are not sufficient to explain how stress suppresses HPG axis activity, and it has been suggested that some other factors might also be involved. In the early 21st century, novel neuroendocrine peptides, kisspeptin and gonadotropin inhibitory hormone (GnIH)/RFamide-related peptide 3 (RFRP-3), which directly regulate GnRH/gonadotropin synthesis and secretion, were newly discovered. Growing evidence indicates that kisspeptin and GnIH/RFRP-3 play pivotal roles in the stress-induced disruption of the HPG axis and reproductive behavior in addition to their physiological functions. This review summarizes what is currently known about the roles of kisspeptin and GnIH/RFRP-3 in stress-induced reproductive disorders.
Topics: Animals; Gonadotropins; Humans; Infertility; Kisspeptins; Neuropeptides; Stress, Psychological
PubMed: 29375085
DOI: 10.1507/endocrj.EJ18-0026 -
Fertility and Sterility Dec 2020
Topics: Birth Rate; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropins; Humans; Ovarian Hyperstimulation Syndrome
PubMed: 33059891
DOI: 10.1016/j.fertnstert.2020.09.131 -
Andrology Nov 2014A meta-analysis was performed to systematically analyse the results of gonadotropin and GnRH therapy in inducing spermatogenesis in subjects with hypogonadotropic... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis was performed to systematically analyse the results of gonadotropin and GnRH therapy in inducing spermatogenesis in subjects with hypogonadotropic hypogonadism (HHG) and azoospermia. An extensive Medline and Embase search was performed including the following words: 'gonadotropins' or 'GnRH', 'infertility', 'hypogonadotropic', 'hypogonadism' and limited to studies in male humans. Overall, 44 and 16 studies were retrieved for gonadotropin and GnRH therapy, respectively. Of those, 43 and 16 considered the appearance of at least one spermatozoa in semen, whereas 26 and 10 considered sperm concentration upon gonadotropin and GnRH, respectively. The combination of the study results showed an overall success rate of 75% (69-81) and 75% (60-85) in achieving spermatogenesis, with a mean sperm concentration obtained of 5.92 (4.72-7.13) and 4.27 (1.80-6.74) million/mL for gonadotropin and GnRH therapy, respectively. The results upon gonadotropin were significantly worse in studies involving only subjects with a pre-pubertal onset HHG, as compared with studies involving a mixed population of pre- and post-pubertal onset [68% (58-77) vs. 84% (76-89), p = 0.011 and 3.37 (2.25-4.49) vs. 12.94 (8.00-17.88) million/mL, p < 0.0001; for dichotomous and continuous data, respectively]. A similar effect was observed also upon GnRH. No difference in terms of successful achievement of spermatogenesis and sperm concentration was found for different FSH preparations. Previous use of testosterone replacement therapy (TRT) did not affect the results obtained with gonadotropins. Finally, a higher success rate was found for subjects with lower levels of gonadotropins at the baseline and for those using both human chorionic gonadotropin and FSH. Gonadotropin therapy, even with urinary derivatives, is a suitable option in inducing/restoring fertility in azoospermic HHG subjects. Gonadotropins appear to be more efficacious in subjects with a pure secondary nature (low gonadotropins) and a post-pubertal onset of the disorder, whereas previous TRT does not affect outcome.
Topics: Female; Gonadotropins; Humans; Spermatogenesis
PubMed: 25271205
DOI: 10.1111/andr.262 -
Frontiers in Endocrinology 2021Gonadotropin-inhibitory hormone (GnIH) was first discovered in the Japanese quail, and peptides with a C-terminal LPXRFamide sequence, the signature protein structure... (Review)
Review
Gonadotropin-inhibitory hormone (GnIH) was first discovered in the Japanese quail, and peptides with a C-terminal LPXRFamide sequence, the signature protein structure defining GnIH orthologs, are well conserved across vertebrate species, including fish, reptiles, amphibians, avians, and mammals. In the mammalian brain, three RFamide-related proteins (RFRP-1, RFRP-2, RFRP-3 = GnIH) have been identified as orthologs to the avian GnIH. GnIH is found primarily in the hypothalamus of all vertebrate species, while its receptors are distributed throughout the brain including the hypothalamus and the pituitary. The primary role of GnIH as an inhibitor of gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin release is well conserved in mammalian and non-mammalian species. Circadian rhythmicity of GnIH, regulated by light and seasons, can influence reproductive activity, mating behavior, aggressive behavior, and feeding behavior. There is a potential link between circadian rhythms of GnIH, anxiety-like behavior, sleep, stress, and infertility. Therefore, in this review, we highlight the functions of GnIH in biological rhythms, social behaviors, and reproductive and non-reproductive activities across a variety of mammalian and non-mammalian vertebrate species.
Topics: Animals; Glycoproteins; Gonadotropins; Humans; Hypothalamic Hormones; Periodicity; Social Behavior
PubMed: 34566893
DOI: 10.3389/fendo.2021.728862