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Gonadotropin-Releasing Hormone Receptor Signaling and Functions 2.0
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Gonadotropin-Releasing Hormone Receptor Signaling and Functions 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 13122

Special Issue Editor

Prof. Dr. Zvi Naor

E-Mail Website
Guest Editor
Department of Biochemistry and Neurobiology, Tel Aviv University, Ramat Aviv 69978, Israel
Interests: signal transduction; GnRH receptor; gonadotropins; pituitary; gonadotropes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue “Gonadotropin-Releasing Hormone Receptor Signaling and Functions”.

GnRH is the primary hormone which controls the reproductive system in all vertebrates. GnRH binds to its cognate receptor (GnRHR) in pituitary gonadotropes to regulate the synthesis and secretion of the gonadotropins: Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH). LH and FSH in turn control gametogenesis and sex hormone production in the gonads. GnRHR signaling is complex and involves interactions with G-proteins: in particular Gq, elevation of cytosolic Ca2+, and activation of selective Protein Kinase C (PKC) isoforms followed by activation of Mitogen activated protein kinase (MAPK) members such as ERK1/2, JNK and p38, culminating in gonadotropin secretion and synthesis. Identification of GnRHR signaling networks is a great challenge in the field. GnRHRs are present not only in pituitary gonadotropes, but also in some sex-hormone dependent cancers, including prostate cancer. Prostate cancer, which is also known as carcinoma of the prostate (CaP), is the second highest death-causing cancer in the western world. While GnRH secretion in a pulsatile manner regulates normal reproductive functions, application of GnRH agonists (GnRH-A), or antagonists in a continuous manner, disrupts this regulation. As a result, the continuous application of GnRH-A causes desensitization of the GnRHR in the pituitary, and termination of production and secretion of LH and FSH which in turn causes reduction in testosterone secretion, known as "Chemical Castration." This is the basis for the clinical use of GnRH analogs in prostate cancer. However, in later stages, CaP may become hormone-independent, therefore, treatment with GnRH-A in a continuous manner is not beneficial for these cancers. Hence, a novel potential treatment for hormone-independent CaP is required. Indeed, direct apoptotic effects of GnRH-A upon hormone-independent CaP cells (DU-145) has been described, but the magnitude of the effect was not sufficient. Since there is no cure to advanced hormone resistant CaP, new vistas for the development of a therapy is required.

Prof. Zvi Naor
Guest Editor

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Keywords

  • Gonadotropin Releasing Hormone (GnRH)
  • GnRH Receptor
  • Pituitary cells
  • Gonadotropes
  • Prostate cancer
  • G proteins interactions

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Published Papers (3 papers)

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Review

14 pages, 563 KiB  
Review
Sex Hormones and Their Effects on Ocular Disorders and Pathophysiology: Current Aspects and Our Experience
by Raffaele Nuzzi and Paolo Caselgrandi
Int. J. Mol. Sci. 2022, 23(6), 3269; https://doi.org/10.3390/ijms23063269 - 17 Mar 2022
Cited by 31 | Viewed by 6674
Abstract
Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various [...] Read more.
Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various systems of the body. The evidence that many eye diseases differ in terms of prevalence between men and women has allowed us, in recent years, to carry out several studies that have investigated the association between sex hormones and the pathophysiology of eye tissues. Specific receptors for sex hormones have been found on the lacrimal and meibomian glands, conjunctiva, cornea, lens, retina, and choroid. This work summarizes the current knowledge on the role that sex hormones play in the pathogenesis of the most common ocular disorders and indicates our clinical experience in these situations. The aim is to stimulate an interdisciplinary approach between endocrinology, neurology, molecular biology, and ophthalmology to improve the management of these diseases and to lay the foundations for new therapeutic strategies. Full article
(This article belongs to the Special Issue Gonadotropin-Releasing Hormone Receptor Signaling and Functions 2.0)
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11 pages, 696 KiB  
Review
GnRH-Related Neurohormones in the Fruit Fly Drosophila melanogaster
by David Ben-Menahem
Int. J. Mol. Sci. 2021, 22(9), 5035; https://doi.org/10.3390/ijms22095035 - 10 May 2021
Cited by 8 | Viewed by 2978
Abstract
Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate’s decapeptide gonadotropin-releasing hormone (GnRH) and the GnRH receptor genes. Upon the characterization of these gene products, encoding peptides and putative receptors, GnRH-related peptides [...] Read more.
Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate’s decapeptide gonadotropin-releasing hormone (GnRH) and the GnRH receptor genes. Upon the characterization of these gene products, encoding peptides and putative receptors, GnRH-related peptides and their G-protein coupled receptors have been identified. These include the adipokinetic hormone (AKH) and corazonin (CRZ) in insects and their cognate receptors that pair to form bioactive signaling systems, which network with additional neurotransmitters/hormones (e.g., octopamine and ecdysone). Multiple studies in the past 30 years have identified many aspects of the biology of these peptides that are similar in size to GnRH and function as neurohormones. This review briefly describes the main activities of these two neurohormones and their receptors in the fruit fly Drosophila melanogaster. The similarities and differences between Drosophila AKH/CRZ and mammalian GnRH signaling systems are discussed. Of note, while GnRH has a key role in reproduction, AKH and CRZ show pleiotropic activities in the adult fly, primarily in metabolism and stress responses. From a protein evolution standpoint, the GnRH/AKH/CRZ family nicely demonstrates the developmental process of neuropeptide signaling systems emerging from a putative common ancestor and leading to divergent activities in distal phyla. Full article
(This article belongs to the Special Issue Gonadotropin-Releasing Hormone Receptor Signaling and Functions 2.0)
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12 pages, 794 KiB  
Review
Post-Transcriptional Regulation of Gnrhr: A Checkpoint for Metabolic Control of Female Reproduction
by Angela K. Odle, Melanie C. MacNicol, Gwen V. Childs and Angus M. MacNicol
Int. J. Mol. Sci. 2021, 22(7), 3312; https://doi.org/10.3390/ijms22073312 - 24 Mar 2021
Cited by 4 | Viewed by 2844
Abstract
The proper expression of gonadotropin-releasing hormone receptors (GnRHRs) by pituitary gonadotropes is critical for maintaining maximum reproductive capacity. GnRH receptor expression must be tightly regulated in order to maintain the normal pattern of expression through the estrous cycle in rodents, which is believed [...] Read more.
The proper expression of gonadotropin-releasing hormone receptors (GnRHRs) by pituitary gonadotropes is critical for maintaining maximum reproductive capacity. GnRH receptor expression must be tightly regulated in order to maintain the normal pattern of expression through the estrous cycle in rodents, which is believed to be important for interpreting the finely tuned pulses of GnRH from the hypothalamus. Much work has shown that Gnrhr expression is heavily regulated at the level of transcription. However, researchers have also discovered that Gnrhr is regulated post-transcriptionally. This review will discuss how RNA-binding proteins and microRNAs may play critical roles in the regulation of GnRHR expression. We will also discuss how these post-transcriptional regulators may themselves be affected by metabolic cues, specifically with regards to the adipokine leptin. All together, we present evidence that Gnrhr is regulated post-transcriptionally, and that this concept must be further explored in order to fully understand the complex nature of this receptor. Full article
(This article belongs to the Special Issue Gonadotropin-Releasing Hormone Receptor Signaling and Functions 2.0)
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