This book systematically introduces the basic knowledge of the Hypothalamic Pituitary Gonads (HPG) axis and provides information on the location and regulation, gene mutations, function, reproduction, life cycle, sexual behaviour, disorders and the role of the environmental factors on GnRH gene. Also, we focused on gene and receptor structures, and the signalling pathways of GnRH, and its related genes and hormones such as Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Progesterone (P4) and Oestradiol (E2). Also, it was pointed to Gonadotropin Inhibiting Hormone (GnIH) and its related peptides, such as RFamide peptides which were found to decrease hormones secretion by working on HPG in an inhibiting biosynthesis process of gonadotropin (α–β) subunits. In addition, the roles of hormones on fertility and reproduction, also, disruption resulted from mutations. Special characteristics of many hormones and pulsatile secretions of GnRH were summarized.
This information is necessary for an understanding way of work some necessary hormones also, elucidating reasons infertility. Although, several studies have presented a lot of kinds of regulators of expression for many genes related by fertility in many species, however, the knowledge of the relationship between molecular relating and infertility still has many gaps and problematic, also, many remains to be discovered, and a lot of significant questions (such as sexual behaviour, the regulation of gonadotropin secretion, and growth of tumour cell, in addition to; whether GnRHs are expressed as a full-length or not?), need to be solved, and mechanisms of pulsatile secretions and potential functions of many reproductive hormones need to be elucidated. So, this investigation very important for those researchers and readers to start solve and answer these questions and understanding many things related to (HPG) axis, and (GnRH).
Table of Contents
1. INTRODUCTION
2. GONADOTROPIN-RELEASING HORMONE (GnRH)
2.1. Gonadotropin-releasing hormone (GnRH) signalling pathway
2.2. Gonadotropin-Releasing Hormone gene (GnRH gene)
2.3. Gonadotropin-Releasing Hormone Receptor (GnRH-R)
2.4. GnRH peptides and receptors
2.5. GnRH gene Transcription Regulation
2.5.1. Oct-1, Oct-2, Pit-1and Unc86
2.5.2. Dlx-2 and Msx-1
2.5.3. Pbx-1
2.5.4. Homeobox protein (Otx-2)
2.5.5. GATA-A and GATA-B
2.5.6. PKC, Jun, Fos, AP-1, and NK-B
2.5.7. Pur-A, Pur-B, Brn-2, hnRNP-A/B, and hnRNP-G
2.5.8. Kisspeptin
2.6. Expression of the GnRH-R gene
2.7. Effects of GnRH activation of GnRH-R and its signalling pathways
3. GONADOTROPINS (Gn)
3.1. Luteinizing hormone (LH)
3.1.1. Regulation of LH (LH-β) by GnRH
3.1.2. Regulation of LH-β by Follistatin (Fo), Activin (Ac), and Inhibin (In)
3.1.3. Regulation of LH-β by Estrogen (E) and Androgen (An)
3.2. Follicle-Stimulating Hormone (FSH)
3.2.1. Regulation of FSH (FSH-β) by GnRH
3.2.2. Transcriptional regulation of FSH-β encoding genes
4. PROGESTERONE (P4) AND OESTRADIOL (E2)
5. SUMMARY POINTS LIST
6. CHALLENGES AND FUTURE DIRECTIONS
7. LITERATURE CITED
7.1. RELATED RESOURCES
Objectives and Core Topics
The primary objective of this work is to provide a comprehensive scientific summary of the regulatory actions of Gonadotropin-Releasing Hormone (GnRH) as both a gene and a hormone, while examining its specific endocrine receptors and signalling pathways across various species, including humans, cattle, sheep, and pigs.
- Molecular regulation and signalling pathways of the Hypothalamic-Pituitary-Gonadal (HPG) axis.
- Transcriptional regulation of the GnRH gene, including the role of transcription factors and co-repressors.
- Mechanism of action for gonadotropins like LH and FSH and their subunit regulation.
- Impact of steroid hormones (Progesterone and Oestradiol) on GnRH receptor expression and reproductive feedback loops.
Excerpt from the Book
1. INTRODUCTION
The Hypothalamic Pituitary Gonadal axis (HPG) plays important roles in steroids production, body development, reproductive activities and ageing in male and female. They also participate in the regulation of a number of the body systems, such as the immune and reproductive systems (66). Therefore, controlling the release of some important hormones like; Gonadotropin-Releasing Hormone (GnRH), Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), testosterone and Estrogen (E) either directly or indirectly should be beneficial to several biological body activities (136; 199). GnRH is secreted from the hypothalamus through GnRH-expressing neurons. Thus, the anterior portion of the pituitary gland produces two basic hormones LH and FSH, then successively the gonads are stimulated to produce sex hormones, testosterone in males and estrogen in females (15).
The HPG axis consists of 3 levels: hypothalamus, pituitary, and gonads (ovaries in females and testes in the males). GnRH, LH and FSH together with sex hormones are all products of HPG axis. Moreover, differentiation and maturation of reproductive organs, steroids excretions, spermatogenesis in mature males and oogenesis in mature females are all mediated via several reproductive hormones controlled by HPG, Figure (1) (66).
Chapter Summaries
1. INTRODUCTION: Provides an overview of the Hypothalamic-Pituitary-Gonadal (HPG) axis, its role in reproductive function, and the discovery of RFamide-related peptides (RFRPs).
2. GONADOTROPIN-RELEASING HORMONE (GnRH): Details the signalling pathways, gene structure, and complex transcriptional regulation of GnRH, including the roles of specific transcription factors like Oct-1 and Kisspeptin.
3. GONADOTROPINS (Gn): Discusses the function and regulation of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), focusing on their transcriptional control by various hormones and signalling pathways.
4. PROGESTERONE (P4) AND OESTRADIOL (E2): Explores the feedback mechanisms of ovarian steroids on the pituitary gland and their specific effects on GnRH receptor mRNA expression.
5. SUMMARY POINTS LIST: Recaps key findings regarding the molecular pathways and genetic factors influencing the HPG axis and fertility.
6. CHALLENGES AND FUTURE DIRECTIONS: Outlines the remaining gaps in research, particularly regarding the molecular mechanisms of GnRH gene transcription and receptor regulation in various species.
7. LITERATURE CITED: A comprehensive bibliography of referenced scientific research supporting the discussed concepts.
Keywords
HPG, GnRH, GnRHR, Gonadotropins, LH, FSH, Kisspeptin, Gene Transcription, Signalling Pathways, Reproductive Hormones, Steroid Feedback, Hypothalamus, Pituitary, Fertility, Endocrine Receptors
Frequently Asked Questions
What is the core focus of this publication?
The work focuses on the molecular regulation of the Hypothalamic-Pituitary-Gonadal (HPG) axis, detailing how genes and hormones interact to govern reproductive processes.
Which hormonal systems are central to this work?
The study centers on GnRH, its receptors (GnRH-R), gonadotropins (LH and FSH), and steroid hormones like Progesterone and Oestradiol.
What is the primary research goal?
The primary goal is to present a comprehensive summary of GnRH regulation at the gene and hormone level, and to elucidate the molecular signalling pathways in both male and female mammals.
Which scientific methods are primarily discussed?
The text reviews various molecular approaches, including genetic mapping, promoter analysis (e.g., in GT1-7 cells), gene knock-out studies, and transcriptomic pathway analysis.
What is covered in the main body of the work?
The main body provides deep insights into GnRH gene structure, transcriptional regulation via factors like Oct-1 and GATA, GnRH receptor signalling, and the hormonal feedback loops influencing gonadotropin secretion.
What are the key descriptive keywords for this study?
Key terms include HPG axis, GnRH, GnRHR, Gonadotropins, LH, FSH, Kisspeptin, and reproductive feedback mechanisms.
How does GnRH signalling affect gene expression in pituitary cells?
GnRH binding to its receptor triggers multiple pathways, including the MAPK/ERK and Protein Kinase C pathways, which coordinate the expression of LH and FSH subunits.
What role does Kisspeptin play in this axis?
Kisspeptin is a critical neuropeptide that acts as a central regulator of GnRH pulse generation and GnRH gene expression, essential for puberty and reproductive physiology.
Why is the C-terminal tail of the GnRH receptor significant?
The C-terminal tail is often crucial for receptor internalization and desensitization, with significant structural differences existing between GnRH-RI and GnRH-RII in various species.
- Quote paper
- Ahmed Saleh (Author), Amr Rashadb (Author), Nada Hassaninea (Author), Yongju Zhaoa (Author), Mahmoud Sharabyb (Author), 2020, Genetics Basis of Gonadotropin-Releasing Hormone GnRH, Munich, GRIN Verlag, https://www.grin.com/document/512579
