Biased signaling by human follicle-stimulating hormone variants
Alfredo Ulloa-Aguirre1, Teresa Zariñán2, James A Dias3
1Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico..
Pharmacology & Therapeutics
|February 17, 2025
Summary
Follicle-stimulating hormone (FSH) oligosaccharides critically influence its function. Variations in FSH glycosylation impact its biological activity, receptor binding, and gene regulation, leading to functional selectivity.
Area of Science:
- Endocrinology
- Reproductive Biology
- Glycobiology
Background:
- Follicle-stimulating hormone (FSH) is a crucial gonadotropin for mammalian reproduction, produced by the anterior pituitary.
- FSH targets ovarian granulosa cells and testicular Sertoli cells, regulating key reproductive functions.
- FSH structure involves alpha and beta subunits with complex, heterogeneous oligosaccharide chains.
Purpose of the Study:
- To review the impact of FSH oligosaccharide structures on hormone function.
- To explore how variations in FSH glycosylation lead to functional selectivity.
- To highlight the role of carbohydrate heterogeneity in FSH's biological activity.
Main Methods:
- Review of in vitro and in vivo studies on FSH glycosylation.
- Analysis of the effects of carbohydrate variations on FSH's physiological and biological features.
- Examination of FSH's interaction with its cognate receptor and downstream signaling.
Main Results:
- Oligosaccharide structures are essential for FSH subunit assembly, stability, secretion, and half-life.
- Carbohydrate heterogeneity (micro- and macroheterogeneity) significantly affects FSH's biological activity.
- Variations in FSH glycosylation influence circulatory survival, receptor binding, signaling, and gene regulation.
Conclusions:
- FSH glycosylation is a key determinant of its functional selectivity.
- Understanding FSH oligosaccharide variations is crucial for comprehending its diverse physiological roles.
- Targeting FSH glycosylation may offer novel therapeutic strategies in reproductive medicine.
Related Concept Videos
01:06Multipotency and Niche of Bulge Stem Cell
3.4K
A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
3.4K
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
03:14Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
01:19Regulation of Hormone Secretion
3.1K
Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral...
Humoral...
3.1K
01:22Target Cell Response to Hormones
2.8K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
2.8K
01:08Chemical Signaling in the Endocrine System
3.0K
A signaling cascade is a series of events that facilitates the transmission of information within or between cells, culminating in a targeted response in the recipient cell. As chemical messengers, hormones are pivotal in initiating and modulating these intricate signaling cascades based on their solubility.
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...
3.0K