Glycoprotein hormones [ (PUBMED:6267989) (PUBMED:1445230) ] (or gonadotropins) are a family of proteins, which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin (TSH) placental chorionic gonadotropins hCG and eCG [ (PUBMED:6314263) ] and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function [ (PUBMED:6177696) ]. The hormones LH, FSH and TSH are secreted by the anterior pituitary gland, while hCG and eCG are secreted by the placenta [ (PUBMED:1713773) ]. All these hormones consist of two glycosylated chains (alpha and beta). The alpha subunit is common to each protein dimer (well conserved within species, but differing between them [ (PUBMED:6177696) ]), and a unique beta subunit, which confers biological specificity [ (PUBMED:6314263) ]. The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulphide bonds [ (PUBMED:8202136) ], as shown in the following schematic representation.
'C': conserved cysteine involved in a disulphide bond.
Intracellular levels of free alpha subunits are greater than those of the mature glycoprotein, implying that hormone assembly is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated [ (PUBMED:6314263) ].
Crystal structure of human chorionic gonadotropin.
Nature. 1994; 369: 455-61
Display abstract
The three-dimensional structure of human chorionic gonadotropin shows that each of its two different subunits has a similar topology, with three disulphide bonds forming a cystine knot. This same folding motif is found in some protein growth factors. The heterodimer is stabilized by a segment of the beta-subunit which wraps around the alpha-subunit and is covalently linked like a seat belt by the disulphide Cys 26-Cys 110. This extraordinary feature appears to be essential not only for the association of these heterodimers but also for receptor binding by the glycoprotein hormones.
Structure--function relationships of the glycoprotein hormones and their receptors.
Trends Pharmacol Sci. 1991; 12: 199-203
Display abstract
The primary structures of the glycoprotein hormones follitropin (FSH), lutropin (LH), human choriogonadotropin (hCG) and thyrotropin (TSH) have been determined, hCG has been crystallized and initial diffraction data obtained. Studies with synthetic peptides have provided information on regions involved in receptor interaction and signal transduction. The receptors for the glycoprotein hormones have been prepared by gene cloning methods and their primary structures deduced. As Leo Reichert and colleagues discuss here, although cAMP is involved in glycoprotein hormone signal transduction, recent evidence also implicates other second messengers, especially Ca2+ and may include both the phosphatidylinositol pathway and activation of Ca2+ channels.
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GHA domain which could be assigned to a KEGG orthologous group, and not all proteins containing GHA domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
