Summary: Glycoprotein hormone
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This is the Wikipedia entry entitled "Gonadotropin". More...
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Gonadotropin Edit Wikipedia article
Gonadotropins (or glycoprotein hormones) are protein hormones secreted by gonadotrope cells of the anterior pituitary of vertebrates. This is a family of proteins, which include the mammalian hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), placental chorionic gonadotropins hCG and eCG 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. The hormones LH and FSH are secreted by the anterior pituitary gland, while hCG and eCG are secreted by the placenta.
Gonadotropin is sometimes abbreviated Gn. The British spelling is gonadotrophin.
Natural types and subunit structure
The two principal gonadotropins in vertebrates are luteinizing hormone (LH) and follicle-stimulating hormone (FSH), although primates produce a third gonadotropin called chorionic gonadotropin (CG). LH and FSH are heterodimers consisting of two peptide chains, an alpha chain and a beta chain. LH and FSH share nearly identical alpha chains (about 100 amino acids long), whereas the beta chain provides specificity for receptor interactions. These subunits are heavily modified by glycosylation.
The alpha subunit is common to each protein dimer (well conserved within species, but differing between them), and a unique beta subunit, which confers biological specificity. The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulfide bonds, as shown in the following schematic representation.
+---------------------------+ +----------+| +-------------|--+ | || | | | xxxxCxCxxxxxxCxCCxxxxxxxxxxxxxCCxxxxxxxxxxCxCxxCx | | | | +------|-----------------+ | | | +----------------------------+
'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.
Gonadotropin receptors are embedded in the surface of the target cell membranes and coupled to the G-protein system. Signals triggered by binding to the receptor are relayed within the cells by the cyclic AMP second messenger system.
Gonadotropins are released under the control of gonadotropin-releasing hormone (GnRH) from the arcuate nucleus and preoptic area of the hypothalamus. The gonads — testes and ovaries — are the primary target organs for LH and FSH. The gonadotropins affect multiple cell types and elicit multiple responses from the target organs. As a simplified generalization, LH stimulates the Leydig cells of the testes and the theca cells of the ovaries to produce testosterone (and indirectly estradiol), whereas FSH stimulates the spermatogenic tissue of the testes and the granulosa cells of ovarian follicles.
Gonadotropin deficiency due to pituitary disease results in hypogonadism, which can lead to infertility. Treatment includes administered gonadotropins, which, therefore, work as fertility medication. Such can either be produced by extraction and purification from urine or be produced by recombinant DNA.
Failure or loss of the gonads usually results in elevated levels of LH and FSH in the blood.
There are various preparations of gonadotropins for therapeutic use, mainly as fertility medication. For example, the so-called menotropins (also called human menopausal gonadotropins) consist of LH and FSH extracted from human urine from menopausal women. There are also recombinant variants.
- Parhar, Ishwar S. (2002). Gonadotropin-releasing Hormone: Molecules and Receptors. Amsterdam: Elsevier. ISBN 0-444-50979-8.
- Pierce JG, Parsons TF (1981). "Glycoprotein hormones: structure and function". Annu. Rev. Biochem. 50: 465–495. doi:10.1146/annurev.bi.50.070181.002341. PMID 6267989.
- Stockell Hartree A, Renwick AG (1992). "Molecular structures of glycoprotein hormones and functions of their carbohydrate components". Biochem. J. 287 (Pt 3): 665–679. PMC 1133060. PMID 1445230.
- Goodwin RG, Moncman CL, Rottman FM, Nilson JH (1983). "Characterization and nucleotide sequence of the gene for the common alpha subunit of the bovine pituitary glycoprotein hormones". Nucleic Acids Res. 11 (19): 6873–6882. doi:10.1093/nar/11.19.6873. PMC 326420. PMID 6314263.
- Godine JE, Chin WW, Habener JF (1982). "alpha Subunit of rat pituitary glycoprotein hormones. Primary structure of the precursor determined from the nucleotide sequence of cloned cDNAs". J. Biol. Chem. 257 (14): 8368–8371. PMID 6177696.
- Golos TG, Durning M, Fisher JM (1991). "Molecular cloning of the rhesus glycoprotein hormone alpha-subunit gene". DNA Cell Biol. 10 (5): 367–380. doi:10.1089/dna.1991.10.367. PMID 1713773.
- Isaacs NW, Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ (1994). "Crystal structure of human chorionic gonadotropin". Nature 369 (6480): 455–461. doi:10.1038/369455a0. PMID 8202136.
- Menotropins at the US National Library of Medicine Medical Subject Headings (MeSH)
- Gonadotropins at the US National Library of Medicine Medical Subject Headings (MeSH)
- Gonadotropin at eMedicine Dictionary
- 10th International Symposium on GnRH
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External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000476Glycoprotein 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.
+---------------------------+ +----------+| +-------------|--+ | || | | | xxxxCxCxxxxxxCxCCxxxxxxxxxxxxxCCxxxxxxxxxxCxCxxCx | | | | +------|-----------------+ | | | +----------------------------+ '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].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extracellular region (GO:0005576)|
|Molecular function||hormone activity (GO:0005179)|
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The cytokine families in this clan have the cystine-knot fold. In this 6 cysteines form three disulphide bridges that are interlinked.
The clan contains the following 9 members:Coagulin Cys_knot DAN Hormone_6 NGF Noggin PDGF Sclerostin TGF_beta
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Number in seed:||10|
|Number in full:||201|
|Average length of the domain:||91.40 aa|
|Average identity of full alignment:||69 %|
|Average coverage of the sequence by the domain:||81.48 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hormone_6 domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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