Gonadotropin
| Glycoprotein hormone | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Hormone_6 | ||||||||
| Pfam | PF00236 | ||||||||
| InterPro | IPR000476 | ||||||||
| PROSITE | PDOC00623 | ||||||||
| SCOP2 | 1hcn/SCOPe/SUPFAM | ||||||||
| |||||||||
Gonadotropinsareglycoproteinhormonessecreted bygonadotropic cellsof theanterior pituitaryofvertebrates.[1][2][3]This family includes themammalianhormonesfollicle-stimulating hormone(FSH) andluteinizing hormone(LH), theplacental/chorionicgonadotropins,human chorionic gonadotropin(hCG) andequine chorionic gonadotropin(eCG),[3]as well as at least two forms offishgonadotropins. These hormones are central to the complexendocrine systemthat regulates normalgrowth,sexual development,andreproductive function.[4]LH and FSH are secreted by the anteriorpituitary gland,while hCG and eCG are secreted by the placenta inpregnanthumans andmares,respectively.[5]The gonadotropins act on thegonads,controllinggameteandsex hormoneproduction.
Gonadotropin is sometimes abbreviatedGn.The alternative spellinggonadotrophinwhich inaccurately implies a nourishing mechanism[6]is also used.
There are variouspreparations of gonadotropinsfortherapeuticuse, mainly asfertility medication.There are alsofad dietorquackpreparations, which are illegal in various countries.
Natural types and subunit structure[edit]
The two principal gonadotropins in vertebrates areluteinizing hormone(LH) andfollicle-stimulating hormone(FSH), although primates produce a third gonadotropin calledchorionic gonadotropin(CG). LH and FSH are heterodimers consisting of twopeptidechains,an alpha chainand a beta chain. LH and FSH share nearly identical alpha chains (about 100 amino acids long), whereas the beta chain provides specificity forreceptorinteractions. These subunits are heavily modified byglycosylation.
The alpha subunit is common to each protein dimer (well conserved within species, but differing between them),[4]and a unique beta subunit confers biological specificity.[7]The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulfide bonds,[8]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.[7]
Another human gonadotropin ishuman chorionic gonadotropin(hCG), produced by theplacentaduringpregnancy.
Mechanism[edit]
Gonadotropin receptorsare embedded in the surface of the targetcell membranesand coupled to theG-proteinsystem. Signals triggered by binding to the receptor are relayed within the cells by thecyclic AMPsecond messenger system.
Gonadotropins are released under the control ofgonadotropin-releasing hormone(GnRH) from the arcuate nucleus and preoptic area of thehypothalamus.Thegonads—testesandovaries— 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 theLeydigcells of the testes and thetheca cellsof the ovaries to producetestosterone(and indirectlyestradiol), whereas FSH stimulates the spermatogenic tissue of thetestesand thegranulosa cellsofovarian follicles,as well as stimulating production ofestrogenby the ovaries.
Although gonadotropins are secreted in apulsatilemanner (as a result of pulsatile GnRH release), unlike the case of GnRH andGnRH agonists,constant/non-pulsatile activation of the gonadotropin receptors by the gonadotropins does not produce functional inhibition. This can be seen during the first 7–10 weeks of pregnancy, where constantly high and progressively-increasing levels of hCG circulate and mediate production of estrogen and progesterone by thecorpus luteumuntil theplacentatakes over the production of these hormones.[9]
Diseases[edit]
Gonadotropin deficiency due topituitarydisease results inhypogonadism,which can lead toinfertility.Treatment includes administered gonadotropins, which, therefore, work asfertility medication.Such can either be produced by extraction and purification from urine or be produced byrecombinant DNA.
Failure or loss of the gonads usually results in elevated levels of LH and FSH in the blood.[10][11]
LH insensitivity,which results inLeydig cell hypoplasiain males, andFSH insensitivity,are conditions of insensitivity to LH and FSH, respectively, caused byloss-of-function mutationsin their respective signaling receptors. Another closely related condition to these isGnRH insensitivity.
Pharmaceutical preparations[edit]
There are variouspreparations of gonadotropinsfortherapeuticuse, mainly asfertility medication.For example, the so-calledmenotropins(also calledhuman menopausal gonadotropins) consist of LH and FSH extracted from theurineofmenopausalwomen.[12]There are alsorecombinantvariants. Besides the aforementioned legitimatepharmaceutical drugs,there arefad dietorquackpreparations, which are illegal in various countries.
See also[edit]
References[edit]
- ^Parhar, Ishwar S. (2002).Gonadotropin-releasing Hormone: Molecules and Receptors.Amsterdam: Elsevier.ISBN0-444-50979-8.
- ^Pierce JG, Parsons TF (1981). "Glycoprotein hormones: structure and function".Annual Review of Biochemistry.50:465–95.doi:10.1146/annurev.bi.50.070181.002341.PMID6267989.
- ^abStockell Hartree A, Renwick AG (November 1992)."Molecular structures of glycoprotein hormones and functions of their carbohydrate components".The Biochemical Journal.287 ( Pt 3) (Pt 3): 665–79.doi:10.1042/bj2870665.PMC1133060.PMID1445230.
- ^abGodine JE, Chin WW, Habener JF (July 1982)."alpha Subunit of rat pituitary glycoprotein hormones. Primary structure of the precursor determined from the nucleotide sequence of cloned cDNAs".The Journal of Biological Chemistry.257(14): 8368–71.doi:10.1016/S0021-9258(18)34340-0.PMID6177696.
- ^Golos TG, Durning M, Fisher JM (June 1991). "Molecular cloning of the rhesus glycoprotein hormone alpha-subunit gene".DNA and Cell Biology.10(5): 367–80.doi:10.1089/dna.1991.10.367.PMID1713773.
- ^Stewart J, Li CH (August 1962). "On the use of -tropin or -trophin in connection with anterior pituitary hormones".Science.137(3527): 336–7.Bibcode:1962Sci...137..336S.doi:10.1126/science.137.3527.336.PMID13917136.S2CID9747521.
- ^abGoodwin RG, Moncman CL, Rottman FM, Nilson JH (October 1983)."Characterization and nucleotide sequence of the gene for the common alpha subunit of the bovine pituitary glycoprotein hormones".Nucleic Acids Research.11(19): 6873–82.doi:10.1093/nar/11.19.6873.PMC326420.PMID6314263.
- ^Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, et al. (June 1994). "Crystal structure of human chorionic gonadotropin".Nature.369(6480): 455–61.Bibcode:1994Natur.369..455L.doi:10.1038/369455a0.PMID8202136.S2CID4263358.
- ^Laurence A. Cole (21 September 2010).Human Chorionic Gonadotropin (hCG).Elsevier. pp. 205–.ISBN978-0-12-384908-3.
- ^Basaria S (April 2014). "Male hypogonadism".Lancet.383(9924): 1250–63.doi:10.1016/S0140-6736(13)61126-5.PMID24119423.S2CID30479724.
- ^Rothman MS, Wierman ME (2008). "Female hypogonadism: evaluation of the hypothalamic-pituitary-ovarian axis".Pituitary.11(2): 163–9.doi:10.1007/s11102-008-0109-3.PMID18404388.S2CID6666672.
- ^Menotropinsat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
External links[edit]
- Gonadotropinsat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
- 10th International Symposium on GnRH
