Gonadotropin
| Glycoprotein hormone | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Hormone_6 | ||||||||
| Pfam | PF00236 | ||||||||
| InterPro | IPR000476 | ||||||||
| PROSITE | PDOC00623 | ||||||||
| SCOP2 | 1hcn /SCOPe /SUPFAM | ||||||||
| |||||||||
Gonadotropins areglycoproteinhormones secreted bygonadotropic cells of theanterior pituitary ofvertebrates.[1][2][3] They are central to the complexendocrine system that regulates normalgrowth,sexual development, andreproductive function.[4] The hormone family includes themammalian hormonesfollicle-stimulating hormone (FSH) andluteinizing hormone (LH), theplacental/chorionic gonadotropins,human chorionic gonadotropin (hCG) andequine chorionic gonadotropin (eCG),[3] as well as at least two forms offish gonadotropins. LH and FSH are secreted by the anteriorpituitary gland, while hCG and eCG are secreted by the placenta inpregnant women andmares, respectively.[5] The gonadotropins act on thegonads, controllinggamete andsex hormone production.
Gonadotropin is sometimes abbreviatedGn. The alternative spellinggonadotrophin which inaccurately implies a nourishing mechanism[6] is also used.
There are variouspreparations of gonadotropins fortherapeutic use, mainly asfertility medication. There are alsofad diet orquack preparations, which are illegal in various countries.
Natural types and subunit structure
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 twopeptide 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 forreceptor interactions. 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 theplacenta duringpregnancy.
Mechanism
Gonadotropin receptors are embedded in the surface of the targetcell membranes and coupled to theG-protein system. Signals triggered by binding to the receptor are relayed within the cells by thecyclic AMP second messenger system.
Gonadotropins are released under the control ofgonadotropin-releasing hormone (GnRH) from the arcuate nucleus and preoptic area of thehypothalamus. Thegonads —testes andovaries — 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 theLeydig cells of the testes and thetheca cells of the ovaries to producetestosterone (and indirectlyestradiol), whereas FSH stimulates the spermatogenic tissue of thetestes and thegranulosa cells ofovarian follicles, as well as stimulating production ofestrogen by the ovaries.
Although gonadotropins are secreted in apulsatile manner (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 luteum until theplacenta takes over the production of these hormones.[9]
Diseases
Gonadotropin deficiency due topituitary disease 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 hypoplasia in males, andFSH insensitivity, are conditions of insensitivity to LH and FSH, respectively, caused byloss-of-function mutations in their respective signaling receptors. Another closely related condition to these isGnRH insensitivity.
Pharmaceutical preparations
There are variouspreparations of gonadotropins fortherapeutic use, mainly asfertility medication. For example, the so-calledmenotropins (also calledhuman menopausal gonadotropins) consist of LH and FSH extracted from theurine ofmenopausal women.[12] There are alsorecombinant variants. Besides the aforementioned legitimatepharmaceutical drugs, there arefad diet orquack preparations, which are illegal in various countries.
See also
References
- ^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".Annual Review of Biochemistry.50:465–95.doi:10.1146/annurev.bi.50.070181.002341.PMID 6267989.
- ^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.PMC 1133060.PMID 1445230.
- ^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.PMID 6177696.
- ^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.PMID 1713773.
- ^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.PMID 13917136.S2CID 9747521.
- ^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.PMC 326420.PMID 6314263.
- ^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.PMID 8202136.S2CID 4263358.
- ^Laurence A. Cole (21 September 2010).Human Chorionic Gonadotropin (hCG). Elsevier. pp. 205–.ISBN 978-0-12-384908-3.
- ^Basaria S (April 2014). "Male hypogonadism".Lancet.383 (9924):1250–63.doi:10.1016/S0140-6736(13)61126-5.PMID 24119423.S2CID 30479724.
- ^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.PMID 18404388.S2CID 6666672.
- ^Menotropins at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
External links
- Gonadotropins at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
- 10th International Symposium on GnRH
