| 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.
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.
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]
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.
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.
