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27-496: Gonadotropin is sometimes abbreviated Gn . The alternative spelling gonadotrophin which inaccurately implies a nourishing mechanism is also used. There are various preparations of gonadotropins for therapeutic use, mainly as fertility medication . There are also fad diet or quack preparations, which are illegal in various countries. The two principal gonadotropins in vertebrates are luteinizing hormone (LH) and follicle-stimulating hormone (FSH), although primates produce

54-711: A gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones . The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia ), hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics , resulting in sexual infantilism if left untreated), and infertility . Leydig cell hypoplasia does not occur in people with XX chromosomes as they do not have either Leydig cells or testicles. However,

81-420: A pulsatile manner (as a result of pulsatile GnRH release), unlike the case of GnRH and GnRH 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

108-525: A female gender identity or gender variance , hypergonadotropic hypogonadism ( hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent puberty with an associated reduction in or complete lack of development of secondary sexual characteristics ( sexual infantilism ), impaired fertility or complete sterility , tall stature (due to delayed epiphyseal closure ), eunuchoid skeletal proportions, delayed or absent bone maturation , and osteoporosis . Leydig cell hypoplasia

135-434: A lower pregnancy rate, but with significantly higher estradiol (E2) levels. The package insert for Puregon states that structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (hFSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural hFSH. However, these small differences do not affect

162-480: 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

189-441: A unique beta subunit 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. '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

216-661: Is caused by genetic mutations in LHCGR , a gene which encodes the LH/hCG receptor . LH normally acts through the LH/hCG receptor to stimulate the growth of Leydig cells in the testicles and the production of androgens such as testosterone and dihydrotestosterone (DHT) by these cells. In Leydig cell hypoplasia however, there is a reduced capacity for the LH/hCG receptor to respond to LH. This results in hypoplasia or absence of Leydig cells, testicular atrophy , and lower than normal androgen levels. In

243-455: Is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated. Another human gonadotropin is human chorionic gonadotropin (hCG), produced by the placenta during pregnancy . Gonadotropin receptors are embedded in the surface of the target cell membranes and coupled to the G-protein system. Signals triggered by binding to

270-441: Is usually administered between ages 4 and 9. Derived from the urine of pregnant women. Leydig cell hypoplasia Leydig cell hypoplasia (or aplasia ) ( LCH ), also known as Leydig cell agenesis , is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 individuals with XY chromosomes. It is characterized by an inability of the body to respond to luteinizing hormone (LH),

297-423: The corpus luteum until the placenta takes over the production of these hormones. 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

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324-796: The bioactivity compared to natural hFSH. Gonal-f was approved for medical use in the European Union in October 1995. Puregon was approved for medical use in the European Union in February 1996. Rekovelle was approved for medical use in the European Union in December 2016. Ovaleap was approved for medical use in the European Union in September 2013. It was approved for medical use in Australia in March 2021. Bemfola

351-508: The cause of the condition in people with XY chromosomes, luteinizing hormone insensitivity , does affect people with XX chromosomes, and because LH plays a role in the female reproductive system , it can result in primary amenorrhea or oligomenorrhea (absent or reduced menstruation ), infertility due to anovulation , and ovarian cysts . A related condition is follicle-stimulating hormone (FSH) insensitivity , which presents with similar symptoms to those of Leydig cell hypoplasia but with

378-461: The diagnosis is confirmed on biopsy of the testes, revealing either absent or hypoplastic Leydig cells . The inside of the testis will be grayish and mucous, displaying arrested spermatogenesis and the presence of Sertoli cells. The diagnosis can also be confirmed by looking for mutations in the gene for the LH receptor. A diagnosis of Leydig cell hypoplasia is usually made in the neonatal period, following

405-479: The discovery of ambiguous genitalia, or at puberty, when secondary sex characteristics fail to develop. Puberty is the most common time for Leydig cell hypoplasia to be diagnosed. Patients with Leydig cell hypoplasia may be treated with hormone replacement therapy (i.e., with androgens), which will result in normal sexual development and the resolution of most symptoms. In the case of 46,XY (genetically "male") individuals who are phenotypically female and/or have

432-551: The gonads usually results in elevated levels of LH and FSH in the blood. LH insensitivity , which results in Leydig cell hypoplasia in males, and FSH insensitivity , are conditions of insensitivity to LH and FSH, respectively, caused by loss-of-function mutations in their respective signaling receptors. Another closely related condition to these is GnRH insensitivity . There are various preparations of gonadotropins for therapeutic use, mainly as fertility medication . For example,

459-543: The most severe form of the condition in which there is a complete lack of response of the Leydig cells to LH, androgen production by the testicles is virtually negligible and secondary sexual characteristics entirely fail to develop at puberty . Since the Sertoli cells are not affected by Leydig cell hypoplasia, anti-Müllerian hormone is secreted normally and so there are no Müllerian structures . Wolffian structures , such as

486-701: The physiological effects of gonadotropins , used therapeutically mainly as fertility medication for ovarian hyperstimulation and ovulation induction . For example, the so-called menotropins consist of LH and FSH extracted from human urine from menopausal women. There are also recombinant variants. hMG (human Menopausal Gonadotrophins), FSH and LH prepared from human urine collected from postmenopausal women. First extracted in 1953. Injected intra-muscularily (IM) or subcutaneously (SC). Generic Brands Common side effects of preparations containing FSH and LH are: Preparations of follicle-stimulating hormone (FSH) mainly include those derived from

513-466: The prostate, vasa deferentia, and epidydimides are present. In type I, abdominal testes are revealed on ultrasound; in type II testes may be descended or undescended. People with Leydig cell hypoplasia type I display no response to the hCG stimulation test; there is no increase in serum levels of testosterone and dihydrotestosterone . Leydig cell hypoplasia type II can display either a pronounced rise of testosterone levels or no rise. In any case,

540-408: 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

567-403: The recombinant preparation Follistim. The package insert for Gonal-f states that based on physio-chemical tests and bioassays that follitropin beta and follitropin alfa are indistinguishable. Two studies showed no difference. However, a more recent study showed there may be a slight clinical difference, with the alfa form tending towards a higher pregnancy rate and the beta form tending towards

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594-422: The so-called menotropins (also called human menopausal gonadotropins ) consist of LH and FSH extracted from the urine of menopausal women. There are also recombinant variants. Besides the aforementioned legitimate pharmaceutical drugs , there are fad diet or quack preparations, which are illegal in various countries. Gonadotropin preparations Gonadotropin preparations are drugs that mimic

621-614: The symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in XX individuals and difficulties with fertility in XY individuals). Despite their similar causes, FSH insensitivity is considerably less common in comparison to LH insensitivity. The symptoms of Leydig cell hypoplasia include pseudohermaphroditism, i.e., feminized , ambiguous , or relatively mildly underdeveloped (e.g., micropenis , severe hypospadias , and/or cryptorchidism [undescended testes]) external genitalia ,

648-409: 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 , as well as stimulating production of estrogen by the ovaries. Although gonadotropins are secreted in

675-462: The urine of menopausal women, as well as recombinant preparations. The recombinant preparations are more pure and more easily administered, but they are more expensive. The urinary preparations are equally effective and less expensive, but are not as convenient to administer as they are available in vials versus injection pens. One study reported that users of the purified urinary FSH preparation Bravelle experienced less injection site pain compared to

702-813: The urine of pregnant women or be produced from recombinant DNA. It acts similarly to LH, but the larger supply makes it less costly; it also has a longer half-life. In veterinary medicine , equine chorionic gonadotropin (eCG) extracted from pregnant mare serum is used instead on a variety of mammals, sometimes eliciting an immune response in non-horse species. In Women: Used to induce final maturation of follicle and subsequent ovulation. Also used for luteal phase support. In men: Used to treat select cases of Hypogonadotropic Hypogonadism in adult males. In off-label use, some urologists prescribe hCG in low doses in combination with testosterone replacement to preserve fertility. In male children: Also used to treat prepubertal cryptorchidism not due to anatomical obstruction. Therapy

729-689: Was approved for medical use in the European Union in March 2014. Side effects of FSH preparations include: Corifollitropin alfa Merck received approval on February 15, 2010, from the European Commission for ELONVA (corifollitropin alfa) a long lasting single injection fusion protein lacking LH activity. Only one injection is required for the first seven days, replacing the first seven daily injections of conventional FSH. Initial results demonstrates similar pregnancy rates as daily recombinant FSH injections. Prepared from recombinant DNA. Human chorionic gonadotropin (hCG) can be recovered from

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