Gonadotropin-releasing hormone (GnRH): features, preparations and analogues

Gonadotropin-releasing hormone (GnRH) is known as a hormone that releases the luteinizing hormone (LHRH) and lylyberyrin, which is a peptide trophic hormone and is responsible for the release of the luteinizing hormone from the adenohypophysis (LH) and follicle stimulating hormone (LH). GnRH is a hormone synthesized and released in the hypothalamus from GnRH neurons. It is a peptide belonging to the family of gonadotropin-releasing hormone and representing the initial stage of the pituitary-hypothalamic-adrenal system. In this article, antagonists of gonadotropin-releasing hormone will also be presented.

Structure

The Nobel laureates Andrew W. Shully and Roger Guymen clarified in 1977 the identification characteristics of GnRH: pyroGlu-Gis-Trp-Ser-Tir-Gli-Le-Arg-Pro-Gly-NH2. What is common in the presentation of peptides, the sequence is given from the N-terminus to the C-terminus to represent the peptide as usual, and it is also standard to skip the notation of chirality, suggesting that the amino acids in their L-form are located. The aforementioned abbreviations refer to the proteinogenic amino acids as standard. The exception is pyroGlu - pyroglutamic acid, a derivative of glutamic acid. At the C-terminus, NH2 indicates that the chain ends with carboxydamine instead of free carboxylate.

Synthesis

The precursor of gonadotropin-releasing hormone gene GNRH1 is located in chromosome 8 of 8. Normal mammalian decapeptide synthesizes 92 amino acids of pre-prohormone in the anterior preoptic part of the hypothalamus. It is the target for various mechanisms of the regulation of the pituitary-hypothalamic-adrenal axis system, which are inhibited by the increase in the level of estrogen in the body.

Functionality

Gonadotropin-releasing hormone is secreted into the portal portal blood flow pituitary areas of the median elevation. GnRH is transferred to the pituitary gland by portal vein flow containing gonadotropic cells, where its own receptors activate GnRH, gonadotropin-releasing hormone receptors, 7 transmembrane receptors that are conjugated with G protein and stimulating beta-isoform phosphoinositide phospholipase C, leading to the mobilization of protein kinase C and calcium . This causes the activation of proteins that are involved in the secretion and synthesis of gonadotropins of FSH and LH. During proteolysis, GnRH is cleaved within a few minutes. In childhood, her activity is very low, increasing in adolescence or puberty. The success of the reproductive function depends on the pulsative activity, which is a critical, controlled feedback loop. But the activity of GnRH during pregnancy is not required. Disease or dysfunction, as well as organic damage such as trauma and tumors of the pituitary and hypothalamus, can cause impairment of pulsatile activity. Elevated levels of prolactin reduced the activity of GnRH, and hyperinsulinemia, it increases and causes a violation of the activity of FSH and LH, such as in polycystic ovaries. Cullman's syndrome is characterized by the lack of synthesis of GnRH.

Neurohormones

GnRH can be attributed to neurohormones. Gonadotropin-releasing hormone is produced in the preoptic zone of the hypothalamus, which contains most of the secreting GnRH neurons. These neurons occur in the tissues of the nose and migrate to the brain, where they are scattered in the medial septum and then combined in the hypothalamus with long dendrites, more than 1 mm long. In the synchronization of the release of GnRH, they are assisted by bundling into bundles to obtain a single synaptic input. With the help of several different transmitters, for example, GABA, glutamate and norepinephrine, GnRH-secreting neurons are regulated. Narimer, after the administration of estrogen-progesterone in women, dopamine stimulates the release of LH; Also after ovariectomy in women, dopamine can suppress the release of LH. The most important regulator of GnRH release of cis-peptin can also be regulated by estrogen. However, the existence of neurons secreting the cis-peptin and expressing also the estrogen alpha receptors was noted.

It is important to know which hormone gonadotropin-releasing hormone agonists exist. This article will contain information about this.

Influence on other organs

The role of GnRH in the processes of life other than the pituitary and hypothalamus poorly studied. It is likely that it affects the sex glands and placenta. Also, GnRH receptors and GnRH itself have been detected in cancer cells of the ovaries, endometrium, prostate and breast.

Impact on behavior

On behavior, the production of the hormone GnRH also affects. The family of cichlid fish showing social dominance experiences an intensified regulation of GnRH secretion, when socially dependent cichlids have a decrease in the regulation of GnRH secretion. The size of neurons secreting GnRH is dependent on behavior and social environment. More isolated males have a large size of GnRH secreting neurons, but males are less isolated. Also, breeding females have a smaller size of neurons than females of the control group. This indicates the social regulation of the hormone GnRH.

Gonadotropin-releasing hormone agonists will be discussed below.

Medical application

For the treatment of patients previously prescribed natural GnRH in the form of hydrochloride gonadorelin (Faktrel) and diacetate tetrahydrate gonadorelin, (Cystorelin). Modification of the structure of the GnRH decapidide led to the creation of analogues that stimulate or suppress gonadotropins to increase the half-life. And these synthetic analogues were replaced by a natural hormone. Leiprorelin analog is used for the treatment of endometriosis, breast carciomas, prostate carciomas, and also after some studies of the 1980s, including those conducted by Dr. Florence Komite from the University of Yale, for the treatment of premature puberty in the form of continuous infusion.

Gonadotropin-releasing hormone: price

The average cost per vial is from 300 rubles.

Sexual behavior of animals

Differences in sexual behavior are also due to GnRH activity. For example, the increased demonstrative sexual behavior of females causes an increase in the GnRH level. In the white-headed zoonotrichia, the requirement of copulation is increased after the introduction of GnRH, and in mammals the demonstrative sexual behavior in females is increased, which can be observed by the long-tailed white tooth and its latent reduced period when the posterior part is shown to the male and the tail moves in its direction. The testosterone activity of males increases the increased GnRH by exceeding the activity of the normal level of testosterone. The deterioration in the work of GnRH causes an aversive effect of reproductive physiology and maternal behavior. If we compare female mice, then under normal GnRH system, females take more care of the offspring than with a reduced number of neurons by 30%. Most likely, these mice will leave the mice separately, which will lead to longer searches for them.

Application in veterinary medicine

Where is gonadotropin-releasing hormone used? Preparations are used in veterinary medicine as a remedy for the treatment of cystic ovary disease in cattle. And its synthetic analogue, deslorelin, is used for veterinary control of reproductive functions with the help of an implant and sustained release of the drug.

Consider analogues of gonadotropin-releasing hormone.

Gonadotropin-releasing hormone agonists and antagonists

Separately, there is a group of drugs that, by the mechanism of action, can rightfully be called a gonadotropin-releasing hormone agonist. This means that the effect of this group of drugs on the pituitary gland produces an effect identical to that of its own hormone. Representatives of this group can be called: "Sinarel", "Lucrin Depoy Gonapeptil". These are gonadotropin-releasing hormone agonists. The drugs are used before and after the therapy of myoma, the treatment of endometriosis surgically and before the removal of the uterus (hysterectomy) in the treatment of infertility. Active substances under the influence of gastric juice disintegrate and therefore all drugs are injected under the skin, interranasole or into the muscle.

Gonadotropin-releasing hormones to antagonists include "Cetrotide" ("Cetroteriks"), "Ganirelix", etc.