Gonadotropin-releasing hormone (GnRH) is known as a hormone that releases the luteinizing hormone (LHRH) and luliberin, which is a peptide trophic hormone and is responsible for the release of FSH (follicle-stimulating hormone) and (LH) luteinizing hormone from adenohypophysis. GnRH is a hormone synthesized and released in the hypothalamus from GnRH neurons. This is a peptide that belongs to the gonadotropin-releasing hormone family and represents the initial stage of the pituitary-hypothalamic-adrenal system. Gonadotropin-releasing hormone antagonists will also be presented in this article.
Structure
Nobel laureates Andrew W. Schally and Roger Guillaume specified in 1977 the identification characteristics of GnRH: pyroGlu-Gis-Trp-Ser-Tir-Gli-Lei-Arg-Pro-Gli-NH2. As is common in the presentation of peptides, the sequence is given from the N-terminus to the C-terminus for the presentation of the peptide, as usual, and it is also standard to skip the chirality designation, assuming that the amino acids are in their L-form. The above abbreviations are standard proteinogenic amino acids. The exception is pyroGlu - pyroglutamic acid, a derivative of glutamic acid. At the C-terminus, NH2 indicates that the chain ends with a carboxidamine instead of a free carboxylate.
Synthesis
The precursor of gonadotropin-releasing hormone, the GNRH1 gene, is located on chromosome 8. The normal mammalian decapeptide is synthesized by 92 amino acids of pre-prohormone in the anterior preoptic region of the hypothalamus. It is a target for various mechanisms of regulation of the pituitary-hypothalamic-adrenal axis system, which are inhibited when estrogen levels increase in the body.
Functionality
Gonadotropin-releasing hormone is secreted into the bloodstream of the portal vein by the pituitary region of the median elevation. GnRH is transferred to the pituitary by the bloodstream of the portal vein containing gonadotropic cells, where its own receptors activate GnRH, gonadotropin releasing hormone receptors, 7 transmembrane receptors that are coupled to the G protein and stimulate the beta isoform of phosphoinositide phospholipase C, which transfers to calcium mobilization . This causes activation of proteins that are involved in the secretion and synthesis of FSH and LH gonadotropins. During proteolysis, GnRH breaks down in a few minutes. In childhood, its activity is very low, increasing in adolescence or puberty. The success of reproductive function depends on the pulsative activity, which is critical, driven by a feedback loop. But GnRH activity during pregnancy is not required. Diseases or dysfunction, as well as organic damage such as injuries and tumors of the pituitary gland and hypothalamus, can cause a disturbance in pulsative activity. An increased level of prolactin decreases the activity of GnRH, and it increases with hyperinsulinemia and causes a violation of the activity of FSH and LH, as, for example, with polycystic ovary. Kallman's syndrome is characterized by the absence of GnRH synthesis.
Neurohormones
GnRH can be attributed to neurohormones. Gonadotropin-releasing hormone is produced in the preoptic zone of the hypothalamus, which contains most of the GnRH-secreting 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 connected in the hypothalamus using long dendrites, more than 1 mm long. In synchronization of GnRH release, they are assisted by bundling to obtain a single synaptic input. Using several different transmitters, for example, GABA, glutamate and norepinephrine, GnRH secreting neurons are regulated. Narpimer, after the introduction of estrogen-progesterone in women, dopamine stimulates the release of LH; also after oophorectomy in women, dopamine can inhibit the release of LH. The most important regulator of GnRH release, Kiss-Peptin, can also be regulated by estrogen. However, the existence of neurons secreting Kiss Peptin and also expressing estrogen receptors alpha was noted.
It is important to know what gonadotropin-releasing hormone agonists are. This article will provide information on this.
Impact on other organs
The role of GnRH in the vital processes except the pituitary and hypothalamus is poorly understood. It is likely that it affects the gonads and the placenta. Also, GnRH receptors and GnRH itself were found in the cancer cells of the ovaries, endometrium, prostate and breast.
Behavioral Impact
GnRH hormone production also affects behavior. A family of cichlid fishes demonstrating social dominance experiences enhanced regulation of GnRH secretion, when socially dependent cichlids have a decreased regulation of GnRH secretion. The size of neurons secreting GnRH is dependent on behavior and social environment. More isolated males have a larger size of GnRH-secreting neurons, while ches males are less isolated. Breeding females also have a smaller neuron size than females of the control group. This suggests the social regulation of the hormone GnRH.
Gonadotropin-releasing hormone agonists will be discussed below.
Medical use
For the treatment of sick people, natural GnRH was previously prescribed in the form of gonadorelin hydrochloride (Factrel) and gonadorelin diacetate tetrahydrate, (Cystorelin). Modification of the structure of GnRH decapiptide led to the creation of analogues that stimulate or suppress gonadotropins to increase the half-life. And with these synthetic analogs, the natural hormone has been replaced. The leuprorelin analog is used to treat endometriosis, breast carcinoma, prostate carcinoma, and also after some studies of the 1980s, including those conducted by Dr. Florence Komit of Yale University, for the treatment of premature puberty in the form of a continuous infusion.
Gonadotropin releasing hormone: price
The average cost of one bottle is from 300 rubles.
Animal sexual behavior
Differences in sexual behavior are also due to GnRH activity. For example, increased demonstrative sexual behavior in females causes an increase in GnRH levels. In white-headed zonotrichia, the requirement for copulation increases after administration of GnRH, and in mammals, demonstrative sexual behavior in females is enhanced, which can be observed by the long-tailed shrew and its latent reduced period when the back of the male is demonstrated and the tail moves in its direction. Male testosterone activity enhances increased GnRH by exceeding the activity of normal testosterone levels. Deteriorated GnRH function causes an aversive effect of reproductive physiology and maternal behavior. If we compare female mice, then with a normal GnRH system, females care more about offspring than with a reduced number of neurons by 30%. Most likely, such mice will leave mice separately, which will lead to longer searches.
Veterinary use
Where is gonadotropin releasing hormone used? The drugs are used in veterinary medicine as a tool in the treatment of cystic ovarian disease in cattle. And its synthetic analogue, deslorelin, is used for veterinary control of reproductive functions with the help of an implant and a delayed release of the drug.
Consider analogues of gonadotropin-releasing hormone.
Gonadotropin-releasing hormone agonists and antagonists
A group of drugs is singled out separately, which 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 causes an effect identical to the effect 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 treatment of fibroids, surgical treatment of endometriosis and before removal of the uterus (hysterectomy) in the treatment of infertility. Active substances disintegrate under the influence of gastric juice and therefore all drugs are administered under the skin, intranasol or into the muscle.
Gonadotropin-releasing hormone antagonists include Cetrotide (Cetroterix), Ganirelix, etc.