Gonadotropin releasing hormone

Gonadotropin-releasing hormone (GnRH) is the central neuroendocrine regulator of the hypothalamic-pituitary-gonadal axis.

What is Gonadotropin releasing hormone? – GnRH Hormone definition

Gonadotropin releasing hormone regulates the secretion of LH(luteinizing hormone) and FSH(follicle stimulating hormone) from the anterior pituitary. The GnRH is produced by hypothalamus and supplied through the bloodstream to the pituitary gland. Parts of the brain send out neural inputs which control the secretion of GnRH. In females, the secretion in particular is controlled by sex steriods through negative feedback. In addition, the hormone causes the release of progesterone and estrogen in ovaries. In males, GnRH causes the testicles to produce testosterone.

Structure Of Gonadotropin releasing hormone

Gonadotropin releasing hormones are tropic peptide hormones manufactured and released from the GnRH neurons inside the hypothalamus. This tropic peptide is classified under the family of gonadotropin-releasing hormone establishing the inceptive step in the hypothalamic–pituitary–gonadal axis.

Also known as the luteinizing hormone-releasing hormone, GnRH is a neurohormone comprising 10 amino acids produced in the arcuate nuclei of hypothalamus.

Structure – pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2

It is ordered from the amino acid terminus to the carboxyl terminus. It is given in the standard form right from the peptide representation, to the omission of selection of chirality(assuming existence of amino acids in L-form). At the carboxyl terminus, the NH2 denotes it terminates as a carboxamide rather than a free carboxylate. Also, the standard acronym for equivalent proteinogenic amino acids are provided except for pyroGlu. It refers to a derivative of glutamic acid – pyroglutamic acid.

GnRH Function

These hormones are produced in the hypophyseal bloodstream at the structure where hypothalamus secretions take place – median eminence. Portal blood supplies Gonadotropin releasing hormones to the pituitary gland containing gonadotrope cells activating GnRHR or gonadotropin-releasing hormone receptor which is a G-protein-coupled receptor(seven-transmembraned) triggering Phosphoinositide phospholipase C(beta isoform of it) mobilizing protein kinase C and calcium. This leads to the protein-activation in the manufacturing and production of FSH and LH. In a matter of some minutes, proteolysis causes the degradation of GnRH.

In childhood, the activity of the hormone is extremely low. It is hence activated in adolescence or puberty. Action of GnRH is pivotal for reproductive functions to be operational; however, it’s action is not necessary once a pregnancy has occurred.

LH and FSH Regulation

GnRH triggers the production and secretion of FSH and LH at the pituitary. They are regulated by metrics – size, frequency of the GnRH pulses in addition to the feedback received from the strogens and the androgens. FSH is released with a favourable condition of GnRH pulses which are at a low frequency while LH pulse production is triggered by GnRH pulses which are at a higher frequency parallely.

GnRH secretion differs in men and women. In women, pulse frequency fluctuates in the cycle of menses wherein a big surge of the GnRH is observed before ovulation. In males however, this hormone is produced in pulses with a consistent/stable frequency.

In vertebrates, the secretion of this hormone is vital for proper functioning of the reproductive system. Therefore, GnRH1 – single hormone regulates a complicated process of ovulation, follicular growth, spermatogenesis in the male and maintenance of corpus luteum in females.

GnRH As A Neurohormone

It is considered as a neurohormone being secreted in a particular neural cell and liberated at its neural terminal. A specific preoptic region of the hypothalamus composed of GnRH-secreting neurons is a key region for its production. These neurons arrive from the nose and move to the brain wherein they disperse all through the hypothalamus and medial septum. Through this phenomena, synaptic input is received enabling the sync-release of GnRH.

Transmitters such as glutamate, GABA, norepinephrine are used by several afferent neurons to control the GnRH neurons. For example, in the estrogen-progesterone-primed females, dopamine seems to trigger the release of LH via GnRH. Dopamine can obstruct the liberation in ovariectomized females. Estrogen can also regulate the release of Gonadotropin releasing hormone. Seemingly, Kisspeptin is a significant regulator of GnRH release.

What Are Gonadotropin-releasing Hormone antagonists or GnRH Antagonists?

These are a medication-class antagonizing the GnRH receptor(gonadotropin-releasing hormone receptor) and subsequently the activities of the GnRH. The GnRH antagonists are beneficial to treat uterine fibroids, endometriosis, assisted reproductive technologies addressing female infertility issues, prostate cancer and other concerns.

Several GnRH antagonists resemble the natural structure of GnRH, for instance cetrorelix. However, these have an antagonistic impact. Whereas relugolix and elagolix – GnRH antagonists are small molecule compounds that are non-peptide. In order to bind to the GnRH receptors, these antagonists face the natural GnRH hence blocking the action of GnRH in the body.

Gonadotropin-releasing hormone Levels

Excess Levels Of GnRH

Impact of excessive levels of GnRH is not known yet but rarely the condition of pituitary adenomas can develop. This increases the production of gonadotropins resulting in the overproduction of estrogen and testosterone.

Lowered Levels Of GnRH

In childhood, deficiency of this hormone indicates that the person may not undergo puberty. Kallmann’s syndrome, a rare genetic condition, is an example known to lead to a loss of development of GnRH-producing nerve cells with a consequential loss of development of puberty and sexual maturation. More commonly, seen in men than women, leading to a loss of development of the testis and in women, the ovaries and hence infertility.

Damage to hypothalamus can also lead to a lack in the GnRH secretion that can halt the normal production of LH and FSH. In women, this results in loss of menstrual cycles, in men, loss of sperm production and overall, loss of hormones in ovaries and testes.

Summarizing

GnRH is secreted from hypothalamic cells. These hormones are then let into the blood stream into the blood vessels carrying the hormone to the pituitary gland. In response, the pituitary gland releases the FSH and LH which are critical for the normal health of male and female reproductive systems.

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