Gonadotropin Releasing Hormone

Introduction: What is Gonadotropin Releasing Hormone?

Gonadotropin releasing hormone (GnRH) is a hormone which is produced in the hypothalamus and transported through the bloodstream to the pituitary gland. GnRH regulates the release of the anterior pituitary Follicle Stimulating Hormone (FSH) and the luteinizing hormone (LH).

GnRH secretion is regulated by neural input from other parts of the brain and particularly in females by negative feedback from the sex steroids

GnRH Structure:

The GnRH Structure was identified by the Nobel Laureates Roger Guillemin and Andrew V. Schally in 1977.

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

The sequence is given from the amino terminus to the carboxyl terminus, as it is standard for peptide representation.

Standard presentation represents the absence of chirality classification, considering all amino acids are in their L-shape.

The abbreviations are the normal abbreviations for the corresponding proteinogenic amino acids, with the exception of pyroGlu, which relates to pyroglutamic acid, a glutamic acid derivative. The NH2 at the carboxyl terminal shows that it begins as a carboxylate instead of ending as a free carboxylate.

Synthesis of Gonadotropin Releasing Hormone:

The gene, GNRH1, is located on chromosome 8 for the precursor GnRH. In primates, in the preoptic anterior hypothalamus, the linear decapeptide end - product is synthesized from a preprohormone of 89 amino acids. It is the target of the hypothalamic – pituitary –gonadal axis' different regulatory mechanisms, such as being inhibited by increased levels of estrogen in the body.

GnRH Functions:

GnRH is secreted at median eminence in the hypophysical bloodstream portal. The blood portal takes the GnRH to the pituitary gland, which comprises the gonadotropic cells, where GnRH stimulates its own receptor.

Gonadotropin - releasing hormone receptor (GnRHR), a G - protein - coupled seven-transmembrane receptor that activates the phospholipase C beta isoform, which then mobilizes calcium and protein kinase C.

GnRH behavior during childhood is very low, and activated in adolescence or puberty. Pulse activity is critical for successful reproductive function during the reproductive years, as regulated by feedback loops. However, GnRH activity is not required as soon as a pregnancy is established.

Hypothalamic - pituitary disorder may interrupt pulsative behavior, either by disruption (i.e., hypothalamic suppression) or by organic lesions (trauma, tumour). Elevated levels of prolactin decrease activity with GnRH. In contrast, as seen in polycystic ovary syndrome ( PCOS), hyperinsulinemia increases pulse activity which leads to disorderly LH and FSH activity.

GnRH development in Kallmann syndrome is congénitally missing.

Control of FSH and LH

At the pituitary, GnRH stimulates follicle - stimulating hormone (FSH) development and secretion, and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by the androgens and estrogens feedback.

There are differences between females and males in GnRH secretion. In males, GnRH is secreted at a constant frequency in pulses; of females, though, the duration of the pulse’s changes during the menstrual cycle, and a significant burst in GnRH happens just before ovulation.

In all vertebrates, GnRH secretion is pulsative and is necessary for proper reproductive function. Thus, a single hormone, GnRH1, controls a complex process of follicular growth, ovulation, and maintenance of corpus luteum in the female, and male spermatogenesis.

Neuro Hormone:

GnRH is thought to be a neurohormone, a hormone produced in a particular neural cell and released on its neural terminal. A key area for GnRH production is the hypothalamus preoptic area, which contains the majority of the GnRH-secreting neurons.

Many specific afferent neurons control the GnRH neurons, using several common transmitters (including norepinephrine, GABA, and glutamate). For eg, dopamine in estrogen-progesterone-primed females tends to trigger the release of LH (through GnRH); dopamine can inhibit the release of LH in ovaries of females.

Kisspeptin seems an effective GnRH release regulator.

Oestrogen also can control the release of GnRH. Kisspeptin-producing neurons have been reported to also express the alpha estrogen receptor.

GnRH is located in tissues outside the hypothalamus and pituitary and is poorly understood for its function in other life processes. For example, GnRH1 is likely to play a role in both the placenta and in the gonads. Receptors of GnRH and GnRH are also found in breast, ovary, prostate and endometrial cancers.

Medical Uses of Gonadotropin Releasing Hormone

• Natural GnRH has been historically recommended for use in the treatment of human diseases as gonadorelin hydrochloride (Factrel) and gonadorelin diacetate tetrahydrate (Cystoreline).

• The synthetic analogs of gonadotropin releasing hormone have replaced the natural hormone in clinical use.

• The leuprorelin analog is used for continuous infusion, in the treatment of breast cancer, endometriosis, prostate cancer.

• It has been used for managing precocious puberty.

• In terms of menstruation regeneration or repair, premature ovarian failure and ovulation, GnRH agonists tend to be effective in protecting the ovaries throughout chemotherapy.