|March 26, 2016|
Protbox header |Name=Gonadotropin-releasing hormone
|Codes=EntrezGene|2796, RefSeq|NM_000825, UniProt|P01148, OMIM|152760
Gonadotropin releasing hormone (GnRH) is a peptide hormone responsible for the release of follicle-stimulating hormone|FSH and luteinizing hormone|LH from the anterior pituitary. GnRH is synthesized and released by the hypothalamus.
The gene for the GnRH precursor is located on chromosome 8. This precursor contains 92 amino acids and is processed to GnRH, a decapeptide (10 amino acids).
The identity of GnRH was clarified by the 1977 Nobel Laureates Roger Guillemin and Andrew V. Schally:
Protbox header |Name=gonadotropin-releasing hormone receptor
|Codes=EntrezGene|2798, RefSeq|NM_000406, UniProt|P30968, OMIM|138850
GnRH is considered a neurohormone, a hormone produced in a specific neural cell and released at its neural terminal. A key area for production of GnRH in the hypothalamus is the preoptic area, that contains most of the GnRH secreting neurons. GnRH is secreted in the portal bloodstream at the level of the median eminence, the gonadotropes, and activates receptors in the cell wall. GnRH is degradated by proteolysis within a few minutes.
In the pituitary GnRH stimulates synthesis and release of FSH and LH, a process that is controlled by the frequency and amplitude of GnRH pulses, as well as the feedback of androgens and estrogens.
Sex differences exist in the GnRH secretion in male and female: in particular, in the male GnRH is secreted in pulses at a constant frequency, while in the female the frequency of the pulses varies during the menstrual cycle and a surge of GnRH is observed before the ovulation.
The pulsatility of GnRH secretion has been seen in all vertebrates, and it is necessary to ensure a correct reproductive function.
Thus a single hormone, GnRH, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male.
GnRH activity is very low during childhood. During the reproductive years pulse activity is critical for successful reproductive function as controlled by feedback loops. However, once a pregnancy is established GnRH activity is not required. Pulse activity can be disrupted by hypothalamic-pituitary disease, either dysfunction (i.e hypothalamic suppression) or organic lesions (trauma, tumor). Elevated prolactin levels decrease GnRH activity. In contrast hyperinsulinemia increases pulse activity leading to disordery LH and FSH activity as seen in PCOS. GnRH formation is congenitally absent in Kallmann syndrome. Dopamine appears to decrease GnRH activity.
GnRH is found in organs outside of the hypothalamus and pituitary and its role in other life processes is poorly understood. For instance, there is likely to be a role for GnRH in the placenta and in the gonads.
GnRH is available as gonadorelin hydrochloride (Factrel) for injectable use. Studies have described it being used via an infusion pump system to induce ovulation in patients with hypothalamic hypogonadism.
While GnRH has been synthesized and become available, its short half life requires infusion pumps for its clinical use. Modifications of the decapeptide structure of GnRH have led to GnRH analog|analog medications that either stimulate (GnRH agonists) or suppress (GnRH antagonists) the gonadotropins. Importantly, through downregulation agonists are also able to exert a prolonged suppression effect.
Category:Hormones of the hypothalamus
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