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Gonadotropin-releasing HormoneGonadotropin Releasing Hormone (GnRH) is a peptide hormone responsible for the release of FSH and LH from the anterior pituitary. GnRH is synthesized and released by the hypothalamus. Gene 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). Structure The identity of GnRH was clarified by the 1977 Nobel Laureates Roger Guillemin and Andrew V. Schally: pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly CONH2. GnRH as a neurohormone 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 arcuate nucleus. GnRH is transported in the portal bloodstream to the target, the gonadotropes, and activates receptors in the cell wall. GnRH is degradated by proteolysis within a few minutes. Control of FSH and LH 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. 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. This process utilizes feedback loops to regulate GnRH pulse activity. Activity 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 in other organs 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. Agonists and antagonists While GnRH has been synthesized and become available, its short half life require infusion pumps for its clinical use. Modifications of the decapeptide structure of GnRH have led to 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.
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