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Gonadotropin-releasing hormone

Gonadotropin-releasing hormone (GnRH), a neurohormone also known as luteinizing hormone-releasing hormone (LHRH), is a peptide chain of 10 amino acids. It stimulates the synthesis and release of the two pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). While some investigators hold that there are two types of GnRH, most evidence supports the conclusion that only one type of neuropeptide stimulates the release of the two gonadotropins and that the variations in levels of both gonadotropins in the circulation are due to other modulating factors.

Characteristic of all releasing hormones and most striking in the case of GnRH is the phenomenon of pulsatile secretion. In normal individuals, GnRH is released in spurts at intervals of about 80 minutes. The pulsatile administration of GnRH in large doses results in an ever-increasing concentration of gonadotropins in the blood. In striking contrast, the constant infusion of GnRH suppresses gonadotropin secretion. This phenomenon is advantageous for persons for whom suppression is important. Such persons include children with precocious puberty, and elderly men with cancer of the prostate. On the other hand, pulsatile administration of GnRH is efficacious in men or women in whom deficiency of gonadal function is due to impaired secretion of GnRH. A potential application of this phenomenon is the synthetic modifications of GnRH as a male as well as a female contraceptive.

Neurons that secrete GnRH have connections to an area of the brain known as the limbic system, which is heavily involved in the control of emotions and sexual activity. Studies in rats deprived of pituitary glands and ovaries but maintained on physiological amounts of female hormone (estrogen) have demonstrated that the injection of GnRH results in complex and striking changes in posture characteristic of the receptive female stance for sexual intercourse.

Some individuals have hypogonadism (in which the functional activity of the gonads is decreased and sexual development is inhibited) due to a congenital deficiency of GnRH, which responds to treatment with GnRH. Most of these people also suffer from hypothalamic disease and are deficient in other releasing hormones as well, but there are also individuals in whom GnRH deficiency is isolated and associated with a loss of the sense of smell (anosmia). Abnormalities in the pulses of GnRH secretion result in subnormal fertility, abnormal or absent menstruation, and possibly cystic disease of the ovary or even ovarian cancer.
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