Gonadotropin-releasing Hormone

gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone, a neurohormone consisting of 10 amino acids that is produced in the arcuate nuclei of the hypothalamus. GnRH stimulates the synthesis and secretion of the two gonadotropins—luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—by the anterior pituitary gland. The effects of GnRH on the secretion of LH and FSH are not exactly parallel, and the variations are probably due to other modulating factors such as the serum concentrations of steroid hormones (substances secreted by the adrenal cortex, testes, and ovaries).

Characteristic of all releasing hormones and most striking in the case of GnRH is the phenomenon of pulsatile secretion. Under normal circumstances, GnRH is released in pulses at intervals of about 90 to 120 minutes. In order to increase serum gonadotropin concentrations in patients with GnRH deficiency, the releasing hormone must be administered in pulses. In contrast, constant administration of GnRH suppresses gonadotropin secretion, which has therapeutic benefits in certain patients, such as children with precocious puberty and men with prostate cancer.

The neurons that secrete gonadotropin-releasing hormone 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. In rats that are deprived of their pituitary gland and ovaries but are given physiological amounts of estrogen, injection of GnRH results in changes in posture characteristic of the receptive female stance for sexual intercourse.

Hypogonadism, in which the functional activity of the gonads is decreased and sexual development is inhibited, can be caused by a congenital deficiency of GnRH. Patients with this type of hypogonadism typically respond to pulsatile treatment with the hormone. Many of these patients also have deficiencies of other hypothalamic-releasing hormones. A subset of patients with hypogonadism have isolated GnRH deficiency and loss of the sense of smell (anosmia). This disorder is called Kallmann syndrome and is usually caused by a mutation in a gene that directs the formation of the olfactory (sense of smell) system and the formation of parts of the hypothalamus. Abnormalities in the pulsatile secretion of GnRH result in subnormal fertility and abnormal or absent menstruation.