Gonadotropin-releasing hormone ( GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic hormone peptide hormone synthesized and released from GnRH Neuron within the hypothalamus. GnRH is inhibited by testosterone. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.
Structure
Synthesis
Function
GnRH activity is elevating during fetal life, drops briefly following birth due to the effect of placental hormones, then becomes elevated again for the first one to six months of life in a period known as Mini-puberty, during which time gonadotropins and sex steroids contribute to the development of sexual organs. GnRH is very low during childhood, and is reactivated at puberty during adolescence. 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. Pulsatile 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 disorderly LH and FSH activity, as seen in polycystic ovary syndrome (PCOS). GnRH formation is congenitally absent in Kallmann syndrome.
Control of FSH and LH
There are differences in GnRH secretion between females and males. In males, GnRH is secreted in pulses at a constant frequency; however, in females, the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation.
GnRH secretion is pulsatile in all vertebrates, and is necessary for correct reproductive function. Thus, a single hormone, GnRH1, controls a complex process of Ovarian follicle growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male.
Neurohormone
The GnRH Neuron are regulated by many different afferent neurons, using several different transmitters (including norepinephrine, GABA, glutamate). For instance, dopamine appears to stimulate LH release (through GnRH) in estrogen-progesterone-primed females; dopamine may inhibit LH release in ovariectomized females. Kisspeptin appears to be an important regulator of GnRH release. GnRH release can also be regulated by estrogen. It has been reported that there are KNDy neuron that also express estrogen receptor alpha.
Other organs
Effects of behavior
Multiple neuronal regions in the limbic system send signals to the hypothalamus to modulate the amount of GnRH production and the frequency of pulses. This provides a possible explanation for why psychic influences typically affect female sexual function.Mills EGA, O'Byrne KT, Comninos AN. The Roles of the Amygdala Kisspeptin System. Semin Reprod Med. 2019 Mar;37(2):64-70. doi: 10.1055/s-0039-3400462. Epub 2019 Dec 17. PMID 31847026.
Medical uses
Its analogue leuprorelin is used for continuous infusion, to treat breast cancer, endometriosis, prostate cancer, and following research in the 1980s by researchers, including Dr. Florence Comite of Yale University, it was used to treat precocious puberty.
The expression of GnRH receptors in cancers has led to the use of GnRH as a targeting molecule to deliver toxins specifically to the receptor-expressing cancer cells. In a similar concept, its use to deliver toxins to pituitary gonadotropes in animals has been explored as a means of sterilization, with limited success. GnRH was also shown to successfully deliver DNA into the pituitary gonadotropes where the expressed protein blocked expression of the hormones that regulate reproduction.
A Cochrane Review is available which investigates whether GnRH analogues, given before or alongside chemotherapy, could prevent damage to women's ovaries caused by chemotherapy. GnRH agonists appear to be effective in protecting the ovaries during chemotherapy, in terms of menstruation recovery or maintenance, premature ovarian failure and ovulation.
Animal sexual behavior
An elevation of GnRH raises males' testosterone capacity beyond a male's natural testosterone level. Injections of GnRH in male birds immediately after an aggressive territorial encounter results in higher testosterone levels than is observed naturally during an aggressive territorial encounter.
A compromised GnRH system has adverse effects on reproductive physiology and maternal behavior. In comparison to female mice with a normal GnRH system, female mice with a 30% decrease in GnRH Neuron are poor caregivers to their offspring. These mice are more likely to leave their pups scattered rather than grouped together, and will take significantly longer to retrieve their pups.
Veterinary use
Other names
- Gonadotropin-releasing factor (GnRF, GRF); Gonadotropin-releasing hormone (GnRH, GRH)
- Follicle-stimulating hormone-releasing factor (FRF, FSH-RF); Follicle-stimulating hormone-releasing hormone (FRH, FSH-RH)
- Luteinizing hormone-releasing factor (LRF, LHRF); Luteinizing hormone-releasing hormone (LRH, LHRH)
- Follicle-stimulating hormone and luteinizing hormone–releasing factor (FSH/LH-RF); Follicle-stimulating hormone and luteinizing hormone-releasing hormone (FSH/LH-RH)
- Luteinizing hormone and follicle-stimulating hormone–releasing factor (LH/FSH-RF); Luteinizing hormone and follicle-stimulating hormone-releasing hormone (LH/FSH-RH)
- Gonadorelin (INN for pharmaceutical form)
- Gonadoliberin
See also
- Gonadotropin-releasing hormone receptor § Agonists
- GnRH modulator
- Progonadotropin
- Gonadotropin surge-attenuating factor
- GNRH2, a similar gene
- Gonadotropin-inhibitory hormone
- Breastfeeding and fertility
Further reading
External links
|
|
