Kisspeptin is a naturally occurring protein in humans that plays important roles in hormone signaling during puberty and reproduction. It is also thought to alter mood and behavior, promote angiogenesis, and regulate kidney function. Kisspeptin has also been found in the brain and is known to suppress tumor growth and spread. It is also known and heavily studied for its ability to influence gonadotropin releasing hormone (GnRH).
Gonadotropin releasing hormone is produced and secreted by specialized nerve cells in the hypothalamus of the brain. It is released into tiny blood vessels that carry this hormone from the brain to the pituitary gland, where it stimulates the production of two more hormones – follicle stimulating hormone and luteinizing hormone. These hormones are released into the general circulation and act on the testes and ovaries to initiate and maintain their reproductive functions.
Kisspeptins are a group of neuroendocrine peptides that stimulate the release of Gonadotropin Releasing Hormone (GnRH) and is involved in the regulation of developmental sex hormones at the beginning stages of puberty. There have been problems in maturation centered around receptor mutations for kisspeptin. Kisspeptins are encoded by the KISS1 gene, which was originally identified as a human metastasis suppressor gene for melanoma and breast cancer. Kisspeptins have shown therapeutic benefits regarding the upregulation of the endogenous production of Luteinizing Hormone (LH) and Follicular Stimulating Hormone (FSH) through the HPA axis. Thus, it can stimulate Leydig cells to produce testosterone without the result of hypogonadism shown with exogenous testosterone usage. The expression of Kiss1 has also been altered in other situations of energy imbalance such as obesity and diabetes. It has also been shown to reverse the effects of hypogonadotropic hypogonadism. It also shows other physiologic effects such as helping with egg implantation and maturation in reproduction, as well as the prevention of ectopic pregnancy. Further, in the kidneys it has been shown to increase aldosterone production as well as pregnenolone breakdown and kisspeptin – angiotensin2 production.
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Gonadotropin releasing hormone is produced and secreted by specialized nerve cells in the hypothalamus of the brain. It is released into tiny blood vessels that carry this hormone from the brain to the pituitary gland, where it stimulates the production of two more hormones – follicle stimulating hormone and luteinizing hormone. These hormones are released into the general circulation and act on the testes and ovaries to initiate and maintain their reproductive functions.
What is Kisspeptin?
Kisspeptins are a group of neuroendocrine peptides that stimulate the release of Gonadotropin Releasing Hormone (GnRH) and is involved in the regulation of developmental sex hormones at the beginning stages of puberty. There have been problems in maturation centered around receptor mutations for kisspeptin. Kisspeptins are encoded by the KISS1 gene, which was originally identified as a human metastasis suppressor gene for melanoma and breast cancer. Kisspeptins have shown therapeutic benefits regarding the upregulation of the endogenous production of Luteinizing Hormone (LH) and Follicular Stimulating Hormone (FSH) through the HPA axis. Thus, it can stimulate Leydig cells to produce testosterone without the result of hypogonadism shown with exogenous testosterone usage. The expression of Kiss1 has also been altered in other situations of energy imbalance such as obesity and diabetes. It has also been shown to reverse the effects of hypogonadotropic hypogonadism. It also shows other physiologic effects such as helping with egg implantation and maturation in reproduction, as well as the prevention of ectopic pregnancy. Further, in the kidneys it has been shown to increase aldosterone production as well as pregnenolone breakdown and kisspeptin – angiotensin2 production.
How does Kisspeptin work?
Kisspeptins would appear to act directly on the nerve endings of GnRH neurons to control GnRH release, pulses or discharge. Other studies show that Kisspeptins increase GnRH secretion as well as the level of mRNA. Kisspeptin is released in conjunction with two other hormones: dynorphin and neurokinin B, also called the KNDy neurons. The KNDy neurons are a fundamental element in regulating gonadotropin-releasing hormone (GnRH) pulses. These two hormones are not understood well, but early research indicates they may have a role in causing the release of kisspeptin.Research Example 1:
Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men
Intravenous bolus kisspeptin-10 resulted in a rapid and dose-dependent rise in serum LH concentration, with maximal stimulation at 1 μg/kg (4.1 ± 0.4 to 12.4 ± 1.7 IU/liter at 30 min, P < 0.001, n = 6). Administration of 3 μg/kg elicited a reduced response vs. 1 μg/kg (P < 0.05). Infusion of kisspeptin-10 at 4 μg/kg h for 22.5 h elicited an increase in LH from a mean of 5.4 ± 0.7 to 20.8 ± 4.9 IU/liter (n = 4; P < 0.05) and serum testosterone increased from 16.6 ± 2.4 to 24.0 ± 2.5 nmol/liter (P < 0.001). LH pulses were obscured at this high rate of secretion, but a lower dose infusion of kisspeptin-10 (1.5 μg/kg h) increased mean LH from 5.2 ± 0.8 to 14.1 ± 1.7 IU/liter (n = 4; P < 0.01) and increased LH pulse frequency from 0.7 ± 0.1 to 1.0 ± 0.2 pulses/h (P < 0.05) and secre- tory burst mass from 3.9 ± 0.4 to 12.8 ± 2.6 IU/liter (P < 0.05). Kisspeptin-10 boluses potently evoke LH secretion in men, and continuous infusion increases testosterone, LH pulse frequency, and pulse size. Kisspeptin analogues have therapeutic potential as regulators of LH and thus testosterone secretion.Research Example 2:
Kisspeptin and Cancer: Molecular Interaction, Biological Functions, and Future Perspectives
Cancer disease is the second leading cause of death in the world and one of the main fields of medical research. Although there is now a greater understanding of biological mechanisms of uncontrolled cell growth, invasiveness and metastasizing, the multi-step process of cancer development and evolution is still incompletely understood. The inhibition of molecules activated in cancer metastasizing is a hot topic in cancer research. Among the known antimetastatic genes, KiSS-1 is involved in the metastatic cascade by preventing growth of metastasis. Moreover, loss of KiSS-1 protein expression by tumor cells has been associated with a more aggressive phenotype. KiSS-1 gene encodes a 145-amino acid protein, which following proteolytic cleavage, generates a family of kisspeptins (Kp-10, -13, and -14), that are endogenous agonists for the G-protein-coupled receptor (GPR54). The antitumor effect of KiSS-1 was primarily associated with the inhibition of proliferation, migration and cell invasion and, consequently, the reduced formation of metastasis and intratumoral micro vessels. In this review, we highlight the latest data on the role of kisspeptin signaling in the suppression of metastasis in various cancer types and the use of modulators of KiSS/GPR54 signaling as potential novel therapeutic agents for the treatment of cancer.Research Example 3:
Kisspeptin and energy balance in reproduction
Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.Research Example 4:
