Central precocious puberty (CPP) is caused by the premature reactivation of the hypothalamic-pituitary-gonadal axis. Genetic, nutritional, and environmental factors play a crucial role in determining pubertal timing. Recently mutations in kisspeptin (KISS1), kisspeptin receptor (KISS1R), and makorin RING finger protein 3 (MKRN3) genes have been identified as genetic causes of CPP. In particular, the MKRN3 gene is known to affect pubertal initiation. The MKRN3 gene is located on chromosome 15q11-q13 in the Prader-Willi syndrome (PWS) critical region. MKRN3 deficiency, due to a loss of function mutation, leads to the withdrawal of hypothalamic inhibition and prompts pulsatile gonadotropin-releasing hormone secretion, resulting in precocious puberty. The exact functions of these genes associated with CPP are still not well understood. Larger studies are required to discover the mechanisms involved in pubertal development.
Fingers ; Gonadotropin-Releasing Hormone ; Kisspeptins ; Prader-Willi Syndrome ; Puberty, Precocious*

Central precocious puberty (CPP) is caused by the premature reactivation of the hypothalamic-pituitary-gonadal axis. Genetic, nutritional, and environmental factors play a crucial role in determining pubertal timing. Recently mutations in kisspeptin (KISS1), kisspeptin receptor (KISS1R), and makorin RING finger protein 3 (MKRN3) genes have been identified as genetic causes of CPP. In particular, the MKRN3 gene is known to affect pubertal initiation. The MKRN3 gene is located on chromosome 15q11-q13 in the Prader-Willi syndrome (PWS) critical region. MKRN3 deficiency, due to a loss of function mutation, leads to the withdrawal of hypothalamic inhibition and prompts pulsatile gonadotropin-releasing hormone secretion, resulting in precocious puberty. The exact functions of these genes associated with CPP are still not well understood. Larger studies are required to discover the mechanisms involved in pubertal development.
Fingers ; Gonadotropin-Releasing Hormone ; Kisspeptins ; Prader-Willi Syndrome ; Puberty, Precocious*

Puberty is the end-point of a complex series of developmental events, defined by the dynamic interaction between genetic factors and environmental cues, ultimately leading to the attainment of reproductive capacity. Kisspeptins, products of the KISS1 gene, were originally identified as metastasis suppressor peptides with the ability to bind G protein-coupled receptors (GPR54). In 2003, loss-of-function mutations of the GPR54 gene were found in patients with hypogonadotropic hypogonadism. This finding triggered study of the role of the kisspeptin/GPR54 system as an essential gatekeeper of control of reproduction and pubertal development. Kisspeptins are very potent elicitors of gonadotropin secretion, primarily through stimulation of gonadotropin-releasing hormone release. KISS1 also functions as an essential integrator for peripheral inputs, including gonadal steroids and nutritional signals, and for controlling GnRH and gonadotropin secretion. Whether the kisspeptin/GPR54 system is the trigger for puberty onset and/or it operates as integrator and effector of up-stream regulatory factors warrants further investigation.
Cues ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Gonads ; Humans ; Hypogonadism ; Kisspeptins ; Leptin ; Neoplasm Metastasis ; Peptides ; Puberty ; Reproduction ; Steroids

Puberty is the end-point of a complex series of developmental events, defined by the dynamic interaction between genetic factors and environmental cues, ultimately leading to the attainment of reproductive capacity. Kisspeptins, products of the KISS1 gene, were originally identified as metastasis suppressor peptides with the ability to bind G protein-coupled receptors (GPR54). In 2003, loss-of-function mutations of the GPR54 gene were found in patients with hypogonadotropic hypogonadism. This finding triggered study of the role of the kisspeptin/GPR54 system as an essential gatekeeper of control of reproduction and pubertal development. Kisspeptins are very potent elicitors of gonadotropin secretion, primarily through stimulation of gonadotropin-releasing hormone release. KISS1 also functions as an essential integrator for peripheral inputs, including gonadal steroids and nutritional signals, and for controlling GnRH and gonadotropin secretion. Whether the kisspeptin/GPR54 system is the trigger for puberty onset and/or it operates as integrator and effector of up-stream regulatory factors warrants further investigation.
Cues ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Gonads ; Humans ; Hypogonadism ; Kisspeptins ; Leptin ; Neoplasm Metastasis ; Peptides ; Puberty ; Reproduction ; Steroids

Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.
Adult ; Dynorphins ; Fertility ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism ; Hypothalamus ; Infertility ; Kisspeptins ; Mammals ; Neurokinin B ; Neuropeptides ; Nutritional Status ; Axis, Cervical Vertebra

OBJECTIVETo investigate the gene expression of Kiss-1 in the hypothalamus of true precocious female rats at various stages of development.

METHODSForty 5-day-old normal female Sprague-Dawley rats were randomly assigned into four groups of 10 rats: Control group 1, Control group 2, Model group 1 and Model group 2. The rats from the two model groups were injected with 300 microg of danazol at 5 days of age to induce true precocious puberty. The two control groups were injected with normal saline instead. For the determination of Kiss-1 mRNA expression in the hypothalamus, the rats of the Model group 1 were sacrificed during the first diestrus (early puberty) and meanwhile the rats of the Control group 1 were sacrificed when they were at prepuberty; the Control group 2 rats were sacrificed at the first diestrus (early puberty); the rats of the Model group 2 were sacrificed during the second diestrus (middle puberty). The expression of Kiss-1 mRNA in the hypothalamus in the four groups was detected using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).

RESULTSKiss-1 mRNA expression in the hypothalamus in Model group 1 and Model group 2 increased by 1.4-fold and 2.8-fold, respectively, compared with that of Control group 1 (P < 0.05). Model group 2 showed significantly higher Kiss-1 mRNA levels than Model group 1 (P < 0.05). There were no statistical differences in the Kiss-1 mRNA expression between Control group 2 and Model group 1.

CONCLUSIONSGene expression of Kiss-1 is associated with the developmental period of true precocious puberty, suggesting that Kiss-1 might play a role in the pathogenesis of this disorder.

Animals ; Female ; Hypothalamus ; metabolism ; Kisspeptins ; Luteinizing Hormone ; blood ; Proteins ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Sexual Maturation ; physiology

OBJECTIVETo investigate the expression and clinical significance of KiSS- 1 and E- cadherin in gastric cardia carcinoma and the correlation between the two proteins.

METHODSThe expression of KiSS- 1 and E- cadherin in 80 patients with gastric cardia carcinoma and 20 patients with normal gastric cardia epithelium was detected by immunohistochemical technique.

RESULTSThe expression of KiSS- 1 was negatively correlated with lymphatic metastasis and clinical stage (P < 0.05), but not correlated with the cancer differentiation (P < 0.05). The expression of E- cadherin was negatively correlated with lymphatic metastasis, clinical stage, and cancer differentiation (P < 0.05). Spearman test showed a positive correlation between KiSS- 1 and E- cadherin expression (r(s)=0.722, P < 0.05).

CONCLUSIONKiSS- 1 and E- cadherin may play important roles in inhibiting the invasion and metastasis of gastric cardia carcinoma.

Adult ; Aged ; Aged, 80 and over ; Cadherins ; metabolism ; Cardia ; pathology ; Female ; Humans ; Kisspeptins ; Male ; Middle Aged ; Neoplasm Metastasis ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo assay the expression of KiSS-1 and GnRH in the male rat hypothalamus at different developmental stages, and to explore the significance of KiSS-1 in sex development onset and normal reproduction regulation.

METHODSExpression analyses of KiSS-1 and GnRH genes were conducted in the rat hypothalamus at different developmental stages with RT-PCR and real time-PCR. The testosterone level was assayed by chemoluminescence technique.

RESULTSKiSS-1 mRNA rose gradually during sex development in the rat hypothalamus, highest at puberty and lowered a little at adulthood. KiSS-1 mRNA of the prepubertal, early pubertal, pubertal and adult rats was 1.7, 2.1, 3.5 and 2.0 times higher than that of the infantile rats respectively. The expression of GnRH and KiSS-1 correlated positively (r = 0.905, P < 0.05). But the activation of GnRH neuron was later than KiSS-1. The expression of GnRH was the highest in the puberty rats. GnRH mRNA of the prepubertal, early pubertal, pubertal and adult rats was 1.1, 1.94, 2.42 and 1.92 times higher than that of the infantile rats respectively. The level of testosterone in the adult rats was significantly higher than that at the earlier stage and was the highest at the adult stage.

CONCLUSIONThe expression of KiSS-1 correlates positively with that of GnRH. KiSS-1 may participate in the regulation of GnRH and is relevant to puberty onset and the regulation of reproduction function.

Animals ; Gonadotropin-Releasing Hormone ; biosynthesis ; genetics ; Hypothalamus ; metabolism ; Kisspeptins ; Male ; Proteins ; metabolism ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

Humans ; Kisspeptins ; Lymphatic Metastasis ; genetics ; Matrix Metalloproteinase 9 ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; enzymology ; metabolism ; pathology ; Tumor Suppressor Proteins ; genetics

OBJECTIVETo investigate the change of expression level of metastasis suppressor gene Kiss-1 in the colorectal cancer cell line SW480 after radiation, and to determine its association with the proliferation and apoptosis of SW480 cells.

METHODSSW480 cells were divided into control group (0 Gy) and study groups (2, 4, 6, 8 Gy). Cells in the study groups were irradiated by 6-MV X-ray radiation for 48 hours. Immunohistochemistry and real-time PCR methods were used to investigate the influence of radiation on Kiss-1 gene expression of SW480. Colony formation assay was used to detect the proliferation of SW480. Flow cytometry-Annexin- V/PI assay was used to observe the change of the apoptosis rate.

RESULTSCompared with the control group, Kiss-1 protein expression increased after radiation of 6, 8 Gy (P<0.05), but no significant changes were observed after radiation of 2, 4 Gy(P>0.05). Kiss-1 gene mRNA level increased after radiation of 2, 4, 6 Gy, while no obvious change was observed for 8 Gy radiation. The apoptosis rates increased for 4, 6, 8 Gy radiation(P<0.05), however, there was no significant difference for 2 Gy radiation (P<0.05).

CONCLUSIONRadiation may increase Kiss-1 gene expression in SW480 cells, which results in decreases proliferation and increases apoptosis in residual surviving cells.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; pathology ; Humans ; Kisspeptins ; genetics ; metabolism ; radiation effects ; RNA, Messenger ; genetics ; X-Rays