OBJECTIVETo explore the expressions and functions of the kisspeptin/kiss1r system and GnRH in the hypothalamic arcuate nucleus (HAN) and the influence of the kisspeptin/kiss1r system on the hypothalamic-pituitary-testis (HPT) axis in the rat models of diet-induced obesity.

METHODSNinety newborn SD male rats were randomly assigned to receive normal diet (n = 30) and high-fat diet (n = 60) for the establishment of obesity models. The model rats were again equally divided into a control group and an experimental group, the latter injected with kisspeptin via the lateral ventricle. Then the body mass index (BMI) and endocrine hormone levels of the rats were recorded, the protein expressions of LepR, kisspeptin, kiss1r, and GnRH in the HAN determined by immunohistochemistry and Western blot, and the levels of GnRH mRNA in the HAN measured by qRT-PCR.

RESULTSSignificantly increased BMI and hormone levels indicated the successful establishment of diet-induced obesity models. Compared with the normal rats, the protein expressions of LepR, kisspeptin, and GnRH in the HAN were markedly decreased in the controls, and that of GnRH and the levels of LH and T significantly increased, but the expressions of LepR and kiss1r showed no remarkable changes in the experimental rats.

CONCLUSIONLateral ventricular injection of kisspeptin can upregulate obesity-induced low expression of GnRH, correct the dysfunction of the HPT axis, and thus improve reproductive function in rats.

Animals ; Arcuate Nucleus of Hypothalamus ; metabolism ; Diet, High-Fat ; Disease Models, Animal ; Female ; Gonadotropin-Releasing Hormone ; metabolism ; Hypothalamo-Hypophyseal System ; Kisspeptins ; metabolism ; Male ; Obesity ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism ; Receptors, Kisspeptin-1 ; Receptors, Leptin ; metabolism

OBJECTIVETo investigate the expression and clinical significance of KISS-1 mRNA and GPR54 mRNA in endometrial carcinoma.

METHODSThe expression of KISS-1 mRNA and GPR54 mRNA in 32 patients with endometrial carcinoma, 10 patients with endometrial intraepithelial neoplasia (EIN) and 12 patients with normal endometrium was detected by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTSThe positive rate of KISS-1 mRNA in endometrial carcinoma, EIN and normal endometrium was 37.5%, 80.0% and 83.3% respectively (endometrial carcinoma vs EIN or normal endometrium, P < 0.05). The expression of KISS-1mRNA in patients with endometrial carcinoma was correlated with its clinical stage, myometrial invasion and lymph node metastasis (P < 0.05). In endometrial carcinoma, the more advanced clinical stage, the lower expression of KISS-1 mRNA was detected. The positive rate of GPR54 mRNA in endometrial carcinoma, EIN and normal endometrium was 78.1%, 70.0% and 66.7% respectively, with no significant statistical difference (P > 0.05). It was not correlated with the clinical stage, histology grade, myometrial invasion or lymph node metastasis (P > 0.05).

CONCLUSIONThe interaction of KISS-1 and GPR54 may play an important role in inhibiting the invasion and metastasis of endometrial carcinoma.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Kisspeptins ; Middle Aged ; Neoplasm Metastasis ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, G-Protein-Coupled ; biosynthesis ; genetics ; Receptors, Kisspeptin-1 ; Tumor Suppressor Proteins ; biosynthesis ; genetics

OBJECTIVETo study the therapeutic effect of Dabuyin Wan on true precocious puberty of female rats and its possible mechanism.

METHODTwenty-two-day-old female SD rats were subcutaneously injected with 40 mg x kg(-1) N-methyl-DL-aspartic acid (NMA) at 14:00 and 16:00 every day; meanwhile, the rats were given Dabuyin Wan for intervention. Visual inspection was conducted for the time of vaginal opening. The first estrus was observed by yaginal smear test. Their ovaries and uterus were weighed to calculate organ coefficients. Conventional pathological slices were made to observe morphological changes in ovaries and uterus and calculate the thickness of uterine walls and the number of corpus luteums. The level of E2 in serum was detected to assess the therapeutic effect of Dabuyin Wan on NMA precocious puberty in rats. expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus were measured by semi-quantitative RT-PCR to investigate the possible mechanism of Dabuyin Wan.

RESULTDabuyin Wan at 3.24 g x kg(-1) and 1.62 g x kg(-1) significantly decreased the organ coefficients in rats with precocious puberty (P < 0.05), decrease the number of vaginal openings in rats (P < 0.01) and the thickness of uterine walls and the number of corpus luteums (P < 0.05), and notably down-regulated expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus (P < 0.05), without significant impact on E2 in serum.

CONCLUSIONDabuyin Wan may inhibit GnRH synthesis and release as well as startup of hypothalamic-pituitary-gonadal axis by down-regulating Kiss-1/GPR54 mRNA expression in hypothalamus, in order to realize the therapeutic effect on true precocious puberty.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Estrus ; drug effects ; Female ; Gene Expression ; drug effects ; Gonadotropin-Releasing Hormone ; genetics ; Hypothalamus ; drug effects ; metabolism ; Kisspeptins ; genetics ; Ovary ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; genetics ; Receptors, Kisspeptin-1 ; Reverse Transcriptase Polymerase Chain Reaction ; Sexual Maturation ; drug effects ; genetics ; Time Factors ; Uterus ; drug effects ; Vagina ; drug effects

OBJECTIVETo investigate the effects of different concentrations of lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), dexamethasone (Dex), and insulin on the mRNA and protein expressions of GPR54 in the MCF7 cell line in vitro.

METHODSMCF7 breasr cancer cells were cultured and treated with different concentrations of LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L). Those treated with culture fluid only served as controls. The mRNA and protein expressions of GPR54 were measured by real-time PCR and Western blot, respectively, after 6, 24, 48, and 72 hours of treatment.

RESULTSCompared with the blank con- trol, LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L) significantly increased the expressions of GPR54 mRNA (P < 0.05) and protein (P < 0.05).

CONCLUSIONLPS, TNFα, IL-6, Dex, and insulin evidently increase the expression of GPR54 in the MCF7 cell line, indicating their influence on the function of gonads by regulating the GPR54 level.

Blotting, Western ; Dexamethasone ; administration & dosage ; pharmacology ; Glucocorticoids ; administration & dosage ; pharmacology ; Gonads ; drug effects ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Insulin ; administration & dosage ; pharmacology ; Interleukin-6 ; administration & dosage ; pharmacology ; Lipopolysaccharides ; administration & dosage ; pharmacology ; MCF-7 Cells ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, G-Protein-Coupled ; drug effects ; genetics ; metabolism ; Receptors, Kisspeptin-1 ; Time Factors ; Tumor Necrosis Factor-alpha ; administration & dosage ; pharmacology