Animals ; Diethylhexyl Phthalate ; toxicity ; Female ; Ovary ; drug effects ; metabolism ; ultrastructure ; Rats, Sprague-Dawley ; Receptors, LH ; metabolism ; Receptors, LHRH ; metabolism ; Toxicity Tests

Methylphenidate (MPH) is the most preferred drug for treatment of the attention deficit hyperactivity disorder (ADHD). Here, we aimed to discuss the possible effects and mechanisms of MPH on precocious puberty (PP) via a case series with seven children who had normal body mass index. In this case series we evaluated seven children with ADHD, who had received MPH for at least 6 months (0.5 mg/kg/dose three times a day, maximum 60 mg) and admitted to Department of Pediatric Endocrinology with PP symptoms. The mean age was 8.16 years. Basal hormonal levels (luteinizing hormone [LH], follicle stimulating hormone, and estrogen/testosterone) were within normal range. Results of LH-releasing hormone stimulation tests demonstrated central pubertal responses. Glutamine, dopamine and noradrenaline are most important excitatory neurotransmitters that have a role at the beginning of puberty. The effect of MPH, cumulating dopamine and noradrenaline in the synaptic gap could be associated with the acceleration of puberty with the excitatory effect of dopamine’s gonadotropin-releasing hormone (GnRH) release, excitatory effect of noradrenaline’s GnRH release and the disappearance of GnRH receptor expression suppressor effect on prolactin disinhibitory effect.
Acceleration ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; Body Mass Index ; Child ; Dopamine ; Endocrinology ; Follicle Stimulating Hormone ; Glutamine ; Gonadotropin-Releasing Hormone ; Humans ; Methylphenidate ; Neurotransmitter Agents ; Norepinephrine ; Prolactin ; Puberty ; Puberty, Precocious ; Receptors, LHRH ; Reference Values

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl^-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl^-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.
Aged ; Androgen Antagonists/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Cholesterol/blood* ; Drug Therapy, Combination ; Humans ; Leuprolide/therapeutic use* ; Male ; Middle Aged ; Prostatic Neoplasms/pathology* ; Quality of Life ; Receptors, LHRH/agonists* ; Republic of Korea ; Testosterone/blood* ; Treatment Outcome ; Triglycerides/blood*

Uterine fibroids (leiomyomas or myomas), benign monoclonal tumors, are the most common benign tumors in women. Heavy or prolonged menstrual bleeding, abnormal uterine bleeding, resultant anemia, pelvic pain, infertility, and/or recurrent pregnancy loss are generally associated with uterine fibroids. Although curative treatment of this tumor relies on surgical therapies, medical treatments are considered the first-line treatment to preserve fertility and avoid or delay surgery. The aim of this review is to provide available and emerging medical treatment options for symptomatic uterine fibroids. Literature review and consensus of expert opinion. Many uterine fibroids are asymptomatic and require no intervention, although it is advisable to follow-up patients to document stability in size and growth. Fibroid-associated symptoms include heavy menstrual bleeding and pain or pelvic discomfort. The association between infertility and fibroids increases with age. Treatment options for symptomatic uterine fibroids — include medical, surgical, and radiologically guided interventions. Various medical therapies are now available for women with uterine fibroids, although each therapy has its own advantages and disadvantages. Currently, gonadotrophin-releasing hormone (GnRH) agonists and selective progesterone receptor modulators (SPRMs) are the most effective medical therapies, with the most evidence to support their reduction of fibroid volume and symptomatic improvement in menstrual bleeding. The choice of treatment depends on the patient's personal treatment goals, as well as efficacy and need for repeated interventions.
Anemia ; Consensus ; Expert Testimony ; Female ; Fertility ; Follow-Up Studies ; Hemorrhage ; Humans ; Infertility ; Leiomyoma* ; Pelvic Pain ; Pregnancy ; Receptors, LHRH ; Receptors, Progesterone ; Uterine Hemorrhage

Base Sequence ; Child, Preschool ; Humans ; Male ; Point Mutation ; Polymerase Chain Reaction ; Puberty, Precocious ; genetics ; Receptors, LHRH ; genetics ; Sequence Analysis, DNA ; Testosterone ; blood

This study is to investigate the anti-tumor effect in vitro of methotrexate modified by LH-RH peptide (LH-RH-MTX). LH-RH receptors highly expressing MCF-7 human breast carcinoma cell line and lowly expressing K562 human erythroleukemia cell line were served as the tested cells. The cell proliferation inhibition rates of LH-RH-MTX were detected by MTT colorimetric assay. The effects of LH-RH-MTX on the cell cycle and apoptosis rates were detected by flow cytometry. The inhibition rate of LH-RH-MTX on MCF-7 cells was much higher than that on K562 cells, and the inhibition rate of LH-RH-MTX on MCF-7 cells was much higher than that of free MTX at the same concentration. The inhibition rate of LH-RH-MTX on rat bone marrow mononuclear cells was less than that of free MTX. The number of MCF-7 cells in S phase increased after administration of LH-RH-MTX. The apoptosis rate of LH-RH-MTX group significantly increased compared with that of the control group and MTX group. The relative expression of LHRHR mRNA of LH-RH-MTX group markedly decreased compared with that of the control group and MTX group. LH-RH-MTX is realizable to reduce drug side effects, increase the therapeutic index and achieve tumor-targeted therapy.
Animals ; Antimetabolites, Antineoplastic ; chemical synthesis ; pharmacology ; Apoptosis ; drug effects ; Bone Marrow Cells ; cytology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drug Delivery Systems ; Gonadotropin-Releasing Hormone ; chemistry ; pharmacology ; Humans ; K562 Cells ; Leukocytes, Mononuclear ; MCF-7 Cells ; Methotrexate ; chemical synthesis ; pharmacology ; RNA, Messenger ; metabolism ; Rats ; Receptors, LHRH ; biosynthesis ; genetics

Recently various peptide receptors which displayed the highest binding affinity and specificity with their peptide ligands by ligand-receptor have been exploited to develop drug delivery system which can directionally deliver drug to targeted cell. It is significant to study and applicate, including targeted drug delivery system mediated by bombesin receptor, somatostatin receptor, SynB3 receptor, LH-RH receptor and other peptide receptor, et al. Several small peptide fragments were selected as carriers radicals combining doxorubicin, 2-pyrrolino-DOX, methotrexate, cis-platinum, and camptothecin to form hybrid cytotoxic analogs. These highly potent cytotoxic analogs have been designed as targeted anti-tumor agents for the treatment and study of various cancers that possess receptors for the carrier peptide.
Animals ; Antineoplastic Agents ; therapeutic use ; Doxorubicin ; analogs & derivatives ; therapeutic use ; Drug Delivery Systems ; Humans ; Neoplasms ; drug therapy ; metabolism ; Oligopeptides ; metabolism ; Pyrroles ; therapeutic use ; Receptors, Bombesin ; metabolism ; Receptors, LHRH ; metabolism ; Receptors, Somatostatin ; metabolism

PURPOSE: To confirm the production of extra-hypothalamic gonadotropin releasing hormone (GnRH) and GnRH receptor in bladder mucosal epithelia, and a potential role of GnRH on the bladder, normal human bladder tissues, and primary cultured dog bladder mucosal epithelia were studied. MATERIALS AND METHODS: For this study, normal human bladder tissue from 4 patients and primary cultured normal bladder mucosal epithelial cells from 2 dogs were used. For localization of extra-hypothalamic GnRH and the extra-pituitary GnRH receptor, in situ hybridization and immunohistochemical staining were done. To evaluate the roles of exogenous GnRH in bladder mucosal cells, the culture media were supplemented with charcoal stripped serum and 4 different concentrations of GnRH (0, 10(-3), 10(-5) and 10(-7)M). The effect of exogenous GnRH was evaluated using a hemocytometer and fluorescence activated cell sorter (FACS). RESULTS: GnRH and GnRH receptors, and their mRNA signals were localized in most of the both human bladder mucosal epithelia and dog bladder mucosal epithelia, but not in a few cells. There were no significant GnRH effects on cellular proliferation and cell cycle changes (p<0.05). CONCLISIONS: Bladder mucosal epithelium produces GnRH and GnRH receptors, but they do not effect either the proliferation or cell cycle changes. Although the exact function of extra-hypothalamic bladder GnRH is unknown, GnRH and GnRH receptors would be assumed to have unknown autocrine or paracrine relationships with each other.
Animals ; Cell Cycle ; Cell Proliferation ; Charcoal ; Culture Media ; Dogs ; Epithelial Cells ; Epithelium ; Fluorescence ; Gonadotropin-Releasing Hormone* ; Gonadotropins* ; Humans ; In Situ Hybridization ; Mucous Membrane ; Receptors, LHRH* ; RNA, Messenger ; Urinary Bladder*

OBJECTIVETo investigate ovarian follicular damage induced by chemotherapeutic agents and gonadotropin- releasing hormone receptor (GnRHR) expression in the damaged ovaries in rats.

METHODSTwo groups of adult SD rats were subjected to intraperitoneal injection of a single-dose cyclophosphamide and saline, respectively, and 8 weeks later, the ovaries were taken for observing the ovarian damages. The distribution of GnRHR was detected with immunohistochemistry, and RT-PCR was used to determine the expression of GnRHR mRNA in the rat ovaries.

RESULTSMassive primordial follicular loss occurred in the ovaries of rats exposed to cyclophosphamide with also evident stromal ovarian blood vessel damages and focal fibrosis. Both the protein and mRNA expressions of GnRHR were detected in normal rat ovaries, but in rats exposed to cyclophosphamide, the expressions were significantly lowered in the ovaries (P<0.05).

CONCLUSIONLow-level GnRHR expressions in the ovaries of rats with cyclophosphamide exposure suggest microenvironment disturbances in the damaged rat ovaries in advanced stage of chemotherapy.

Animals ; Cyclophosphamide ; adverse effects ; Female ; Humans ; Ovary ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptors, LHRH ; metabolism

Isolated gonadotropin deficiency can be idiopathic or a part of X-linked Kallmann syndrome associated with anosmia. There have been several trials to reveal the genetic mutations that affect gonadotropin secretion, and approximately 10% of sporadic patients have mutations in either gonadotropin releasing hormone receptor (GnRHR) or KAL1 gene. Here we report one familial cases of idiopathic hypogonadotropic hypogonadism occurred in a boy and his elder sister. They presented with delayed puberty and hypoplastic gonads, but normal sense of smell. We performed GnRHR and KAL1 mutation analysis, but could not find any mutation.
Gonadotropins ; Gonads ; Humans ; Hypogonadism* ; Kallmann Syndrome ; Male* ; Olfaction Disorders ; Puberty, Delayed ; Receptors, LHRH ; Siblings* ; Smell