Form Of Luteinizing Hormone-releasing Hormone Research Articles

Bilateral Orchidectomy Revisited in Management of Metastatic Hormone-Sensitive Prostate Cancer.

Androgen deprivation therapy (ADT) is a well-established treatment for metastatic hormone-sensitive prostate cancer (mHSPC). It includes either bilateral orchiectomy or medical castration in form of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist. We conducted this study to compare surgical and medical castration in terms of time to progression (TTP) to castration resistant prostate cancer. Patients with mHSPC underwent either bilateral orchidectomy or medical castration by either LHRH agonist or by antagonist from November 2016 to May 2018 in our institution. Initial PSA and baseline imaging either magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET CT) finding were recorded. Serum PSA, testosterone, and FSH were repeated every 3months till 1year. All enrolled patients were followed up with a bone scan/MRI/ PET CT at 6months and 12months. End point of study was progression of disease and death of patient. Mean nadir PSA (ng/ml) after treatment was 4.7 and 9.8 in surgical and medical group respectively, whereas mean time to the nadir PSA was 8.7 and 8.8 respectively with no statistically significant difference. Mean TTP was 13.9months in bilateral orchidectomy group and 13.8months in medical castration group (chi-square 0.003, p value 0.958). There was no significant difference in time to progression between bilateral orchidectomy and medical castration. Considering nadir PSA level, better quality of life, patient compliance, reduced hospital visit, and decrease in cost of treatment, bilateral orchidectomy may be a better treatment option especially in developing countries.

Characteristics and management of erectile dysfunction after various treatments for prostate cancer

Preface Currently, there are many wellestablished therapeutic options for early prostate cancer, and therefore, it is difficult for both urologists and patients to choose the optimal treatment. It is essential for urologists to counsel their patients according to reliable information about the advantages and disadvantages of each therapeutic option. We picked the topic for this issue, “Characteristics and management of erectile dysfunction after various treatments for prostate cancer,” because erectile dysfunction (ED) is one of the most frequent adverse events encountered in the management of prostate cancer. We invited six specialists to review each therapeutic option: radical prostatectomy, laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, external beam radiotherapy, brachytherapy, and androgen deprivation therapy (ADT). Among these modalities, surgical interventions tend to induce a quick drop in erectile function with slow postoperative recovery. Early postoperative rehabilitation has been introduced, aiming at the early recovery of ED. On the contrary, radiation therapy tends to maintain the patient’s erectile function for a while after treatment but it gradually decreases. ADT may compromise not only the erectile function but also the libido level, and may result in significant deterioration of the patient’s quality of life. We hope these reviews will help urologists to counsel their patients with regards to decision-making in the management of early prostate cancer.

Is the metalloendopeptidase EC 3.4.24.15 (EP24.15), the enzyme that cleaves luteinizing hormone-releasing hormone (LHRH), an activating enzyme?

LHRH (GNRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive neuroendocrine axis comprising of the hypothalamus, pituitary and gonads. LHRH acts centrally through its initiation of pituitary gonadotrophin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of over 20 structural variants with a variety of roles in both the brain and peripheral tissues. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth and sixth bond of the decapeptide (Tyr(5)-Gly(6)) to form LHRH-(1-5). We have previously reported that the auto-regulation of LHRH-I (GNRH1) gene expression and secretion can also be mediated by itself and its processed peptide, LHRH-(1-5), centrally and in peripheral tissues. In this review, we present the evidence that EP24.15 is the main enzyme of LHRH metabolism. Following this, we look at the metabolism of other neuropeptides where an active peptide fragments is formed during degradation and use this as a platform to postulate that EP24.15 may also produce an active peptide fragment in the process of breaking down LHRH. We close this review by the role EP24.15 may have in regulation of the complex LHRH system.

Luteinizing Hormone-Releasing Hormone I (LHRH-I) and Its Metabolite in Peripheral Tissues

Luteinizing hormone-releasing hormone (LHRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive system through its initiation of pituitary gonadotropin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of many structural variants with a variety of roles in both the brain and peripheral tissues. Enormous interest has been focused on LHRH-I and LHRH-II and their cognate receptors as targets for designing therapies to treat cancers of the reproductive system. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth and sixth bond of the decapeptide (Tyr(5)-Gly(6)) to form LHRH-(1-5). We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its processed peptide, LHRH-(1-5). Furthermore, LHRH-(1-5) has also been shown to be involved in cell proliferation. This review will focus on the possible roles of LHRH and its processed peptide, LHRH-(1-5), in non-hypothalamic tissues.

Regulation of type II luteinizing hormone-releasing hormone (LHRH-II) gene expression by the processed peptide of LHRH-I, LHRH-(1-5) in endometrial cells.

Luteinizing hormone-releasing hormone (LHRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive system through its initiation of pituitary gonadotropin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of many structural variants with a variety of roles in both the brain and peripheral tissues. Enormous interest has been focused on LHRH-I, LHRH-II, and their cognate receptors as targets for designing therapies to treat cancers of the reproductive system. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the Tyr(5)-Gly(6) bond. We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its processed peptide, LHRH-(1-5). Given its importance in the brain, we have investigated the role of the specific processed peptide of LHRH-I, LHRH-(1-5), within Ishikawa cells, a human endometrial cell line. Using real-time polymerase chain reaction, we observed that LHRH-(1-5) upregulates LHRH-II mRNA expression in Ishikawa cells but does not exert any influence on LHRH-I mRNA levels. This is in contrast to the effects of LHRH-I, which affects the expression of LHRH-I mRNA. Our findings support a potential role for LHRH-(1-5) as a processed metabolite in the endometrium. Further investigations are needed to determine the role of this processed metabolite and to identify specific pathways involved in LHRH-(1-5) signaling.

A Novel Luteinizing Hormone Receptor Mutation in a Patient with Familial Male-Limited Precocious Puberty: Effect of the Size of a Critical Amino Acid on Receptor Activity

Familial male-limited precocious puberty (FMPP) is a form of luteinizing hormone-releasing hormone (LHRH)-independent isosexual precocious puberty caused by gain-of-function mutations of the luteinizing hormone/chorionic gonadotropin receptor (hLHR). The most common mutation is 1733 A>G, which causes substitution of Asp-578 by Gly. In this study, a male infant presented at the age of 20 months with accelerated sexual development was analyzed for the presence of activating mutations of the hLHR. Analysis of exon 11 of the hLHR gene by genomic polymerase chain reaction (PCR), asymmetric PCR, and dideoxy sequencing identified a single base substitution, 1734 T>A, which led to the replacement of Asp-578 by Glu. The same mutation was found in the mother. Expression of the mutated hLHR in HEK 293 cells demonstrated elevated basal levels of intracellular cAMP in the transfected cells confirming the constitutive activating nature of the mutated hLHR. A possible genotype-phenotype relationship of the hLHR mutations was examined by a comparison of thein vitroactivities of the hLHRs carrying the Asp578Gly, Asp578Tyr, Asp578Trp, and Asp578Glu mutations in HEK 293 cells. A positive correlation between the size of the substituting amino acid and the basal level of intracellular cAMP of cells expressing the mutated receptor was demonstrated.

LH-RH in the rat and mouse hypothalamus and rat hypophysial portal blood: confirmation of identity by high performance liquid chromatography

The nature of the immunoreactive (IR) form of luteinizing hormone-releasing hormone (LH-RH) in rat hypophysial portal vessel blood and in extracts of hypothalamus from rats and normal and hypogonadal ( hpg) mice was investigated using high performance liquid chromatography and two highly specific anti-LH-RH sera. In rat hypophysial portal blood and in hypothalamic extracts from rats and normal mice a single immunoreactive peak was present which corresponded in retention time to synthetic LH-RH. No LH-RH-IR was detected in hypothalamic extracts from the hpg strain of mouse.

Two chemically and immunologically distinct forms of luteinizing hormone-releasing hormone are differentially expressed in frog neural tissues

Immunoreactive luteinizing hormone-releasing hormone (IR-LRF) has been measured in several neural tissues of the frog Rana catesbeiana and characterized by bioassay, chromatography and immunological analysis. Frog brain contains the mammalian form of LRF (mLRF), whereas, sympathetic ganglia and adrenal glands contain a form of LRF (pLRF) chromatographically and immunologically similar to the IR-LRF found in the central nervous systems of several piscine species. Frog retina contains both mLRF and pLRF, in a ratio of about 1:2. The two forms of LRF are apparently equipotent in their ability to release LH from rat gonadotrophs in vitro. Immunological analysis of the pLRF found in the frog nervous system suggests that it is a decapeptide, like mLRF, with one or more amino acid substitutions in the mLRF molecule.