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At least 19 recordsLinked to original sources
PubMed2006

Immunocytogenetic effects of gonadotropin releasing hormone analogue: Triptorelin Pamoate (Decapeptyl) during in vitro fertilization treatment.

In this study, the immunocytogenetic effects of Decapeptyl (Triptorelin Pamoate) were assessed in the peripheral blood lymphocytes of females undergoing in vitro fertilization (IVF) treatment. Blood samples were taken from 34 females (23 treated and 11 controls), cultured and examined for sister chromatid exchanges (SCE) and cell replication index (CRI). The SCE frequency increased around ovulation time in the controls, and around the time of human chorionic gonadotropin administration in the IVF group. However, the SCE rate was significantly higher in the latter group. Furthermore, the white blood cells (WBC) count was significantly higher on the day of ovum pick up compared to the day preceding luteinizing hormone (LH) and follicle stimulating hormone (FSH) treatment. Similar observations were recorded with respect to phagocytic activity tested by nitroblue tetrazolium (NBT) assay. The nitric oxide production abilities of macrophages were not significantly changed in the LH, FSH-treated group relative to its control. Finally, the 50% complement hemolytic activity (CH50) assay results indicated that Decapeptyl lacks a significant potential to affect the complement system.

Adult↗
PubMed2003

Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer.

OBJECTIVE: To compare the efficacy of monthly administrations of the luteinizing hormone-releasing hormone agonists triptorelin pamoate and leuprolide acetate to induce and maintain castrate levels of serum testosterone in men with advanced prostate cancer. PATIENTS AND METHODS: Men with advanced prostate cancer were randomly assigned to receive triptorelin 3.75 mg or leuprolide 7.5 mg. The agent was injected intramuscularly every 28 days for nine injections. Primary endpoints were the percentages of men whose serum testosterone concentrations declined to and were maintained at or below castrate levels (</= 1.735 nmol/L or </= 500 ng/L) during 9 months (253 days) of treatment. Secondary endpoints were luteinizing hormone levels, bone pain, prostate specific antigen levels, quality of life, testosterone pharmacodynamics, survival, and safety variables. RESULTS: In all, 284 men received either triptorelin (140) or leuprolide (144). The percentage of men with castrate levels of serum testosterone was lower at 29 days for triptorelin than for leuprolide (91.2% vs 99.3%; point estimate - 8.0, 95% confidence interval - 16.9% to - 1.4%), but equivalent at 57 days (97.7% vs 97.1%). The mean (98.8% vs 97.3%) and cumulative (96.2% vs 91.2%) castration maintenance rates between 29 and 253 days were equivalent between the treatment groups. Secondary endpoints were equivalent between treatment groups except for the 9-month survival rate, which was significantly higher for triptorelin than for leuprolide (97.0% vs 90.5%; P = 0.033). Both treatments were well tolerated. CONCLUSION: Triptorelin reduced testosterone concentrations less rapidly, but maintained castration as effectively as leuprolide. There was no evidence that the slower onset of castration caused deleterious effects.

Aged↗
PubMed2003

Oxytocin receptor is expressed in the penis and mediates an estrogen-dependent smooth muscle contractility.

Oxytocin (OT) is released by the posterior pituitary during male orgasm and is supposed to participate in the ejaculatory process. We now report evidence demonstrating the presence of an OT receptor gene (real-time RT-PCR and Northern blot) and protein (immunohistochemistry, Western blot, and binding studies) expression in the rabbit and human corpus cavernosum (CC) and its possible involvement in postorgasmic penile detumescence. OT receptor is expressed in the penis at a concentration similar to that present in other portions of the male genital tract and mediates CC contractility. OT-induced CC contractility is clearly regulated by the changing sex steroid milieu. In fact, we found that in a rabbit model of hypogonadotropic hypogonadism (induced by a single administration of the long-acting GnRH agonist triptorelin pamoate, 2.9 mg/kg), OT responsiveness was strongly reduced and was completely restored by estradiol valerate (3.3 mg/kg weekly), but not by testosterone enanthate (30 mg/kg weekly). As we found that CC expresses both subtypes of estrogen receptors and P450 aromatase, we hypothesized a physiological role for endogenous estrogens in regulating OT responsiveness. We therefore treated adult rabbits with an aromatase inhibitor (letrozole, 2.5 mg/kg) or an antiestrogen (tamoxifen, 0.25 mg/kg) for 3 wk. Both treatments significantly reduced CC responsiveness to OT stimulation. In conclusion, these findings indicate that OT might participate in inducing postorgasmic penile flaccidity and suggest a new role for estrogens in the male: regulation of CC responsiveness to OT.

Animals↗
PubMed2003

Eligard: leuprolide acetate in a novel sustained-release delivery system.

Androgen deprivation as a treatment for prostate cancer has evolved since the pioneering studies of Huggins and Hodges 60 years ago using surgical castration or estrogen treatments. The most common hormonal treatments today use injections of luteinizing hormone-releasing hormone (LHRH) agonists. The US Food and Drug Administration (FDA) has approved 5 LHRH agonist formulations for treatment of prostate cancer in the United States. Of these approved products, 3 involve different delivery systems for the LHRH superagonist leuprolide acetate. Sustained-release formulations of 2 distinct LHRH agonists, goserelin acetate and triptorelin pamoate, are also commercially available. This review focuses on new data on a novel formulation of leuprolide acetate (Eligard; Atrix Laboratories Inc., Fort Collins, CO) that incorporates a unique mixture of selected polymers and solvents to achieve sustained drug delivery after subcutaneous injection. The FDA has approved 1-month and 3-month formulations of Eligard, and 4-month and 6-month products are in development. In clinical trials, Eligard achieves reliable and sustained suppression of serum testosterone to castration levels (< or =50 ng/dL). Of the patients treated with the 1-month and 3-month formulations, 98% (115 of 117) and 94% (104 of 111), respectively, reached testosterone levels of < or =20 ng/dL. Breakthroughs, defined as testosterone levels >50 ng/dL after achievement of castration levels, occurred rarely at 0% (0 of 117) for the 1-month and at 0.9% (1 of 111) for the 3-month formulations in patients receiving Eligard. The degree of disease control and the adverse-events profile are commensurate with the effectiveness of the testosterone suppression; the incidence of severe hot flashes is actually lower than anticipated. Additional studies with these novel formulations are warranted.

Antineoplastic Agents, Hormonal↗
PubMed2006

Combined use of growth hormone and gonadotropin-releasing hormone analogue in short normal adolescent girls: a survey from Iran.

Combined therapy with gonadotropin-releasing hormone (GnRH) analogue and growth hormone (GH) has been used to increase the height of adolescents who are not GH deficient and who have normally timed puberty. Its use, however, is still controversial. For 2 years simultaneously, we treated eight healthy girls with very low predicted adult height (PAH < 145 cm) who were entering into normally timed puberty. The GnRH analogue triptorelin pamoate (Decapeptyl, 100 microg/kg intramuscularly every 4 weeks) and GH (0.1 IU/kg/day subcutaneously, 6 days/week) were administered. The mean chronologic age (CA) of our patients was 11.01 +/- 0.95 years, and mean bone age (BA) was 12.25 +/- 1.13 years. With a height of 131.50 +/- 5.83 cm (-2.37 +/- 0.35 SD below the mean) and PAH of 140.87 +/- 3.53 cm, they were all in Tanner stage 2-3 of puberty (except one patient in stage 4). In all cases, GH and thyroid hormone deficiency were ruled out before the study began. Height and BA were measured immediately after discontinuation of therapy. PAH was determined before and at the end of therapy. Combined treatment resulted in a 4.13 +/- 1.19 cm increase in PAH (p < 0.01). Height increased significantly to 142.66 +/- 3.54 cm at the end of treatment (p < 0.01). Height standard deviation score for CA increased from -2.37 +/- 0.35 to -2.32 +/- 0.67, showing no significant improvement (p = 0.5). Height age (HA)/BA ratio and BA/CA ratio both demonstrated significant growth during the treatment (p < 0.03 and p < 0.01, respectively), whereas HA/CA ratio did not improve significantly (p < 0.32). During treatment, puberty was completely suppressed in all cases. Combination therapy with GnRH analogue and GH resulted in significant improvement in height and PAH during therapy. Additional, and perhaps more long-term, studies are required to show whether this kind of treatment is effective in improving final adult height. The cost-benefit of such therapies should also be taken into account.

Body Height↗
PubMed2001

A phase II trial with new triptorelin sustained release formulations in prostatic carcinoma.

OBJECTIVES: The objectives were to assess if a single intramuscular (i.m.) injection of the GnRH agonist triptorelin, as pamoate Sustained Release (RS) 11.25 mg, was able to induce pharmacological castration and to maintain the plasma testosterone levels in the castrate range (< 1.735 nmol/l) up to 3 months in prostatic carcinoma. METHODS: Two different formulations of triptorelin pamoate 11.25 mg were assessed in 2 groups of 10 patients suffering from prostatic carcinoma. Each patient received one i.m. injection of triptorelin pamoate SR 11.25 mg. Triptorelin and testosterone levels were measured over 3 months. Pain, micturition difficulties, performance status, local and general tolerance, and the occurrence of adverse events were evaluated. RESULTS: Both formulations were able to induce castration levels (<1.735 nmol/l) of testosterone within 3 to 4 weeks post-injection, and to maintain levels below 1.735 nmol/l till the end of 3rd month. The bioavailability of one formulation (DLGSD-3-95-21) tended to be greater. This may explain the quicker onset of castration and the slight better maintenance of low testosterone levels during the 3rd month observed with this formulation. In terms of clinical end-points, the local tolerance of both formulations was excellent. No serious adverse events were recorded except transient hot flushes in 2 cases and slight bone pain in one. CONCLUSION: Triptorelin pamoate 11.25 mg given in microgranules is a 3-month sustained-release administration form which appears to be safe and effective in advanced prostatic carcinoma. Based on the findings of this study, the formulation with greater bioavailability (DLGSD-3-95-21) was selected as formulation of choice to be used for clinical treatments and further clinical investigation.

Aged↗
PubMed2002

Effects of long-term treatment with the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl and the LHRH antagonist Cetrorelix on the levels of pituitary LHRH receptors and their mRNA expression in rats.

The effects of depot formulations of the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl (25 microg/day) for 30 days or LHRH antagonist Cetrorelix pamoate (100 microg/day) for 30 days and daily injections of 100 microg of Decapeptyl for 10 days on the expression of mRNA for pituitary LHRH receptor (LHRH-R) and the levels of LHRH-R protein were evaluated in rats. Serum sex steroid concentrations and the weights of the reproductive organs were greatly reduced in all groups treated with analogs, demonstrating an efficient blockade of the pituitary-gonadal axis. Decapeptyl microcapsules elevated serum LH in female rats, but decreased it in male rats. LHRH-R mRNA expression in female pituitaries was reduced to 41% and 56-65% on days 10 and 30, respectively, whereas LHRH-R protein was 64% of control on day 10 and returned to pretreatment levels on day 30. Decapeptyl microcapsules reduced LHRH-R mRNA expression in male pituitaries to 58% on day 30 but not LHRH-R protein. Daily injections of Decapeptyl caused a desensitization of LH responses in female rats, while raising LHRH-R mRNA expression in female rats by 23% and LHRH-R protein levels by 119%. Cetrorelix pamoate reduced serum LH in female rats and diminished LHRH-R mRNA to 30% and 26% and LHRH-R protein to 57% and 48% on days 10 and 30, respectively. Elevated LHRH-R protein levels of ovariectomized rats were reduced after 10-day treatment with Cetrorelix or 100 microg/day Decapeptyl. Thus, changes in the mRNA expression after treatment with Cetrorelix, but not always Decapeptyl, paralleled those of LHRH-R protein. The inhibitory effect of Cetrorelix on serum LH, pituitary LHRH-R mRNA, and LHRH-R protein was greater than that of Decapeptyl.

Animals↗
PubMed1985

Precocious puberty associated with neurofibromatosis and optic gliomas. Treatment with luteinizing hormone releasing hormone analogue.

Seven children with central precocious puberty and either neurofibromatosis and/or optic gliomas were referred to the National Institutes of Health, Bethesda, Md, for evaluation and treatment with the long-acting luteinizing hormone releasing hormone analogue (LHRHa) D-Trp6-Pro9-NEt-LHRH. Only six of the seven children chose to receive treatment. Four children presented with neurofibromatosis, three of whom also had optic gliomas; the remaining three children had isolated optic gliomas, without other neurocutaneous stigmas. All had central precocious puberty mediated by activation of the hypothalamic-pituitary-gonadal axis. Six months of LHRHa therapy caused suppression of gonadotropin and sex steroid levels, stabilization or regression of secondary sexual characteristics, and decreases in growth velocity and the rate of bone age maturation. We conclude that LHRHa therapy is effective in the treatment of central precocious puberty secondary to neurofibromatosis and/or optic gliomas.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Novel concept of antisurvival factor (ASF) therapy produces an objective clinical response in four patients with hormone-refractory prostate cancer: case report.

BACKGROUND: Osteoblasts and osteoblast-derived survival growth factors, such as insulin-like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate cancer cells, thereby producing cytotoxic drug-resistant tumor growth, in vitro. METHODS: We tested a novel therapeutic approach, referred to as antisurvival factor (AFS) therapy, that aimed at reduction of osteoblast-derived IGFs, using dexamethasone (4 mg per os, qD) and growth hormone (GH)-dependent liver-derived IGFs, using a somatostatin-analog (lanreotide, 30 mg, intramuscularly (i.m.), q14D) in combination with triptorelin (3.75 mg, intramuscularly, q28D) to produce a clinical response in 4 patients with progressing hormone-refractory prostate cancer. RESULTS: The patients given ASF therapy exhibited an excellent improvement of clinical performance and a decline of prostate-specific antigen (PSA) within 2 months of ASF therapy. One of them experienced excellent clinical response (normalization of PSA), two experienced good clinical response (decline of PSA of more than 50%), and one experienced stabilization (decline of PSA of less than 50%). CONCLUSIONS: We conclude that this novel concept of combination therapy, using ASF with hormone ablation, is a promising salvage therapy that should be further assessed with a randomized clinical trial.

Aged↗
PubMed1996

Luteinizing hormone-releasing hormone agonist triptorelin in combination with cytotoxic chemotherapy in patients with advanced ovarian carcinoma. A prospective double blind randomized trial. Decapeptyl Ovarian Cancer Study Group.

BACKGROUND: Several lines of evidence suggest that the proliferation of ovarian carcinoma might be stimulated by gonadotrophins. A number of Phase I/Phase II clinical trials have reported that the suppression of endogenous luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone (LHRH) analogs induced objective remissions and/or disease stabilization in 10-30% of patients with advanced refractory ovarian carcinoma. The current study was performed to evaluate whether the addition of LHRH agonist treatment to standard platinum-based chemotherapy could prolong survival of patients with surgically treated Stage III or IV epithelial ovarian carcinoma. METHODS: One hundred and thirty-five patients with Stage III or IV epithelial ovarian carcinoma participated in this prospective randomized double blind trial. After cytoreductive surgery, 69 patients received monthly injections of a depot preparation of the LHRH agonist [D-Trp6] LHRH (triptorelin, 3.75 mg) and 66 patients received placebo until their deaths or termination of trial, respectively. All patients were treated with a standard platinum-based chemotherapy, and, if necessary, with second- or third-line cytotoxic regimens. RESULTS: Endogenous gonadotrophins were reliably suppressed in patients treated with triptorelin. However, their progression free and overall survival were not significantly different from that of patients receiving placebo injections (statistical power > 80% for a difference between both groups of > or = 20%). CONCLUSIONS: The results of this trial suggest that the suppression of endogenous gonadotrophins by conventional doses of an LHRH agonist produces no relevant beneficial effects in patients with advanced ovarian carcinoma who receive standard surgical cytoreduction and cytotoxic chemotherapy.

Adult↗
PubMed1988

Two partial remissions induced by an LHRH analogue in two postmenopausal women with metastatic breast cancer.

We report two cases of metastatic breast cancer occurring in two postmenopausal women. Treatment with a luteinizing hormone-releasing hormone (LHRH) analogue, D-TRP6-LHRH, induced partial remission. The blood levels of the follicle stimulating hormone (FSH) and luteinizing hormone (LH) fell sharply under treatment, but the levels of estradiol, estriol, and estrone did not change significantly. We also described the putative mechanisms of action of the LHRH analog.

Aged↗
PubMed1990

Inhibitory effects of analogs of luteinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events that accompany tumor regression.

Syrian golden hamsters bearing N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas were treated for 2 months with the delayed delivery systems of the agonist D-Trp-6-LH-RH (microcapsules releasing 25 micrograms/day for 30 days), the somatostatin analog RC-160 (the microcapsules liberating 48.2 micrograms/day for 30 days), or with the combination of these two analogues. The increase in the dose of RC-160 was possible in view of the lack of toxicity of this analog. This higher dose of RC-160 exerted a greater suppressive effect on pancreatic cancers than the regimens previously used (5-25 micrograms/day). RC-160, D-Trp-6-LH-RH, and their combination reduced the number of pancreatic carcinomas and significantly inhibited tumor growth as compared with the controls. The combination had the strongest tumor-inhibitory effect and reduced tumor weight by 85% as compared with controls. Both the light and electron microscopic analysis of the tumors showed that the inhibitory effect was due to the enhancement of apoptosis (programmed cell death) of tumor cells. Insulin-like growth factor (IGF-I) receptors were detected immunohistochemically in the untreated tumors and their number decreased after the treatment with the analogues. Binding of D-Trp-6-LH-RH and RC-160 to tumor cells was shown immunohistochemically and receptors to these analogues and IGF-I were also determined biochemically by radioligand titration. Treatment with D-Trp-6-LH-RH and RC-160 decreased the binding capacity of receptors for D-Trp-6-LH-RH and IGF-I, producing down-regulation of these receptors. This suggests that pancreatic tumor cells with receptors to these peptides are sensitive to the treatment. This work reinforces the view that the combination of high doses of somatostatin analog RC-160 with LH-RH agonists or antagonists should be considered for the development of a new hormonal therapy for ductal pancreatic cancers.

Amino Acid Sequence↗
PubMed2002

A study of the binding between polymers and peptides, using affinity capillary electrophoresis, applied to polymeric drug delivery systems.

We have investigated the potential of affinity capillary electrophoresis (ACE) to evaluate binding constants between an anionic polydispersed polymer and four peptides. Nonlinear regression and three current linearization methods, the y-reciprocal, the x-reciprocal and the double-reciprocal, were employed for the estimation of the binding constants. The x-reciprocal and the double-reciprocal plots indicated the presence of two portions of straight lines for angiopeptin, triptorelin and the thyrotropin releasing hormone (TRH), and therefore the probable existence of a second-order interaction which causes the deviation from the 1:1 model. Peptide 1 exhibited a unique binding constant of 2.4 x 10(6)M(-1). In contrast, angiopeptin, triptorelin and TRH exhibited a K(1) of 4.0 x 10(6), 5.3 x 10(6) and 20.2 x 10(6)M(-1), respectively, and a K(2) of 0.4 x 10(6), 0.5 x 10(6) and 1.4 x 10(6)M(-1), respectively. The origin of the high scattering of the data points was further investigated. Neither the viscosity, nor the adsorption of the peptides to the capillary wall appeared to be the determining factor of data scattering. Finally, a possible adsorption of the polymer leading to the electroosmotic flow instability was supposed.

Drug Carriers↗
PubMed1988

An efficient algorithm for sequencing peptides using fast atom bombardment mass spectral data.

An efficient algorithm is described for sequencing peptides from sequence ions appearing in fast atom bombardment (FAB) and FAB tandem mass spectra. The following features are incorporated in the algorithm. The members of the set of sequence ions are represented by all possible combinations of N- and C-terminal fragment ions. From the known N- and C-terminating groups and molecular weight (MW) of the peptide, the sequence ions are mathematically re-expressed as N-terminal residue ions and arranged in ascending order. The peptide sequence is computed, in a stepwise iterative procedure, from the mass differences between the mathematically re-expressed N-terminal residue ions and the predicted peptide subsequences for the neighboring ions of lower mass. These mass differences correspond to combinations of known amino acid residues which have previously been computed and tabulated, based upon the FAB fragmentation rules for peptides. The algorithm was successfully applied to sequence the following peptides from their respective FAB or FAB tandem mass spectrum: decapeptyl (MW 1310), angiotensin II (MW 1045), and two 'unknown' peptides (MW 1227 and 1485, respectively). Two criteria used to predict the correct peptide sequence from among many possibilities are the minimum number of amino acid residues and the maximum fragmentation probability per amino acid residue.

Algorithms↗
PubMed2006

Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate.

BACKGROUND: Menorrhagia is a serious complication in young female oncology patients who suffer from severe thrombocytopenia during myelosuppressive treatment. To the authors' knowledge, little is known regarding the incidence of this complication or the effectiveness of possible therapies for its prevention. METHODS: In this retrospective clinical study, after a thorough gynecologic evaluation, young female oncology patients with regular menstrual cycles undergoing myelosuppressive treatments received either depo-medroxyprogesterone acetate (DMPA), or D-tryptophan-6-luteinizing hormone-releasing hormone depot treatment (gonadotropin-releasing hormone agonist [GnRH-a]), or no treatment before the administration of myelosuppresive chemotherapy. Only patients who later developed severe thrombocytopenia (<25,000 platelets per muL) were included in the study. Daily blood counts, menorrhagia, nonvaginal bleeding episodes, and the need for blood products, gynecologic consultations, and other medical interventions were determined. RESULTS: Of 101 women with cancer who met the inclusion criteria, 42 patients received DMPA, 39 patients received GnRH-a, and 20 patients remained untreated. The mean duration (+/- standard deviation) of severe thrombocytopenia was 24.76 +/- 23.6 days. Four patients were not included because of significant gynecologic pathologies. General bleeding from nongynecologic sites was similar for all groups and was not associated with vaginal bleeding. Severe or moderate menorrhagia was documented in none of the 39 women who received GnRH-a, in 9 patients (21.4%) who received DMPA, and in 9 untreated patients (40%; P = .02). Fewer calls for urgent gynecologic consultations were documented in the GnRH-a group compared with the untreated group (P < .0001). CONCLUSIONS: Female patients undergoing myelosupressive therapy are at high risk of developing significant menorrhagia during prolonged, severe thrombocytopenia. Pretreatment gynecologic evaluation can detect significant pelvic pathologies. GnRH-a treatment effectively prevented menorrhagia, whereas DMPA administration was less effective.

Adolescent↗
PubMed1989

Effect of D-tryptophan-6-luteinizing hormone-releasing hormone on the tumoral growth and plasma sex steroid levels in cirrhotic patients with hepatocellular carcinoma.

Certain evidence suggests androgen dependence of hepatocellular carcinoma in cirrhotic patients. Consequently, it was postulated that antiandrogen therapy might be effective in the treatment of hepatocellular carcinoma. D-Tryptophan-6-luteinizing hormone-releasing hormone is a potent agonist analog of luteinizing hormone-releasing hormone which, when chronically administered, inhibits the pituitary gonadal axis and testicular androgen secretion in man. We studied the effects of D-tryptophan-6-luteinizing hormone-releasing hormone on tumoral growth in 17 male cirrhotic patients with hepatocellular carcinoma. After 3 to 6 months of therapy, no tumoral response was observed. Furthermore, measurements of plasma levels of testosterone, dihydrotestosterone, androstenedione, estradiol, estrone and sex hormone-binding globulin were performed before and 3 months after initiation of the antiandrogenic treatment. Before treatment, hypoandrogenism and hyperestrogenism were present; D-tryptophan-6-luteinizing hormone-releasing hormone induced a fall in plasma testosterone and dihydrotestosterone levels. Only a moderate decrease in estradiol and no modification of plasma estrone and sex hormone-binding globulin were found, indicating that the hyperestrogenemia of cirrhotic patients could be attributed to an increase in peripheral aromatization of androgens of adrenal origin. The inability of D-tryptophan-6-luteinizing hormone-releasing hormone to reduce the growth of hepatocellular carcinoma is not totally in disagreement with the concept of androgen dependence of hepatocellular carcinoma since D-tryptophan-6-luteinizing hormone-releasing hormone does not inhibit the production of androgens of adrenal origin.

Aged↗
PubMed2002

Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells.

The purpose of this study was to investigate the effects of a potent LHRH agonist, [D-Trp(6)]LHRH on the basal and EGF-induced cell proliferation and the metastasis-associated properties in A431 human epidermoid carcinoma. [D-Trp(6)]LHRH time-dependently inhibited the basal and EGF-stimulated growth of A431 cancer cells. It is assumed that phosphorylation/dephosphorylation of cellular proteins is highly related to cell growth. This study demonstrates that [D-Trp(6)]LHRH decreased the basal and EGF-induced total cellular kinase activity, particularly the tyrosine phosphorylation of several cellular proteins including the EGFR. In contrast, [D-Trp(6)]LHRH did not cause detectable changes in basal and EGF-stimulated serine/threonine phosphorylation of A431 cellular proteins. The inhibitory effect of [D-Trp(6)]LHRH on A431 cell proliferation was associated with apoptosis as evidenced by the cell morphology and DNA integrity (ladder pattern), the expression of interleukin 1beta-converting enzyme (ICE) and activation of caspase. Furthermore, EGF could rescue the remaining attached A431 cells following [D-Trp(6)]LHRH treatment for 48 hr, which suggests that limited exposure to [D-Trp(6)]LHRH did not channel all cells to irreversible apoptotic process. We also determined the effects of [D-Trp(6)]LHRH on metastasis-associated properties in A431 cells. [D-Trp(6)]LHRH reduced both basal and EGF-stimulated secretion of MMP-9 and MMP-2. In addition, [D-Trp(6)]LHRH suppressed the basal and EGF-induced invasive activity of A431 cells based on an in vitro invasion assay. In conclusion, this study indicates that [D-Trp(6)]LHRH may act partly through activating tyrosine phosphatase activity to inhibit cell proliferation and the metastasis-associated properties of A431 cancer cells. Our work suggests that [D-Trp(6)]LHRH may be therapeutically useful in limiting the tumor growth and metastasis of some neoplasms.

Antineoplastic Agents, Hormonal↗