Lutenizing Hormone-releasing Hormone Research Articles

MP45-20 VARIABILITY IN TESTOSTERONE MEASUREMENT BETWEEN RADIOIMMUNOASSAY (RIA), CHEMILUMINESCENCE ASSAY(CLIA) AND LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY(MS) AMONG PROSTATE CANCER PATIENTS ON ANDROGEN DEPRIVATION THERAPY (ADT)

You have accessJournal of UrologyCME1 May 2022MP45-20 VARIABILITY IN TESTOSTERONE MEASUREMENT BETWEEN RADIOIMMUNOASSAY (RIA), CHEMILUMINESCENCE ASSAY(CLIA) AND LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY(MS) AMONG PROSTATE CANCER PATIENTS ON ANDROGEN DEPRIVATION THERAPY (ADT) Raj Tiwari, Katherine Lajkosz, Mohamed Baker Berjaoui, Yazan Qaoud, Clive Woffendin, Patrick Caron, Chantal Guillemette, and Neil Fleshner Raj TiwariRaj Tiwari More articles by this author , Katherine LajkoszKatherine Lajkosz More articles by this author , Mohamed Baker BerjaouiMohamed Baker Berjaoui More articles by this author , Yazan QaoudYazan Qaoud More articles by this author , Clive WoffendinClive Woffendin More articles by this author , Patrick CaronPatrick Caron More articles by this author , Chantal GuillemetteChantal Guillemette More articles by this author , and Neil FleshnerNeil Fleshner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002611.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Monitoring testosterone (T) levels is increasingly being recommended to guide the effectiveness of ADT in the treatment of advanced prostate cancer (PCa). T levels of less than 20 ng/dl (0.7 nmol/L) on therapy have been associated with better outcomes with some clinicians advocating medication switch for patients who do not achieve this level. Three main assays for T measurement exist including RIA, CLIA and MS. CLIA and RIA are commonly used worldwide, however MS is regarded as the reference standard. We set out to determine the discordance rates of T measurements amongst men on ADT. METHODS: A retrospective McCain GU biobank (MGB) database review of PCa men on lutenizing hormone-releasing hormone (LHRH) monotherapy for 3 or more months was conducted. Patients with exposure to second line hormone agents or chemotherapy were excluded. Corresponding serum samples were identified and split in triplicate for measurement via all three assays. Observational data was reported and T measurements were compared analyzing for variability looking for categorical concordance. Over and under-estimation rates were calculated. RESULTS: 95 patients were included with a mean age of 70 (50-92) years. 80 (88%) patients were on LHRH agonist therapy. Mean ADT duration was 24.1 (3-144) months. Mean T levels were significantly different at p<0.001 with MS at 11.4 (0.1-282) ng/dL, CLIA at 23.4 (20-204) ng/dL and RIA at 15.1 (0.1-170.5) ng/dL. 95% of patients had T ≤20ng/dL by MS and CLIA as compared to only 80% by RIA. After subdividing into T categories of ≤20, 20-50 and ≥50ng/dL concordance analysis showed that 4.3% and 18.9% of ST measured by MS would have a different category result when remeasured by CLIA (Kappa 0.84) or RIA (Kappa 0.50) respectively. 16.8% of T measured by CLIA would also have a different category result when remeasured by RIA (Kappa 0.58). Intra-class correlation coefficient between all 3 measures was 0.83 (95% CI 0.77-0.88). CLIA and RIA overestimated T in 66% of patients with T<20 ng/dL measured by MS. Conversely CLIA and RIA underestimated T in only 2.4% with T>20ng/dL measured by MS. CONCLUSIONS: There is significant variability in T measured with RIA, CLIA and MS. CLIA and RIA overestimated T levels in majority of patients leaving a concern of misdiagnosing true castrate patients instead as being inadequately treated. Clinicians should be mindful of variability in T measurements by assays when using them for decision making among PCa patients on ADT. Source of Funding: Internal funding from University Health Network © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e771 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Raj Tiwari More articles by this author Katherine Lajkosz More articles by this author Mohamed Baker Berjaoui More articles by this author Yazan Qaoud More articles by this author Clive Woffendin More articles by this author Patrick Caron More articles by this author Chantal Guillemette More articles by this author Neil Fleshner More articles by this author Expand All Advertisement PDF DownloadLoading ...

Prostate‐specific antigen response after short‐term hormone therapy plus external‐beam radiotherapy and outcome in patients treated on Radiation Therapy Oncology Group study 9413

The objective of this study was to assess the impact of a prostate-specific antigen (PSA) complete response (PSA-CR), measured at the end of external-beam radiotherapy and short-term hormone therapy, on treatment outcomes. The phase 3 Radiation Therapy Oncology Group 9413 trial, as part of its original protocol, used the assessment of PSA-CR (ie, PSA ≤0.3 ng/mL) at the end of short-term HT as a secondary endpoint. Short-term HT consisted of futamide plus a lutenizing hormone-releasing hormone agonist for 4 months. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. Cumulative incidence was used to estimate biochemical failure, distant metastasis, and disease-specific survival. Univariate and multivariate analyses were performed to correlate PSA-CR after short-term hormone therapy with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone status. Phoenix consensus definition was used to define PSA failure. For 1070 evaluable patients, the median PSA at the end of short-term hormone therapy was 0.2 ng/mL. In total, 744 patients (70%) had a PSA-CR. At a median follow-up of 7.2 years, failure to obtain a PSA-CR was associated significantly with worse disease-specific survival (P = .0003; hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.38-2.97), with worse disease-free survival (P = .003; HR, 1.28; 95% CI, 1.09-1.50), and with a higher incidence of distant metastasis (P = .0002; HR, 1.92; 95% CI, 1.37-2.69) and biochemical failure (P < .0001; HR, 1.57; 95% CI, 1.29-1.91). Other factors that were associated with worse disease-specific survival were Gleason scores from 8 to 10 (P = .0002; HR, 3.06; 95% CI, 1.71-5.47) and PSA levels >20 ng/mL (P = .04; HR, 1.55; 95% CI, 1.02-2.30). The current results indicated that failure to obtain a PSA-CR (PSA ≤0.3 ng/mL) after short-term hormone therapy and external-beam radiotherapy appears to be an independent predictor of unfavorable outcomes and could help identify patients who may benefit from the addition of long-term androgen ablation.

A review of the control of reproduction and hormonal manipulations in finfish species

Control of reproductive is essential for the sustainability of commercial aquaculture production. The reasons for breakage of ovulation and spawning is failure of the pituitary to release gonadotropin hormones. Gonadotropin hormones secretion is under a dual control, by gonadotropin releasing hormone (GnRH), and inhibition by dopamine on the actions of GnRH. The inhibitory actions of dopamine on GTH secretion can vary in potency between species. In some fish it is necessary to use dopamine blocker, such as domperidone, results in potentiation of the actions of GnRH analoge, leading to a large release of GTH-II and ovulation. In some other injection of a high dose of GnRH analoge alone is effective. In several marine species GTH-II secretion is not under dopaminergic inhibitory control but sensitive to exogenous analoge hormones (GnRHa). In many fishes, synthetic analoges of lutenizing hormone-releasing hormone (LHRHa) are widely used for inducing spawning. In several tropical freshwater and marine finfishes the human chorionic gonadotropin (HCG), pituitary homogenate and semi-purified fish gonadotropin are used. Rrecently the replacement of natural GnRH are used and had resulted in a centuple increase in the effectiveness of luteinizing hormones secretion induction. Key word: Reproduction induced spawning, dopamine antagonists, GTH-II- HCG

Effect of Inhaled Corticosteroids on Growth and Puberty in Egyptian Asthmatic Children and Adolescents

Growth suppression and delayed puberty may be major concerns for Inhaled Corticosteroids (ICS) treatment in children. Thus, we aimed to assess the effect of long-term ICS on growth and pubertal status in 30 asthmatic children and adolescents in comparison to 20-matched healthy subjects. Auxological measurements, Tanner staging and bone age assessment were performed. Measurements of basal and Lutenizing hormone releasing hormone (LHRH) stimulated follicle stimulating hormone (FSH) and Lutenizing hormone (LH) were done for patients only. In addition, pelvic ultrasound for measurements of uterine length and right ovarian volume was done for females aged > 11 years. Patients' height, bone age and their Standard Deviation Scores (SDSs) were significantly lower, while weight SDSs were significantly higher than controls. ICS at doses > 400 microg/day negatively affected height and its SDS (OR: 8.5, 95% CI: 2.15-33.8), whereas the use of ICS for > 1 year significantly affected all auxological parameters with a particular risk on height SDS (OR: 9, 95% CI = 3.10-10.64) and weight for height SDS (OR: 6.82, 95% CI: 1.36-34.27). Significantly lower stimulated gonadotropins were encountered at doses > 400 microg/day, while a duration > 1 year was associated with significantly lower basal and stimulated gonadotropins. Logistic analysis revealed that the use of ICS for > 1 year carried the highest risk of association with low stimulated FSH (OR: 5.80, 95%, CI: 1.54-33.70) and LH (OR: 8.31, 95% CI: 1.83-50.47). In conclusion, ICS at doses > 400 microg/day carry a significant risk of retarding height of asthmatic children while their continuous use for > 1 year carries significant risks of short stature, weight gain and delayed puberty.

Reply to Genetic polymorphisms of CYP2D6*10 and CYP2C19*2,*3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen

We are grateful to Dr. Goetz et al for their queries, which we consider both important and useful for a better understanding of our study. Our responses to these questions are set out below. Unfortunately, the exact percentage of patients who refused to give their consent for the blood collection during the study period is unknown; however, the estimated refusal rate was very low (a few percentage points). Blood collection was performed before surgery from all patients who had provided consent. Patients who had estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancers received adjuvant tamoxifen, so that all ER-negative tumors were PR-positive tumors. We included patients who had received adjuvant tamoxifen and chemotherapy and/or lutenizing hormone-releasing hormone agonist, because it has been proven that tamoxifen significantly improves recurrence-free survival rates even in conjunction with these concomitant treatments. Postoperative surveillance consisted of a physical examination every 3 to 6 months for 2 years, every 6 months for 2 to 5 years, and once a year thereafter and was combined with a blood test and chest x-ray (mammography every year). Nine patients were lost to follow-up, 20 patients developed recurrences, and none of the patients without recurrence died. Our study was underpowered, as pointed out by Goetz et al. Therefore, for our study,1 we conducted an exploratory meta-analysis of the studies reported to date.2, 3 That analysis indicated that there was no statistically significant impact of the cytochrome p450 (CYP) genotype CYP2D6*10/*10 on prognosis. The salient point of our report is that we studied the impact of this polymorphism on the effects of tamoxifen on its target organs, such as uterus, bone, and liver, on the assumption that this polymorphism, if it really does influence the effect of tamoxifen, affects these organs more markedly than tumors, because it is believed that the response to tamoxifen essentially is homogeneous for normal tissues (target organs) but heterogeneous for tumors. We were able to demonstrate that the CYP2D6*10/*10 genotype essentially has no impact on the effects of tamoxifen on these target organs, suggesting that changes in tamoxifen metabolite levels detected in the CYP2D6*10/*10 genotype are not clinically important enough to influence the effects of tamoxifen on these organs. Thus, it has been speculated that the CYP2D6*10/*10 genotype also has no significant impact on the effects of tamoxifen on prognosis. However, as clearly pointed out by Goetz et al, future studies that include a larger number of patients are needed to reach a definitive conclusion regarding the impact of the CYP2D6*10/*10 genotype on prognosis. Shinzaburo Noguchi MD*, Masatsugu Okishiro MD*, * Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Immunologic Mechanisms Mediate Benefits of Lutenizing Hormone-Releasing Hormone (LH-RH) in High Risk Premenopausal Breast Cancer Patients (HR-Pre-BC).

Abstract Background: Systematic reviews have found that LH-RH agonists are effective in the treatment of premenopausal women with early breast cancer. In an extended phase II study, 180 premenopausal women with HR-Pre-BC were treated with an LH-RH analogue in order to protect ovaries from the damage of chemotherapy. We hypothesized that the benefits of LH-RH administration could extend, far beyond ovarian protection, to the improvement of immune function and to the decrease of vascular endothelial growth factor (VEGF). In fact estradiol (E2) at physiological doses not only expands T regulatory cells (T-regs) in different tissues but also increases expression of the Foxp3 gene, a hallmark for CD4+CD25+ T-reg cell function, and the interleukin-10 gene as well. In addition, recent studies indicate that E2 modulates VEGF expression in breast cancer cells through transcriptional activation.Methods: From 05-1997 to 05-2007 180 patients with HR-Pre-BC were entered into the study. At baseline, one week before chemotherapy, patients received an LH-RH analogue which was continued for five years. Adjuvant chemotherapy was tailored to the peculiar biologic features of each patient, including cyclophosphamide, methotrexate, and 5-fluorouracil in 24 patients, an anthracycline and taxane based regimens in 156 patients (40 with positive c-erb-2 tumors). Seventeen patients with &amp;gt; 10 positive axillary lymph nodes and 36 patients with triple negative tumors, received a platinum-based consolidation high-dose chemotherapy with or without autologous peripheral blood progenitor cell transplantation, respectively. Radiation therapy was administered to 145 patients. During the 5 years of LH-RH analogue, patients received a strong psychological support, biphosphonates, and after the end of chemotherapy, estrogen receptor positive (ER+) patients received an aromatase inhibitor.Results: Characteristics of patients. The mean patient age was 42 years (range, 26–50 yrs). One hundred-twenty five women were ER+, 55 were estrogen receptor negative (ER-). Total number of positive nodes was 479, with a mean of 2.6 for each patient (range 0-25). UICC stage was II in 114 women and III in 66 women. All patients had their serum E2 suppressed to values &amp;lt; 40 pg/mL. A statistically significant improvement was observed in lymphocyte number (p&amp;lt; 0.005), and a decrease in T-reg number (p&amp;lt; 0.005) and VEGF (p&amp;lt; 0.005) with respect to baseline values, after LH-RH administration. After a median follow-up of 97 months, 10-years overall progression-free survival and overall survival rate were both 83.2% with no statistical significant difference between ER+ and ER- patients.Conclusions: These data show that the administration of an LH-RH analogue improves lymphocyte number, decreases T-regs and VEGF, and seems to improve the expected outcome of HR-Pre-BC patients through immunologic mediated mechanisms. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4092.

Twenty years of controversy surrounding combined androgen blockade for advanced prostate cancer

The current issue of Cancer includes a report on a concise, randomized controlled trial (RCT) with long‐term follow‐up that favors combined androgen blockade with bicalutamide versus lutenizing hormone‐releasing hormone monotherapy in Japanese men with locally advanced and metastatic prostate cancer. It has been 20 years since the first RCT on CAB was published, and the debate continues.

Type 2 Diabetes Mellitus Accompanied by Isolated Adrenocorticotropic Hormone Deficiency and Gastric Cancer

A 69-year-old man with type 2 diabetes mellitus was admitted to our hospital because of appetite loss, nausea and vomiting. Gastroscopy revealed gastric cancer. Levels of plasma cortisol were decreased. Neither adrenocorticotropic hormone (ACTH) nor cortisol levels were adequately increased in response to a mixed intravenous administration of corticotropin-releasing hormone, growth hormone-releasing hormone, thyrotropin-releasing hormone and lutenizing hormone-releasing hormone, although other pituitary hormones were increased adequately. He was diagnosed as having isolated ACTH deficiency (IAD). Anti-pituitary antibody and anti-parietal cell antibody were positive. At least in part, these antibodies may play pathogenic roles of development of IAD and gastric cancer.

Amphoterin induction in prostatic stromal cells by androgen deprivation is associated with metastatic prostate cancer

Amphoterin, the major product of the high mobility group-1 gene, is a ligand associated with cancer invasion and metastasis through activation of the receptor for advanced glycation end products (RAGE). Expression of amphoterin and RAGE was examined in prostatectomy specimens from 40 patients with pT3 prostate cancer (18 non-metastatic and 22 metastatic) preoperatively treated with lutenizing hormone-releasing hormone (LH-RH) agonist. Amphoterin expression was detected in tumor cells of 6 (27%) metastatic and 0 non-metastatic cases (p<0.0001). Amphoterin was also detected in prostatic stromal cells of 14 (63%) metastatic cases and 2 (11%) non-metastatic cases (p=0.0010). RAGE production was detected in cancer cells of 16 (73%) metastatic and 6 (33%) non-metastatic cases (p=0.0244). A total of 2 (22%) non-metastatic and 16 (73%) metastatic cases showed co-expression of amphoterin and RAGE in tumor cells or in tumor cells and stromal cells (p=0.0001). The in vitro invasive capacity of PC-3, a prostatic cancer cell line that co-expressed amphoterin and RAGE, was suppressed by treatment with amphoterin antisense S-oligodeoxynucleotide (ODN). Primary cultured human prostatic stromal cells secreted no amphoterin; however, amphoterin secretion was induced by androgen deprivation. The conditioned medium of human prostatic stromal cells deprived of androgen recovered the in vitro invasive capacity of PC-3 cells suppressed by amphoterin antisense S-ODN. These results suggest that androgen deprivation provides a paracrine interaction between cancer and stromal cells through the RAGE-amphoterin system in advanced prostate cancer.

Delta opioid receptors are involved in morphine-induced inhibition of luteinizing hormone releasing hormone in SK-N-SH cells

Opioids play an important role in the regulation of lutenizing hormone releasing hormone (LHRH). In the present study, we attempted to find out the subtype of opioid receptors involved in the inhibitory effect of morphine on LHRH. Experiments were conducted on SK-N-SH neuroblastoma cells that express both μ and δ opioid receptors, LHRH mRNA, and release the LHRH peptide. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of LHRH. LHRH level was decreased by 1000 μM of morphine regardless of the duration of exposure or differentiation status of the SK-N-SH cells and was not reversed by naloxone. Selective antagonism of μ opioid receptors, but not δ opioid receptors, allowed lower concentrations (1–100 μM) of morphine to inhibit LHRH. The results of this study imply that (1) δ opioid receptors may mediate the inhibitory effect of lower concentrations of morphine on LHRH levels in SK-N-SH cells, and (2) inhibition of LHRH level by high concentrations of morphine may involve systems other than opioid receptors.

Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease that affects males. It is caused by the expansion of a polyglutamine (polyQ) tract in androgen receptors. Female carriers are usually asymptomatic. No specific treatment has been established. Our transgenic mouse model carrying a full-length human androgen receptor with expanded polyQ has considerable gender-related motor impairment. This phenotype was abrogated by castration, which prevented nuclear translocation of mutant androgen receptors. We examined the effect of androgen-blockade drugs on our mouse model. Leuprorelin, a lutenizing hormone-releasing hormone (LHRH) agonist that reduces testosterone release from the testis, rescued motor dysfunction and nuclear accumulation of mutant androgen receptors in male transgenic mice. Moreover, leuprorelin treatment reversed the behavioral and histopathological phenotypes that were once caused by transient increases in serum testosterone. Flutamide, an androgen antagonist promoting nuclear translocation of androgen receptors, yielded no therapeutic effect. Leuprorelin thus seems to be a promising candidate for the treatment of SBMA.

Combined effects of lutenizing hormone-releasing hormone analogue with antiestrogen on rat mammary tumors

The efficacy of luteining hormone-releasing hormone (LH-RH) analogue, buserelin, combind with tamoxifen (TAM) on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors was investigated. Low-dose of TAM (L-TAM), 1 mg/kg daily, significantly suppressed the growth of tumors compared with no treatment group. High-dose of TAM (H-TAM), 10 mg/kg daily, suppressed growth considerably, and there was a significant difference in the antitumor effect between the L-TAM group and the H-TAM group. The combined treatment using buserelin and L-TAM significantly suppressed the tumor growth compared with the treatment using each single agent. LH-RH analogue actually reduced serum estradiol (E2) levels and enhanced the antitumor effect brought by a therapeutical dose of TAM. The reduction of serum cholesterol levels as a beneficial effect of TAM was reserved when combined with buserelin. Insulin-like growth factor 1 (IGF-1) expressions in tumors were significantly decreased in the buserelin and L-TAM group. These results support the usefulness of this combination in clinical use.

Hypothalamic lutenizing hormone-releasing hormone (LHRH) neurons: Insights into oscillatory peptide secretion

Hypothalamic lutenizing hormone-releasing hormone (LHRH) neurons: Insights into oscillatory peptide secretion

Maximum androgen-blockade with medical or surgical castration in advanced prostate cancer: A meta-analysis of nine published randomized controlled trials and 4128 patients using flutamide.

With the recent Southwest Oncology Group (SWOG) publication of their metastatic prostate cancer clinical trial results, which concluded that orchiectomy and flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does not significantly improve survival (NCI 0105), and the 1989 publication from the same cooperative group indicating a 24% improvement in survival for MAB therapy with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may well be undecided about the likelihood of clinical benefits with flutamide in combination with medical or surgical castration. To better characterize this important therapeutic decision, we assessed the survival benefit of MAB therapy with flutamide through a meta-analysis of up-to-date information from studies reported/conducted from 1989 through 1998. All peer-reviewed published randomized controlled trials comparing treatment with flutamide plus either lutenizing hormone releasing hormone (LhRH) agonists or orchiectomy as MAB treatment with LhRH or orchiectomy alone were included. The primary objective of the study was to form a combined estimate and confidence interval for the hazard ratio (as measured by the relative risk (RR) of survival in a comparison of castration vs MAB) summarizing the effect of flutamide treatment on overall survival. Directly extracted estimates of the log hazard ratio were used if available (1 study); if not, either an estimate of the RR based on a reported P-value from a log rank test (7 studies) or a discrete proportional hazards approximation based on reconstructed annual life tables for the treatment arms (1 study) were used. Nine studies with 4128 patients with advanced prostate cancer were included in these analyses. Pooled estimates demonstrated a 10% improvement in overall survival with flutamide as MAB therapy (relative risk (RR)=0.90, 95% Confidence Interval=0.79, 1.00). The currently available updated evidence from randomized trials shows a 10% benefit in overall survival with flutamide as MAB therapy in comparison to conventional castration, almost identical to the estimate reported in the recently published Southwest Oncology Group Study (NCI 0105).

The nitric oxide hypothesis of brain aging.

Nitric oxide synthase (NOS)-containing neurons are found in many loci throughout the central nervous system, which include the cerebral cortex, the cerebellum, the hippocampus, and the hypothalamus. NO plays a very important role in control of neuronal activity in all of these areas by diffusing into neurons where it activates soluble guanylate cyclase (sGC) leading to generation of cyclic guanosine monophosphate (cGMP) and cyclooxygenase 1 leading to generation of prostaglandins. Both of these active agents are involved in mediating the actions of NO, the first gaseous transmitter. In the cerebellum, NO is extremely important and it is also thought to mediate long-term potentiation in the hippocampus. Various stresses and corticoids have been shown in monkeys and also in rodents to cause neuronal cell death. This may be via the stimulation of glutamic acid release, which by N-methyl-D-aspartate (NMDA) receptors causes release of NO, which can lead to neuronal cell death. In the hypothalamus,. NO stimulates corticotropin-releasing hormone (CRH), prolactin releasing factor, growth hormone-releasing hormone (GHRH), and somatostatin, lutenizing hormone-releasing hormone (LHRH), but not follicle stimulating hormone-releasing factor (FSHRF) release. In situations of increased release of NO in the hypothalamus, it could cause neuronal cell death. Following bacterial or viral infections, toxic products of the ineffective agents, such as bacterial lipopolysaccharide (LPS), circulate to the brain, where they induce interleukin-1 and iNOS mRNA and synthesis. After several hours delay, massive quantities of NO are released. Induction of iNOS occurs in the choroid plexus, meninges, in circumventricular organs, and in large numbers of iNOS neurons in the arcuate and paraventricular nuclei. The large amounts of NO released by iNOS may well produce death not only of neurons but also glial. Repeated bouts of systemic infection even without direct neural involvement could result in induction of iNOS in the central nervous system and lead to large fall out of neurons in hippocampus to impair memory, hypothalamus to decrease fever, and neuroendocrine response to infection, and could play a role in the pathogenesis of degenerative neuronal diseases of aging, such as Alzheimers. The largest induction of iNOS occurs in the anterior pituitary and pineal glands. The damage to the pituitary could also impair responses to stress and infection, and the release of NO during infection could be responsible for the degenerative changes in the pineal and diminished release of melatonin, an antioxident, and consequently, an antiaging hormone, that occur with age.

Bicuculline infusion advances the timing of Fos expression in LHRH neurons in the preoptic area of proestrous rats.

The effect of bicuculline (BIC) on Fos expression in lutenizing hormone-releasing hormone (LHRH) neurons was examined by immunocytochemistry. Proestrous rats were infused with saline (SAL 1400, n = 4) or BIC (BIC 1400, n = 5) for 3 h (10.00-13.00 h) and were killed at 1400 h. Three control rats (SAL 1700), which received saline infusion, were killed at 1700 h. In both the BIC 1400 group and the SAL 1700 group, many LHRH neurons in the preoptic area expressed Fos, but those in the SAL 1400 group did not. The distribution and proportion of LHRH neurons expressing Fos in the BIC 1400 group were identical to those in the SAL 1700 group. We conclude that GABAergic neurons play a critical role in inducing LH surge by controlling LHRH neuronal activity.

Morphological Interactions between Glial Fibrillary Acidic Protein (GFAP)-like Immunoreactive Elements and Lutenizing Hormone Releasing Hormone (LHRH)-like Immunoreactive Nerve Endings in the Median Eminence of the Rat. Double Labeling Immunoelectron Microscopic Study.

In the present study, interactions between lutenizing hormone releasing hormone (LHRH) -like immunoreactive (LHRH-LI) nerve endings and processes of tanycytes and/or astrocytes in the median eminence (ME) particularly its external layer were investigated by double labeling immunoelectron microscopy employing antibodies against glial fibrillary acidic protein (GFAP) and LHRH. GFAP-like immunoreactivity was observed in some tanycytes throughout the ME and/or astrocytes in the subependymal layer of the ME. In the palisade layer of the ME, GFAP-like immunoreactive (GFAP-LI) elements were frequently seen to make intimate contact with LHRH-LI nerve endings. LHRH-LI nerve endings and processes of the tanycytes and/or astrocytes were also found to direct contact with the basement membrane of the pericapillary space. And they were partially engulfed each other in the vicinity of the perivascular region. The above findings strongly suggest that the processes of tanycytes and/or astrocytes with intimate communication of cerebrospinal fluid in the third ventricle may play a role in regulation of secretion of LHRH into the portal vessels.

606 Interaction between glial fibrillary acidic protein (GFAP)-like immunoreactive tanycytes and tyrosine hydroxylase (TH), lutenizing hormone releasing hormone (LHRH)-like immunoreactive nerve endings in the median eminence of the rat.-double labeling immunoelectron microscopic study

606 Interaction between glial fibrillary acidic protein (GFAP)-like immunoreactive tanycytes and tyrosine hydroxylase (TH), lutenizing hormone releasing hormone (LHRH)-like immunoreactive nerve endings in the median eminence of the rat.-double labeling immunoelectron microscopic study

Klinefelter Syndrome, Rare Variant 49, XXXXY

Klinefelter Syndrome, Rare Variant 49, XXXXY

Effects of serum testosterone level with buserelin on the activities of drug and testosterone hydroxylase and on the content of a male-specific form of cytochrome P-450 in male rats

The effects of administration of buserelin, a synthetic agonist of lutenizing hormone-releasing hormone (LH-RH), on the content of P-450-male, a male specific form of cytochrome P-450, and the activities of drug and testosterone hydroxylases were examined in liver microsomes of male rats. Administration of buserelin resulted in a decrease in the serum level of testosterone in a dose-dependent manner. Similar decreases were seen in the activities of aminopyrine N-demethylase, 7-propoxycoumarin O-depropylase and testosterone 2α- and 16α-hydroxylases, but not in the activity of aniline p-hydroxylase. Thus, correlations were observed between the serum level of testosterone and the activities of drug and testosterone hydroxylases except for aniline p-hydroxylase. These results indicate that the drug and testosterone hydroxylases are affected sensitively and sequentially by the changes in the testosterone levels in the body.