Contribution of growth hormone-releasing hormone and somatostatin to decreased growth hormone secretion in elderly men

Objective. The pathophysiology of the decline in circulating growth hormone (GH) concentrations that may occur with ageing remains elusive. We have investigated the potential contributions of decreased endogenous GH-releasing hormone (GHRH) and increased somatostatin secretion to this phenomenon.Design and methods. The strategy used was to stimulate GH secretion in 8 young (20 - 24 years old, body mass index (BMI) 22.8 ± 2.8 kg/m2) and 8 elderly (68- 82 years old, BMI 23.4 ± 1.6 kg/m2) male subjects on separate occasions by means of: (i) intravenous bolus 0.5 ).lg/kg D-Ala2 GHRH(1-29)-NH alone; (ii) 0.5 μg/kg GHRH after pretreatment with two oral doses of 50 mg atenolol (to inhibit somatostatin secretion); (iii) 1.25 mg oral bromocriptine alone (to increase endogenous GHRH and/or inhibit somatostatin); (iv) 50 mg oral atenolol plus 1.25 mg oral bromocriptine; and (v) 0.5 μg/kg GHRH after pre-treatment with 1.25 mg oral bromocriptine.Results. The elderly men had a significantly lower peak and area under curve (AUC) GH response to intravenous GHRH when compared with 8 young men (peak 3.1 ± 1.0 ng/ml v. 21.6 ± 5.0 ng/ ml, AUC 205 ±56 ng/ ml/min v.1 315 ± 295 ng/ ml/ min, P < 0.05). Pre-treatment with atenolol before GHRH administration produced no significant increase in peak and AUC GH response in both groups, whlch remained lower in the elderly men than in their young counterparts (peak 5.5 ±1.8 ng/ ml v. 29.3 ± 7.0 ng/ml, AUC 327 ± 90 ng/ml/min v. 2 017 ± 590 ng/ ml/min, P < 0.05). Bromocriptine alone did not cause a significant rise in GH concentration in either elderly or young subjects (peak 3.1 ± 1.1 v. 8.8 ± 3.2 ng/ ml, P > 0.05). When atenolol was administered before bromocriptine, both groups responded but the elderly subjects had a significantly greater peak and AUC response (peak 3.6 ± 0.7 v. 10:7 ± 2.1 ng/ ml; AUC 191 ± 39 v. 533 ± 125 ng/ ml/ min, P < 0.05). Bromocriptine given before GHRH failed to potentiate GHRH action on GH release in either group. Of 5 elderly men who tmderwent further evaluation of GH secretory ability, 2 subjects had GH levels > 10 ng/ rnl, either basally or after intravenous GHRH. The remaining 3 had an initially impaired GH response to bolus intravenous GHRH. After 100 μg GHRH subcutaneously twice daily for up to 2 weeks the GH responses to intravenous bolus GHRH (0.5μg /kg) were reassessed. One exhibited a normal response (> 10 ng/ rnl) after 1 week of daily GHRH treatment, another had a nearnormal response after 2 weeks (9.7 ng/ rnl), while the third still had an impaired response by the end of the 2-week treatment period (3.2 ng/ ml).Conclusions. The restoration of endogenous GH secretion in these elderly subjects by means of GHRH priming, and the failure of manipulation of somatostatinergic tone to restore a normal GH response to GHRH suggests that somatotroph atrophy due to a reduction in endogenous GHRH secretion is the principal cause of the diminished GH secretion with ageing

University of California 4-H Latino Initiative: Experiences of Bicultural and Bilingual Staff

We report data from the first year of an initiative to engage Latino youth and families in the 4-H Youth Development Program, managed by the University of California. Through qualitative questionnaires and focus group interviews, we analyzed experiences of 6 new bilingual and bicultural program staff, hired specifically to implement youth development programming to reach Latino youth. Staff reported a steep learning curve, with competing demands to build relationships, engage youth, and show results. Lessons learned may help shape activities that other youth development programs may consider in similar efforts

First direct observation of Dirac fermions in graphite

Originating from relativistic quantum field theory, Dirac fermions have been recently applied to study various peculiar phenomena in condensed matter physics, including the novel quantum Hall effect in graphene, magnetic field driven metal-insulator-like transition in graphite, superfluid in 3He, and the exotic pseudogap phase of high temperature superconductors. Although Dirac fermions are proposed to play a key role in these systems, so far direct experimental evidence of Dirac fermions has been limited. Here we report the first direct observation of massless Dirac fermions with linear dispersion near the Brillouin zone (BZ) corner H in graphite, coexisting with quasiparticles with parabolic dispersion near another BZ corner K. In addition, we report a large electron pocket which we attribute to defect-induced localized states. Thus, graphite presents a novel system where massless Dirac fermions, quasiparticles with finite effective mass, and defect states all contribute to the low energy electronic dynamics.Comment: Nature Physics, in pres

Contribution of growth hormone-releasing hormone and somatostatin to decreased growth hormone secretion in elderly men

Objective. The pathophysiology of the decline in circulating growth hormone (GH) concentrations that may occur with ageing remains elusive. We have investigated the potential contributions of decreased endogenous GH-releasing hormone (GHRH) and increased somatostatin secretion to this phenomenon.Design and methods. The strategy used was to stimulate GH secretion in 8 young (20 - 24 years old, body mass index (BMI) 22.8 ± 2.8 kg/m2 ) and 8 elderly (68 - 82 years old, BMI 23.4 ± 1.6 kg/m2 ) male subjects on separate occasions by means of: (i) intravenous bolus 0.5 pg/kg D-Ala2 GHRH(1-29)-NR alone; (ii) 0.5 pg/kg GHRH after pretreatment with two oral doses of 50 mg atenolol (to inhibit somatostatin secretion); (iii) 1.25 mg oral bromocriptine alone (to increase endogenous GHRH and/or inhibit somatostatin); (iv) 50 mg oral atenolol plus 1.25 mg oral bromocriptine; and (v) 0.5 Jlg/kg GHRH after pre-treatment with 1.25 mg oral bromocriptine.Results. The elderly men had a significantly lower peak and area under curve (ADC) GH response to intravenous GHRH when compared with 8 yoU?g men (peak 3.1 ± 1.0 ng/ml v. 21.6 ± 5.0 ng/ml, ADC 205 ± 56 ng/ml/min v. 1 315 ± 295 ng/ml/min, P < 0.05). Pre-treatment with atenolol before GHRH administration produced no significant increase in peak and AUC GH response in both groups, which remained lower in the elderly men than in their young counterparts (peak 5.5 ±·1.8 ng/ml v. 29.3 ± 7.0 ng/ml, ADC 327 ± 90 ng/ml/min v. 2 017 ± 590 ng/ml/min, P < 0.05). Bromocriptine alone did not cause a significant rise in CH concentration in either elderly or young subjects (peak 3.1 ± 1.1 v. 8.8 ± 3.2 ng/ml, P > 0.05). When atenolol was administered before bromocriptine, both groups responded but the elderly subjects had a significantly greater peak and ADC response (peak 3.6 ± 0.7 v. 10:7 ± 2.1 ng/ml; ADC 191 ± 39 v. 533 ± 125 ng/mllmin, P < 0.05). Bromocriptine given before CHRH failed to potentiate CHRH action on CH release in either group. Of 5 elderly men who underwent further evaluation of CH secretory ability, 2 subjects had CH levels> 10 ng/ml, either basally or after intravenous CHRH. The remaining 3 had an initially impaired CH response to bolus intravenous GHRH. After" 100 pg CHRH subcutaneously twice daily for up to 2 weeks the GH responses to intravenous bolus CHRH (0.5 flg/kg) were reassessed. One exhibited a normal response (> 10 ng/ml) after 1 week of daily CHRH treatment, another had a nearnormal response after 2 weeks (9.7 ng/ml), while the third still had an impaired response by the end of the 2-week treatment period (3.2 ng/ml).Conclusions. The restoration of endogenous CH secretion in thes~ elderly subjects by means of GHRH priming, and the failure of manipulation of somatostatinergic tone to restore a normal CH response to CHRH suggests that somatotroph atrophy due to a reduction in endogenous CHRH secretion is the principal cause of the diminished CH secretion with ageing

Meeting report from the Prostate Cancer Foundation PSMA theranostics state of the science meeting

IntroductionThe Prostate Cancer Foundation (PCF) convened a PCF prostate-specific membrane antigen (PSMA) Theranostics State of the Science Meeting on 18 November 2019, at Weill Cornell Medicine, New York, NY.MethodsThe meeting was attended by 22 basic, translational, and clinical researchers from around the globe, with expertise in PSMA biology, development and use of PSMA theranostics agents, and clinical trials. The goal of this meeting was to discuss the current state of knowledge, the most important biological and clinical questions, and critical next steps for the clinical development of PSMA positron emission tomography (PET) imaging agents and PSMA-targeted radionuclide agents for patients with prostate cancer.ResultsSeveral major topic areas were discussed including the biology of PSMA, the role of PSMA-targeted PET imaging in prostate cancer, the physics and performance of different PSMA-targeted PET imaging agents, the current state of clinical development of PSMA-targeted radionuclide therapy (RNT) agents, the role of dosimetry in PSMA RNT treatment planning, barriers and challenges in PSMA RNT clinical development, optimization of patient selection for PSMA RNT trials, and promising combination treatment approaches with PSMA RNT.DiscussionThis article summarizes the presentations from the meeting for the purpose of globally disseminating this knowledge to advance the use of PSMA-targeted theranostic agents for imaging and treatment of patients with prostate cancer