Effects of estrogen and growth hormone on skeleton in the ovariectomized rat with hypophysectomy

1997 ◽  
Vol 273 (4) ◽  
pp. E734-E742 ◽  
Author(s):  
James K. Yeh ◽  
Meng-Meng Chen ◽  
John F. Aloia
Keyword(s):  
Growth Hormone ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Combined Treatment ◽  
Serum Levels ◽  
Hormone Deficiency ◽  
High Dose ◽  
Sprague Dawley ◽  
High Doses

To investigate whether growth hormone (GH) and 17β-estradiol (E2) replacement can prevent osteopenia induced by pituitary and ovarian hormone deficiency [by hypophysectomy and ovariectomy (HX+OV)], we administered relatively low doses of GH (2.3 IU ⋅ kg−1 ⋅ day−1) and E2 (100 μg ⋅ kg−1 ⋅ wk−1) in experiment 1 and relatively high doses of GH (13.5 IU ⋅ kg−1 ⋅ day−1) and E2 (3,500 μg ⋅ kg−1 ⋅ wk−1) in experiment 2 to 2-mo-old HX+OV Sprague-Dawley rats for 6 wk. Our data show that the HX+OV of rats results in diminished periosteal bone formation, longitudinal bone growth, and decreased cancellous bone volume. Administration of either the low or high dose of GH to these rats increased their systemic growth, serum levels of osteocalcin, and cortical bone formation. Either low or high doses of GH or E2 alone only partially prevent cancellous bone loss. However, the combined treatment of GH plus E2 resulted in an additive increase in the cancellous bone mass. We conclude that the additive effect of GH plus E2 on cancellous bone is attributed to the suppressive effect of E2 on bone resorption and the anabolic effect of GH on bone formation.

BIOASSAY OF GROWTH HORMONE

1974 ◽  
Vol 75 (4) ◽  
pp. 669-682 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Bone Growth ◽  
Control Period ◽  
Growth Stimulation ◽  
Sprague Dawley ◽  
Hormone Administration ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
Operative Control ◽  
Sensitivity Specificity

ABSTRACT The growth stimulating effect of growth hormone was determined with tetracycline as intravital marker of the longitudinal bone growth of proximal tibia in female Sprague-Dawley rats hypophysectomized at 60 days of age. After a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. L-thyroxine was given in association with the growth hormone administration to potentiate the growth stimulation. A linear log dose-response relation was found for the two administration models with a high precision. The thyroxine-treatment increased the sensitivity of the bioassay. An administration period of 5 days was found sufficient for the bioassay of growth hormone in thyroxine-treated hypophysectomized rats. Compared with the earlier bioassay methods for growth hormone, the present bioassay is more favourable when all the factors, such as precision, sensitivity, specificity, and administration period are considered.

scholarly journals Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Li Lu ◽  
Huang Zhijian ◽  
Li Lei ◽  
Chen Wenchuan ◽  
Zhu Zhimin
Keyword(s):  
Combined Treatment ◽  
Insulin Injection ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Titanium Implants ◽  
Sprague Dawley ◽  
Machined Surface ◽  
Double Labeling ◽  
The Right ◽  
Cp Ti

This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed.

scholarly journals Successful Combined Treatment for Atrophic Thyroiditis With Growth Hormone Deficiency

2016 ◽  
Vol 3 ◽  
pp. 2333794X1667008
Author(s):  
Taketo Otsuka ◽  
Naoya Tajima ◽  
Keisuke Nagasaki ◽  
Minoru Okazaki
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Combined Treatment ◽  
Hormone Deficiency

scholarly journals Gut microbiota induce IGF-1 and promote bone formation and growth

2016 ◽  
Vol 113 (47) ◽  
pp. E7554-E7563 ◽  
Author(s):  
Jing Yan ◽  
Jeremy W. Herzog ◽  
Kelly Tsang ◽  
Caitlin A. Brennan ◽  
Maureen A. Bower ◽  
...  
Keyword(s):  
Bone Formation ◽  
Gut Microbiota ◽  
Bone Mass ◽  
Bone Growth ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Skeletal Growth ◽  
Microbial Colonization ◽  
Adult Mice ◽  
Specific Pathogen

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.

scholarly journals Carcinogenicity Assessment of Daprodustat (GSK1278863), a Hypoxia-Inducible Factor (HIF)-Prolyl Hydroxylase Inhibitor

2019 ◽  
Vol 48 (2) ◽  
pp. 362-378 ◽  
Author(s):  
David F. Adams ◽  
Mark S. Watkins ◽  
Luc Durette ◽  
Josée Laliberté ◽  
Félix Goulet ◽  
...  
Keyword(s):  
Cell Mass ◽  
Hypoxia Inducible Factor ◽  
Carcinogenic Risk ◽  
Prolyl Hydroxylase ◽  
High Dose ◽  
Sprague Dawley ◽  
Time Curve ◽  
Clinical Exposure ◽  
High Doses ◽  
Hif Prolyl Hydroxylase

Daprodustat (GSK1278863) is a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor in development for treatment of anemia of chronic kidney disease. Daprodustat’s biological activity simulates components of the natural response to hypoxia; inhibition of PHDs results in HIF stabilization and modulation of HIF-controlled gene products, including erythropoietin. The carcinogenic potential of daprodustat was evaluated in 2-year carcinogenicity studies in Sprague-Dawley rats and CD-1 mice, where once-daily doses were administered. The mouse study also included evaluation of daprodustat’s 3 major circulating human metabolites. There were no neoplastic findings that were considered treatment related in either study. Exaggerated pharmacology resulted in significantly increased red cell mass and subsequent multiorgan congestion and secondary non-neoplastic effects in both species, similar to those observed in chronic toxicity studies. In rats, these included aortic thrombosis and an exacerbation of spontaneous rodent cardiomyopathy, which contributed to a statistically significant decrease in survival in high-dose males (group terminated in week 94). Survival was not impacted in mice at any dose. Systemic exposures (area under the plasma concentration–time curve) to daprodustat at the high doses in rats and mice exceed predicted maximal human clinical exposure by ≥143-fold. These results suggest that daprodustat and metabolites do not pose a carcinogenic risk at clinical doses.

Opposite effects of growth hormone and estrogens on the pregnancy zone protein serum levels in children and adolescents

1993 ◽  
Vol 128 (4) ◽  
pp. 334-338 ◽  
Author(s):  
K Devriendt ◽  
G Massa ◽  
F de Zegher ◽  
M Vanderschueren-Lodeweyckx ◽  
JJ Cassiman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Turner Syndrome ◽  
Recombinant Human Growth Hormone ◽  
Serum Levels ◽  
Hormone Deficiency ◽  
Normal Range ◽  
Protein Levels ◽  
Pregnancy Zone Protein ◽  
Protein Serum

Serum levels of pregnancy zone protein were measured in children with growth hormone deficiency and in girls with Turner syndrome, before and during treatment with recombinant human growth hormone and in healthy controls. The pregnancy zone protein serum levels in growth hormone deficiency patients before treatment were significantly higher than in controls (median value 2420 μg/l vs 434 μg/l; p≤0.001). In Turner syndrome patients they were within the normal range. The administration of rhGH to both growth hormone deficiency and Turner syndrome patients resulted in a significant decrease in the serum pregnancy zone protein levels by approximately 50%. The addition of 50 ng·kg−1·d −1 ethinylestradiol to the growth hormone treatment in Turner syndrome patients led to an increase in pregnancy zone protein concentrations in four out of five patients. Elevated pregnancy zone protein levels were also found in two children with growth hormone resistance (Laron type dwarfism). In one patient with placental growth hormone deficiency, pregnancy zone protein serum levels during pregnancy were within the normal range. These results suggest that the serum pregnancy zone protein levels are down-regulated by growth hormone.

Erythropoietin and Cyclophosphamide Combined Treatment Additively Enhances Immunoglobulin Production in Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4913-4913
Author(s):  
Lilach Lifshitz ◽  
Assaf Berger ◽  
Maayan Avneon ◽  
Moshe Mittelman ◽  
Drorit Neumann
Keyword(s):  
Humoral Immunity ◽  
Combined Treatment ◽  
Humoral Response ◽  
Serum Levels ◽  
Immunosuppressive Agent ◽  
Immunoglobulin Production ◽  
Humoral Immune ◽  
C57bl Mice ◽  
High Doses ◽  
Cancer Related Anemia

Abstract Erythropoietin (EPO) is an important component in the treatment of cancer patients for improvement of cancer related anemia. EPO treatment for cancer related anemia is usually combined with chemotherapy. Cyclophosphamide (CP) is a known cytotoxic alkylating agent widely used in cancer chemotherapy. While at high doses it functions as an immunosuppressive agent, the anti-neoplastic activities of CP at low doses are attributed to enhancement of cellular and humoral immunity e.g. (Berd et al., Cancer Res; 1984). We have previously shown that EPO displays anti-neoplastic activities (Mittelman, 2001, 2004) and that EPO treatment is associated with enhancement of both the humoral and cellular immune responses (Prutchi-Sagiv 2006, Katz 2007). Here we focused on a murine model of DNP-KLH-injection, used to assess the humoral response in mice. Recently we demonstrated that administration of high doses of EPO (180U×3) to DNP-KLH-injected C57BL mice resulted in an increase in anti-DNP immunoglobulin G1 (IgG1) production. The present study was designed to examine the effect of combining low dose CP (12.5mg/kg ×2) used to achieve an anti-neoplastic activity, with a lower dose of recombinant human EPO (rHuEPO; 90U×3) on the humoral immune response of the DNP-KLH-injected mice, thus simulating the conditions of patient care. Hence, we compared anti-DNP Ig serum levels in DNP-KLH-injected C57BL mice that were treated with either EPO or CP alone, or the combination of CP and EPO (CP-EPO). CP treatment alone resulted in increased levels of serum anti-DNP IgG1 (O.D.(CP) = 0.38±0.06 vs O.D.(Non treated) = 0.18±0.064). In contrast, EPO treatment alone enhanced serum levels of IgG2 (O.D.(EPO) = 0.47±0.09 vs O.D.(Non treated) = 0.18±0.069). CP or EPO alone did not affect the total levels of anti-DNP total Ig (O.D.(EPO) = 0.37±0.07 vs O.D.(Non treated) = 0.28±0.04). Yet, the combined CP-EPO treatment resulted in increased levels of anti-DNP total Ig (O.D.(EPO+CP) = 0.48±0.05 vs O.D.(EPO or CP) = 0.37±0.04), maintaining the higher levels of IgG1 (O.D.(EPO+CP) = 0.38±0.06) and IgG2 (O.D.(EPO+CP) = 0.49±0.1). In summary, the combined CP-EPO treatment additively improved immunoglobulin production, compared to treatment with CP or EPO alone. We thus demonstrate that in context of chemotherapy treatment as usually administered in the clinic, EPO can enhance humoral immunity alongside its erythropoietic activities. Our findings emphasize the role of EPO as an immunomodulator, particularly when given as treatment in a combined therapeutic panel

Sign in / Sign up

Export Citation Format

Share Document