Consensus ; Growth Disorders ; diagnosis ; drug therapy ; Hormone Replacement Therapy ; Human Growth Hormone ; administration & dosage ; deficiency ; therapeutic use ; Humans ; Practice Guidelines as Topic

PURPOSE: Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS AND METHODS: The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects. RESULTS: Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression. CONCLUSION: Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.
Administration, Oral ; Animals ; Body Weight ; Growth Hormone* ; Growth Plate ; Hypothalamus ; Insulin-Like Growth Factor I ; Pituitary Gland ; Rats* ; RNA, Messenger ; Somatostatin ; Tibia

Anorexia is one of the most common issues in older patients. Although there is a tendency for loss of appetite in older persons due to decreased physical activity and reduced resting metabolic rate, this physiological anorexia of aging can easily develop into progressive anorexia and weight loss. This pathologic anorexia and resultant weight loss is associated with increased morbidity and mortality, especially in the frail elderly. To prevent older persons from entering a vicious cycle of frailty, that is, anorexia-malnutrition-sarcopenia-functional impairment, routine screening for anorexia and malnutrition should be implemented in geriatric clinical practice. All anorexic elderly patients should be strongly encouraged to maintain their nutrition, and appetite stimulants can be considered if non-pharmacological interventions are not effective. Although there are no US or Korea Food and Drug Administration approved medications for geriatric-specific anorexia and weight loss, several appetite stimulants can be prescribed and are used widely. Megestrol acetate is the most widely studied and commonly used of these drugs. Cyproheptadine, dronabinol, mirtazapine, corticosteroids, anabolic steroids (e.g., testosterone or oxandrolone), and growth hormone are also effective in increasing appetite or weight. However, the use of these orexigenic agents should occur only after their benefit-to-risk ratio has been carefully considered.
Adrenal Cortex Hormones ; Aged ; Aging ; Anorexia ; Appetite Stimulants* ; Appetite* ; Cyproheptadine ; Diethylpropion ; Dronabinol ; Frail Elderly ; Growth Hormone ; Humans ; Korea ; Malnutrition ; Mass Screening ; Megestrol Acetate ; Mortality ; Motor Activity ; Steroids ; Testosterone ; United States Food and Drug Administration ; Weight Loss

PURPOSE: The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage(TM)) supplement in patients with growth hormone deficiency were evaluated. MATERIALS AND METHODS: This trial is 12-week prospective, single-arm, open-label trial. Men and women aged > or =20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. RESULTS: The IGF-1 level of 108.67+/-74.03 ng/mL was increased to 129.01+/-68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80+/-6.51 to 7.55+/-5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. CONCLUSION: Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.
Adult ; Aged ; Delayed-Action Preparations ; Female ; Growth Hormone/administration & dosage/*adverse effects/*therapeutic use ; Human Growth Hormone/*deficiency ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recombinant Proteins/administration & dosage/*adverse effects/*therapeutic use

Body Height ; drug effects ; Child ; Drug Monitoring ; Growth Disorders ; diagnosis ; drug therapy ; Human Growth Hormone ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Practice Guidelines as Topic ; Recombinant Proteins ; administration & dosage ; adverse effects ; therapeutic use ; Risk Factors

OBJECTIVETo evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.

METHODSixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.

RESULT(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.

CONCLUSIONIntermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.

Body Height ; drug effects ; Bone Development ; Child ; Child Development ; drug effects ; Drug Therapy, Combination ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; therapeutic use ; Growth Disorders ; drug therapy ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology ; Stanozolol ; administration & dosage ; therapeutic use ; Treatment Outcome

This study is to explore the effects of quercetin (QUE) on the 3 week-old mice ovarian development and relative hormone levels. The 3 week-old mice were exposed to QUE (45, 25, and 5 mg x kg(-1) x hd(-1)) by gavage for 50 days. The estrous cycle during 50 days and the changes of hormone level such as FSH, LH, etc were monitored. Moreover, the ovaries were removed after sacrifice. The organ index was measured, and the ratios of different stages of follicles were analyzed by HE staining. Furthermore, the proportion of PCNA positive cells during all stages was detected by immunohistochemistry. The results showed that QUE could increase body weight of mice and reduce the anogenital distance (AGD) to some extent, and was able to disrupt mice's estrous cycle, but it could not extend or reduce the cycle regularity. It increased ovarian organ index with a dose-dependent manner. The proportion of the primordial follicle and secondary follicles rose obviously, and that of mature follicles', atretic follicles' and corpus luteums' reduced, while primordial follicle had no change. Immunohistochemistry analysis showed that QUE could effectively increase the percentage of proliferating cells in all kinds of follicles. Serum hormone assay showed that there were significant changes of FSH and LH levels. In summary, QUE showed an estrogen-like effect on mice's ovarian development. The weight of ovary, the proportion of all kinds of follicles, the development of ovarian cells and the level of plasma hormone in mice were altered obviously by oral administration of QUE.
Animals ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Estrous Cycle ; drug effects ; Female ; Follicle Stimulating Hormone ; blood ; Luteinizing Hormone ; blood ; Mice ; Ovarian Follicle ; drug effects ; metabolism ; Ovary ; drug effects ; growth & development ; Phytoestrogens ; administration & dosage ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Quercetin ; administration & dosage ; pharmacology ; Random Allocation

Human Growth Hormone ; administration & dosage ; pharmacology ; Recombinant Proteins ; administration & dosage ; pharmacology

In a rabbit model of collagenase-induced osteoarthritis, the additive effects of intra-articular recombinant human growth hormone (GH) administration to hyaluronic acid (HA) were evaluated. After intra-articular collagenase injection, mature New Zealand white rabbits (n=30) were divided into 3 groups. Group 1 (control rabbits) received once weekly intra-articular saline injections for 4 weeks. Group 2 rabbits received 6 mg HA injections, and group 3 rabbits were injected with 6 mg HA and 3 mg recombinant human GH. These injections were initiated 4 weeks after collagenase injections. Lameness was observed for 9 weeks after collagenase injections. Macroscopic and histopathological knee joint findings were also evaluated at the end of 9 weeks after collagenase injections. Although all animals had lameness after collagenase injections, the duration and severity of lameness were significantly shorter and less severe in group 3 than group 1 and 2 (P<0.01). Macroscopic scores showed that femoral condyles of group 3 rabbits received significantly less cartilage damage than those of groups 1 and 2 rabbits (P<0.01). Histopathological score was also the lowest in group 3 (P<0.01). These results suggest that co-injection of intra-articular HA and recombinant human GH is more effective than HA injections alone in an osteoarthritis model.
Animals ; *Collagenases ; *Disease Models, Animal ; Drug Combinations ; Drug Synergism ; Human Growth Hormone/*administration & dosage ; Humans ; Hyaluronic Acid/*administration & dosage ; Injections, Intra-Articular ; Male ; Osteoarthritis/*chemically induced/diagnosis/*drug therapy ; Rabbits ; Treatment Outcome

BACKGROUNDExperimental studies and preliminary clinical studies have suggested that growth hormone (GH) treatment may improve cardiovascular parameters in chronic heart failure (CHF). Recombinant human GH (rhGH) has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles (BAMs), and investigate whether the rhGH delivered by this technique improves left ventricular (LV) function in rats with CHF.

METHODSPrimary skeletal myoblasts were isolated from several Sprague-Dawley (SD) rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups: CHF control group (n = 6) and CHF treatment group (n = 6). The CHF control group received non-rhGH-secreting BAM (GFP-BAMs) transplantation, and the CHF treatment group received rhGH-secreting BAM (GH-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: sham control group (n = 6) and sham treatment group (n = 6). The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligation of the left coronary artery or sham operation was performed. Eight weeks after the treatment, echocardiography was performed. hGH, insulin-like growth factor-1 (IGF-1) and TNF-alpha levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry.

RESULTSPrimary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 1 to 2 microg of bioactive rhGH per day. When implanted into syngeneic rat, GH-BAMs secreted and delivered rhGH. Eight weeks after therapy, LV ejection fraction (EF) and fractional shortening (FS) were significantly higher in CHF rats treated with GH-BAMs than in those treated with GFP-BAMs ((65.0 +/- 6.5)% vs (48.1 +/- 6.8)%, P < 0.05), ((41.3 +/- 7.4)% vs (26.5 +/- 7.1)%, P < 0.05). LV end-diastolic dimension (LVEDD) was significantly lower in CHF rats treated with GH-BAM than in CHF rats treated with GFP-BAM (P < 0.05). The levels of serum GH and IGF-1 were increased significantly in both CHF and sham rats treated with GH-BAM. The level of serum TNF-alpha decreased more significantly in the CHF treatment group than in the CHF control group.

CONCLUSIONSrhGH significantly improves LV function and prevents cardiac remodeling in rats with CHF. Genetically modified tissue-engineered bioartificial muscle provides a method delivering recombinant protein for the treatment of heart failure.

Animals ; Bioartificial Organs ; Echocardiography ; Heart Failure ; therapy ; Human Growth Hormone ; administration & dosage ; Myoblasts, Skeletal ; metabolism ; Myocardial Infarction ; pathology ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; Tissue Engineering ; Tumor Necrosis Factor-alpha ; blood ; Ventricular Function, Left