Effects of constant infusion with insulin-like growth factor-I (IGF-I) to immature female rats on body weight gain, tissue growth, and sexual function: Evidence that such treatment does not affect sexual maturation or fertility

Plasma levels for insulin-like growth factor-I (IGF-I) steadily increase in female rats between 20 and 40 d of life, and this increase is intimately related to the wellknown growth spurt occurring at this age. Since specific actions of IGF-I related to sexual function have been described at the ovarian and hypothalamic levels, an endocrine role of rising circulating IGF-I levels during sexual maturation cannot be excluded. Therefore, the impact of adult-type plasma IGF-I levels during the juvenile age, on body weight (BW) gain, growth of several organs, sexual development, and fertility has been evaluated. Female Sprague-Dawley rats were infused with rhIGF-I (2 and 4 μg/g BW/d, using Alzet minipumps), between 20 and 41 d of life. When infusing 2 μg/g BW/d, plasma levels for IGF-I were increased 1.5- to 2-fold over controls at all ages studied. They were further increased with the higher dosage, but only after 35 d of age. Plasma levels for insulin-like growth factor binding protein (IGFBP)-1 to-3 were clearly increased. BW gain was significantly increased, but only with the higher dosage. Tail length was never modified. In contrast, a growth acceleration for spleen, kidneys, adrenals, and ovaries was observed with both dosages. The ovarian weight of treated animals represented approx 140% of control animals with the 4 μg/g BW/d dosage. Histology of the enlarged ovaries did not reveal any abnormalities. No meaningful modification of the timing of vaginal opening was observed, and fertility was not compromised by previous rhIGF-I infusion during the 20-41 d age period. In summary, early exposure to increased (adult-like) plasma IGF-I levels did not modify BW gain or tail length, but affected the development of spleen, kidneys, adrenals, and ovaries. Exposure to supraphysiological plasma IGF-I levels (>1200 ng/mL), accelerated BW gain and increased the weight of all organs studied. No signs of precocious sexual maturation were seen and fertility was normal. In conclusion, prematurely increased plasma IGF-I levels affected somatotropic parameters, but not the onset of sexual functio

Biological characterization of purified native 20-kDa human growth hormone

Because of the propensity of the 20-kDa variant of human growth human (GH) to aggregate with itself and with 22-kDa human GH, it has been difficult to prepare monomeric 20-kDa GH in highly purified form. This has been a major complicating factor in determining whether 20-kDa GH has a biological activity profile distinct from that of 22-kDa GH. In the present study, native 20-kDa GH was isolated from a human GH dimer concentrate and purified by a procedure that included column electrophoresis in agarose suspension as a final separation step. This procedure yielded highly purified monomeric 20-kDa GH, which was contaminated to an extent of less than 1% with 22-kDa GH, and which exhibited only a small degree of dimerization upon storage. The native 20-kDa Gh was quite active in stimulating growth in hypophysectomized rats, when growth was assessed by body weight gain, longitudinal bone growth, the stimulation of sulfation of cartilage, and the elevation of serum IGF-1 level. However, in all of these growth assays, the 20-kDa GH was somewhat less active than the native 22-kDa GH to which it was compared; e.g., in the body weight gain and longitudinal bone growth assays, it had an estimated potency of 0.6 relative to the 22-kDa GH. The 20-kDa GH exhibited substantial diabetogenic activity when tested for the ability to raise fasting blood glucose concentration and to impair glucose tolerance in ob/ob mice. Also, the native 20-kDa GH had significant in vitro insulin-like activity, although its potency was approximately 20% that of the native 22-kDa GH to which it was compared. Thus, the biological activity profile of native 20-kDa GH differs from that of 22-kDa GH primarily in that insulin-like activity is markedly attenuated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26576/1/0000115.pd

Alternative therapies for symptom management in fibromyalgia : a literature review

Bakgrund Sjukdomen fibromyalgi drabbar i genomsnitt två procent av befolkningen i varje land och 90 procent av de insjuknade är kvinnor. Fibromyalgi kan debutera i alla åldrar och ännu finns ingen effektiv metod för att bota sjukdomen. De främsta symtomen vid fibromyalgi är generell och ständig värk som flyttar runt i kroppen samt en onormal trötthet och kraftlöshet. Depression är också ett vanligt symtom hos personer med fibromyalgi. Många personer med fibromyalgi väljer att använda sig av icke farmakologiska behandlingar för att lindra sina symtom. Kombinationen mellan farmakologisk behandling för exempelvis sömnproblem tillsammans med icke farmakologiska behandlingar som fysisk aktivitet och akupunktur har visats sig ha god effekt. Sjukvårdens tro på alternativa behandlingsmetoder är, och har tidigare visat sig, svag trots att forskning visar på tillfredsställande symtomlindring vid icke farmakologisk behandling. Syfte Syftet var att utvärdera effekten av icke farmakologiska behandlingsmetoder för symtomlindring hos personer med fibromyalgi. Metod Metoden som användes för att svara på syftet var litteraturöversikt. Artiklar söktes i databaserna PubMed och CINAHL. Litteraturöversikten innefattar 16 artiklar. Resultat De icke farmakologiska metoderna som utvärderades var akupunktur, qigong, massage och fysisk aktivitet. Alla metoder visade sig ha god effekt på reducerad smärta, antal smärtpunkter, ångest samt depression. Qigong och massage visade sig även förbättra sömnkvalitén. Fysisk aktivitet och massage ökade även den fysiska funktionen. Slutsats De icke farmakologiska metoderna akupunktur, qigong, massage och fysisk aktivitet har alla visat positiv effekt för symtomlindring hos personer med fibromyalgi

A novel dysfunctional growth hormone variant (Ile179Met) exhibits a decreased ability to activate the extracellular signal-regulated kinase pathway

The pituitary-expressed GH1 gene was screened for mutation in a group of 74 children with familial short stature. Two novel mutations were identified: an Ile179Met substitution and a -360AG promoter variant. The Ile179Met variant was shown to exhibit a similar degree of resistance to proteolysis as wild-type GH, indicating that the introduction of Met does not cause significant misfolding. Secretion of Ile179Met GH from rat pituitary cells was also similar to that of wild type. Although receptor binding studies failed to show any difference in binding characteristics, molecular modeling studies suggested that the Ile179Met substitution might nevertheless perturb interactions between GH and the GH receptor loop containing the hotspot residue Trp169, thereby affecting signal transduction. The ability of the Ile179Met variant to activate a signal transducer and activator of transcription (STAT) 5-responsive luciferase reporter gene and induce phosphorylation of STAT 5 and ERK was therefore studied. In contrast to its ability to activate STAT 5 normally, activation of ERK by the Ile179Met variant was reduced to half that observed with wild type. Although differential effects on the activation of distinct signaling pathways by a mutant receptor agonist are unprecedented, these findings also suggest that the ERK pathway could play a role in mediating the action of GH