RESUMO
The use of gonadotrophins for the treatment of infertility began in the 1930s following early work on the pituitary-ovarian axis and the discovery of FSH and LH. The technological development of pharmaceutical gonadotrophins over the last 40 years has shown improvements in specific activity, purity, degradation and impurities. Throughout these pharmaceutical developments the gonadotrophin content of both urinary and recombinant preparations has been assessed using an animal in-vivo bioassay. This paper reflects upon the manufacturing history of recombinant human FSH (r-hFSH) and follitropin alfa filled by mass (FbM), and evaluates the impact of introducing a pharmaceutical product that is formulated and assayed by a physicochemical method for r-hFSH protein content. It also compares the analytical consistency of follitropin alfa FbM with another commercially available r-hFSH, follitropin beta.
Assuntos
Hormônio Foliculoestimulante/análise , Subunidade alfa de Hormônios Glicoproteicos/análise , Infertilidade Feminina/tratamento farmacológico , Bioensaio , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Feminino , Hormônio Foliculoestimulante/história , Hormônio Foliculoestimulante/uso terapêutico , Subunidade beta do Hormônio Folículoestimulante/análise , Subunidade alfa de Hormônios Glicoproteicos/história , Subunidade alfa de Hormônios Glicoproteicos/uso terapêutico , História do Século XX , História do Século XXI , Humanos , Polissacarídeos/metabolismo , Isoformas de Proteínas/análise , Controle de QualidadeRESUMO
To test the hypothesis that growth hormone (hGH) may increase adrenal androgen production dehydroepiandrosterone (DHA) and its sulphate (DHAS) concentrations were measured by radioimmunoassay in the serum from 7 children with growth hormone deficiency, 2 of whom had delayed puberty. Two injections of hGH (10 mg) were given 48 h apart and the hormone concentrations measured at 3, 6, 24 and 48h after the first injection, 3, 6, and 24h after the second. Basal DHA levels were positively correlated with age and bone age in 6 of the 7 patients (p less than 0.05). Increment of DHA and DHAS above or below basal at each time interval were calculated. The mean increments were higher (p less than 0.01-0.05) at 3 h after the first injection and at 24h (p lesal DHA concentrations were positively correlated with increments in DHA during the first and second 24h of the test (p less than 0.05). DHAS concentrations showed little change throughout the test for all children. It is suggested that some children with growth hormone deficiency and receptive adrenals, increase their serum DHA concentrations after acute hGH therapy.
