General pharmacology studies on recombinant human follicle stimulating hormone.

Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein secreted by anterior pituitary cells. Its main actions are to lead ovarian follicles to maturation and to maintain spermatogenesis. Up to now the FSH preparations used in clinical practice (CAS 9002-68-0 and CAS 97048-13-0) have been purified from human postmenopausal urine. Only recently, a product was successfully obtained by recombinant-DNA technology, r-hFSH (Gonal-FTM). This recombinant protein is highly pure and has a very high specific activity. In view of its clinical use, this hormone has been submitted to an extensive panel of general pharmacology studies with the aim of defining its pharmacological profile and determine possible side effects not related to the main therapeutic action. Subcutaneous or intravenous doses of 5 to 500 IU/kg were assayed in several tests for their effects in vivo on various systems in different animal species. The substance under study was also tested in vitro on isolated guinea-pig ileum preparations at final concentrations of 0.05 to 2 IU/ml of bath. The results of this study showed that r-hFSH does not influence the general activity and behaviour of mice, as measured by the multidimensional Irwin's test. Similarly, the drug was not found to affect the normal body temperature in rats nor the locomotor activity in mice for as long as 7 h post-injection; in addition, it was not found to induce pharmacologically significant alterations of the cardiovascular and respiratory parameters in rats and dogs.(ABSTRACT TRUNCATED AT 250 WORDS)