Adjudin is a drug that inhibits cell adhesion between sertoli cells and maturing sperm cells. Sertoli cells play an important role in Spermatogenesis. The Sertoli cells are pyramid shaped and line the seminiferous tubules with their bases bound to the basement membrane of the tubule. Spermatogenic cells are embedded in the membrane of the Sertoli cells, which provide nutritive support to the maturing sperm (Jones and Lopez). If the sperm cell loses contact with the Sertoli cell before it has fully matured it is considered infertile. Adjudin is an analogue of indazole-carboxylic acid, which is a chemotherapeutic agent. By binding Adjudin to a recombinant follicle stimulating hormone (FSH) mutant the specificity to attack only Sertoli-spermatogenic cell adhesions is possible (Mruk et al.). The mutant FSH molecule was still capable of binding to Sertoli cells and did not bind stimulate inhibin B production. Inhibin B is a peptide that inhibits FSH production by not allowing GnRH release from the hypothalamus (Activin and Inhibin). This is important because if GnRH is inhibited that inhibits testosterone and will reduce secondary sexual characteristics, a side effect that must not be present for the drug to be a success.
Early research looked at oral administration of the drug but it was quickly recognized this resulted in liver inflammation and muscle atrophy (Mruk). Looking at rat tissue samples from the kidney, liver, brain, heart, epididymis, prostate and seminal vesicles showed that there was no deteriation in the cell adhesions of each organ when the Adjudin-FSH mutant is administered intravenously (Mruk et al.). This new model of Adjudin now only targets the specific cell adhesions between Sertoli cells and sperm, unlike the earlier orally administered drug which effected the body throughout. Demonstrating the low bioavailability of Adjudin it would be necessary for an implant to be used so that there would be no degradation done by the digestive system (Connor). Another possible avenue being looked at is to make the drug into a topical cream that is applied to the scrotum (malecontraceptives). The hope is the drug would be absorbed through the skin and act locally on the testicles.
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