BLOCKADE OF THE NEONATAL INCREASE IN TESTOSTERONE BY A GNRH ANTAGONIST - THE FREE ANDROGEN INDEX, REPRODUCTIVE CAPACITY AND POSTMORTEM FINDINGS IN THE MALE MARMOSET MONKEY

Male marmoset monkeys which had received gonadotrophin-releasing hormo ne (GnRH) antagonist treatment as neonates to block the postnatal incr ease in testosterone were studied, with the object of determining pote ntial long-term effects of treatment on the reproductive system, inclu ding tests of fertilising capacity. To obtain information on the natur e of the circulating testosterone during this neonatal period, sequent ial blood samples were collected from a further control group of ten n eonates, aged between birth and 3 months, and from 11 adult, normally fertile males, to examine the relative proportions of free, sex-hormon e-binding globulin (SHBG)-bound, and non-SHBG-bound testosterone. In c ontrol neonates, 11% of the circulating testosterone was free, and a f urther 19% non-SHBG-bound, and therefore presumed to be biologically a vailable. The remaining 70% was SHBG-bound and considered to be biolog ically inert. This indicates that the neonatal increase in marmoset te stosterone has a biological function. After pairing with females, time to first positive vaginal lavage and first delivery was similar for f emales, whether they were with control or treated male partners. Pregn ancy outcome, in terms of number of young delivered and sex ratio, did not differ. This indicates that there appear to be no long-term seque lae in terms of procreative ability in male marmosets treated neonatal ly with a GnRH antagonist. Autopsy revealed no gross changes, except i n the thymus, which was significantly heavier in the treated group. Th ese results indicate that, although the circulating testosterone is in a biologically active form during the neonatal period, inhibition of testicular function in the neonate is without major effect on the adul t male reproductive system. Treatment with a GnRH antagonist may have long-term effects on the immune system.