Blockade of the neonatal rise in testosterone by a gonadotrophin-releasing hormone antagonist: effects on timing of puberty and sexual behaviour in the male marmoset monkey

Abstract

Abstract In primates, plasma testosterone concentrations are elevated for some 3 months from birth. The function of this rise is uncertain, but studies in rats suggest that its prevention by castration or administration of gonadotrophin hormone-releasing hormone (GnRH) analogues has effects on development and expression of social and sexual behaviours, and adverse long-term effects on fertility. The consequences of suppression of this rise in testosterone by treatment with the GnRH antagonist antide have been investigated in the marmoset monkey. Eight sets of male:male twins were used, one of each set receiving s.c. injections of antide (10 mg/kg), on days 0, 3 and 7, then weekly from birth to 98 days of age, with the twin receiving vehicle only. Plasma samples were taken at weekly intervals for the determination of testosterone concentrations from birth until 2 years of age. Treatment with antide completely abolished the neonatal rise in testosterone seen in control animals. The timing of the onset of the pubertal testosterone rise was not significantly affected by treatment; however, the subsequent pattern of circulating testosterone showed a tendency to decreased plasma concentrations in the neonatally treated group from weeks 25 to 42, relative to controls, and this difference was significant between 43 and 70 weeks. This was associated with a similar depression in bioactive LH concentrations around this time. Thereafter, the testosterone concentrations were similar between treated and control groups. There was no effect of treatment on growth, based on sequential body weight data. At 20 months the animals underwent behaviour tests with ovariectomized females. During these encounters, males showed the full panoply of normal sexual behaviours, with response to female proceptivity, tongue flicking, sustainable penile erections, mounts with pelvic thrusting, intromissions and intravaginal ejaculations. No significant differences were observed for any of these parameters between the control and treated animals. No changes in aggressive behaviours between groups were evident. These results show that blockade of the postnatal rise in testosterone in the male marmoset monkey may result in attenuation of the pubertal rise in testosterone but is without major effect on adult basal testosterone concentrations or reproductive behaviour. Journal of Endocrinology (1994) 141, 439–447