Arginine vasotocin: Structure-activity relationships and influence on gonadal growth and function

When AVT (arginine vasotocin) was given neonatally during the period when the brain is undergoing sexual differentiation, increased growth of the reproductive organs was observed in adulthood. Injection of AVT after this neonatal period in immature animals led to diminished growth of the accessory organs and in some cases the gonads themselves. The hypertrophic response of the in situ ovary in adult mice following unilateral ovariectomy (UO) was inhibited in a dose-related manner by a single intraperitoneal injection of freshly prepared AVT. Much less AVT was required for this response when injected into the third ventricle. After intraperitoneal injection, arginine vasopressin (AVP), lysine vasopressin (LVP), and 4-leucine vasotocin (4-leu-AVT) also inhibited compensatory ovarian hypertrophy whereas oxytocin did not. The commonality in die structure of these antigonadotrophic peptides include a closed ring and a basic amino acid in position 8. After opening the disulfide bond of these nonapeptides with mercaptoethanol, a single injection of the reduced AVT, AVP, LVP, or 4-leu-AVT into UO mice causes exaggerated hypertrophy of the remaining ovary. When added with leuteinizing hormone-releasing hormone (LRH) to culture medium containing hemipituitaries from castrated estrogen-progesterone primed female rats, AVT significantly increased the release of radioimmunoassayable LH above that due to LRH alone. AVT might interact at all levels of the hypothalamo-hypophysealgonadal axis.