iturelix and Body-Weight

To investigate the influence of phyotestrogens in the diet, an immature uterotrophic assay of ethinylestradiol, bisphenol A, 4-nonylphenol or genistein was performed in rats given the formula MF diet, modified NIH-07 open formula diet, or modified NIH-07 phytoestrogen-lowered-diet (study 1). The chemicals were administered subcutaneously from 20 days of age for 3 days. Doses of ethinylestradiol, bisphenol A, 4-nonylphenol or genistein were 0.06-0.6 micro g/kg per day, 1-10 mg/kg per day, 10-100 mg/kg per day or 1-20 mg/kg per day, respectively. In another study, an immature uterotrophic assay of genistein and ethinylestradiol together with ICI 182,780 or antide was performed to compare the ovarian changes with these chemicals (study 2). Doses of genistein or ethinylestradiol were 30 mg/kg per day or 0.6 micro g/kg per day, respectively, and these chemicals were injected subcutaneously from 20 days of age for 3 days. In study 1, there were no essential differences in the uterus weights among the various phytoestrogen-content diets. In study 2, the ovary weights in rats given genistein were significantly higher than in the controls, whereas the ovary weights in rats given ethinylestradiol were lower than in the controls. The ovary weights in the ICI 182,780 plus genistein group were significantly higher than in the genistein group, but decrease of the ovary weights was detected in the antide plus genistein group. There was no significant difference in ovary weights between the ICI 182,780 plus ethinylestradiol group and the ethinylestradiol group, but decrease of ovary weights was detected in antide plus ethinylestradiol group. In a histological examination of the ovary, fluid-filled follicles in the genistein group were more numerous than in other groups and increase of granulosa cell fragmentation was seen in the ethinylestradiol and other groups with the exception of the genistein group. The present findings demonstrate that the sensitivity of the immature rat uterotrophic assay is not influenced by the relatively low level of phytoestrogen in diets and that the ovarian changes occurring with genistein and ethinylestradiol are different.

Topics: Animals; Benzhydryl Compounds; Body Weight; Dose-Response Relationship, Drug; Estradiol; Estrogens, Non-Steroidal; Ethinyl Estradiol; Female; Fulvestrant; Genistein; Isoflavones; Oligopeptides; Organ Size; Ovary; Phenols; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Uterus

In a 5-year longitudinal study, we examined the effect of disrupting the neonatal activity of the pituitary-testicular axis on the sexual development of male rhesus monkeys. Animals in a social group under natural lighting conditions were treated with a GnRH antagonist (antide), antide and androgen, or both vehicles, from birth until 4 months of age. In antide-treated neonates, serum LH and testosterone were near or below the limits of detection throughout the neonatal period. Antide + androgen-treated neonates had subnormal serum LH, but above normal testosterone concentrations during the treatment period. From 6 to 36 months of age, serum LH and testosterone were near or below the limits of detection. Ten of 12 control animals reached puberty during the breeding season of their 4th year, compared with five of 10 antide- and three of eight antide + androgen-treated animals. Although matriline rank was balanced across treatment groups at birth, a disruption within the social group during year 2 resulted in a marginally lower social ranking of the two treated groups compared with the controls. More high (78%) than low (22%) ranking animals reached puberty during year 4. During the breeding season of that year, serum LH, testosterone and testicular volume were positively correlated with social rank. Thus the lower social rank of treated animals may have contributed to the subnormal numbers of these animals reaching puberty during year 4. However, of those animals achieving puberty during year 4, the pattern of peripubertal changes in serum testosterone and testicular volume differed between control and antide-treated animals. The results appear to suggest that the disruption of normal activity of the neonatal pituitary--testicular axis retarded sexual development, but that social rank is a key regulatory factor in setting the timing of sexual maturation in male rhesus monkeys. The effect of neonatal treatment with antide and low social rank on sexual development could not be reversed by neonatal exposure to greater than normal concentrations of androgen.

Topics: Analysis of Variance; Animals; Animals, Newborn; Body Weight; Gonadotropin-Releasing Hormone; Hierarchy, Social; Hormone Antagonists; Luteinizing Hormone; Macaca mulatta; Male; Oligopeptides; Organ Size; Sexual Maturation; Testis; Testosterone

The ability of a long-acting androgen, testosterone buciclate (TB), to induce suppression of testicular and epididymal sperm functions when given in combination with a potent GnRH antagonist (Antide) either on day 1 or 45 of Antide administration (days 1-90) as well as the ability of TB to maintain Antide-induced suppression of spermatogenesis were evaluated in adult bonnet monkeys. A group of untreated animals (group I) acted as controls. All animals given Antide and androgen simultaneously (group II) became azoospermic but at different times. When androgen administration was delayed 45 days after start of Antide treatment (group III), the mean sperm concentration remained in the normospermic range and only three animals became azoospermic. Antide given alone (group IV) induced azoospermia in three animals and oligospermia in the remaining animals; spermatogenesis recovered when Antide was withdrawn and TB was injected. In all Antide-treated animals (groups II-IV), non-motile spermatozoa or sperm with non-progressive motility and poor gel penetrability were seen in the ejaculate.

Topics: Animals; Body Weight; Contraceptive Agents, Male; Ejaculation; Epididymis; Gonadotropin-Releasing Hormone; Hormone Antagonists; Macaca radiata; Male; Oligopeptides; Sperm Motility; Spermatogenesis; Spermatozoa; Testosterone

GnRH antagonists have potential for use in postpartum contraception, as it is likely that they would be effective in maintaining the inhibition of ovulation associated with lactation, but possible effects on the infant by transfer of antagonist via breast milk are unknown. The aim of this study was to establish whether chronic treatment with a GnRH antagonist would prevent ovulation throughout the period of lactation using the marmoset monkey as a model and to evaluate the effects of the presence of GnRH antagonist in breast milk on the postnatal rise in plasma testosterone concentrations in male infants. Mothers who had delivered male twins were selected. Starting within 3 days postpartum, mothers (n = 5/group) were treated with either 6.0 or 0.6 mg/kg of the GnRH antagonist antide, sc, once per week for 11 weeks. Ten postpartum lactating females acted as controls. All animals were housed in family groups with fertile males. To determine possible effects on the postnatal rise in testosterone, plasma samples were collected from the male infants of the high dose antide-treated mothers at weekly intervals for 12 weeks. Plasma progesterone concentrations were monitored in lactating mothers until establishment of pregnancy in both treated and control groups. Concentrations of antide were determined by RIA in plasma from mothers in the high dose group, in their milk, and in pooled plasma samples from their infants. Ovulation followed by pregnancy occurred in all of the control animals. No ovulations occurred during treatment with antide. Antide was present throughout treatment in plasma and breast milk in the mother. In male infants feeding from mothers receiving high dose treatment, antide was not detectable in infant plasma, and plasma testosterone concentrations were within the normal range for male neonates in our colony. These results indicate that the GnRH antagonist has potential as a method of contraception postpartum without affecting the postnatal rise in testosterone in male infants.

Topics: Animals; Animals, Newborn; Body Weight; Callithrix; Contraception; Female; Gonadotropin-Releasing Hormone; Lactation; Male; Milk; Oligopeptides; Osmolar Concentration; Ovulation; Postpartum Period; Pregnancy; Pregnancy Outcome; Sex Characteristics; Testosterone