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Bioabsorbable implants prepared by fusion of 85% norethisterone (NET) and 15% cholesterol were inserted subdermally in four cycling bonnet monkeys (Macaca radiata). No skin reaction or inflammation was observed at the site of implantation. Plasma concentration of norethisterone (NET) measured by radioimmunoassay were monitored for 14 to 16 months at monthly intervals. In the first month weekly samples were analysed. NET was released into circulation within 24 hours after insertion of the implant. In all the monkeys, except one, a sharp rise in NET (1.9 to 20 ng/ml) occurred immediately after insertion. Levels then remained between 1.7 and 0.6 ng/ml for about 4 months. Thereafter they remained steady up to about 9 months in two monkeys and gradually declined to about 0.4 ng/ml in the remaining two. In all except one, there was a sudden burst of NET release between the 10th and 11th month. The hormone almost cleared out of circulation by the 14th to 16th month. Initial menstrual cycles after pellet insertion were disturbed, leading to spotting and irregular bleeding. Regular cycles appeared from 5 to 8 months after the insertion of the implant. These cycles were ovulatory, as determined by the progesterone levels.

Binding sites for gonadotropins in the mouse ovary were studied using the immunohistochemical technique. Binding sites for LH were localized in the interstitial cells and theca as well as granulosa cells of large follicles. Binding sites for FSH were demonstrated in the interstitial cells and granulosa cells of small follicles. In immature mice very few binding sites for both the gonadotropins were observed until day 21 of age. An intense staining reaction for peroxidase was observed in the ovary of 24-day old mouse. In adult mice, maximum number of binding sites for FSH were demonstrated in the ovary in estrus and metestrus stage of the cycle, respectively. A good correlation between the circulating levels of gonadotropins and binding sites for them in the ovary could be noted in the cycling but not in the prepubertal mice.

Treatment with RMI 12,936 blocked the mitotic shift from epithelial to stromal cells normally observed in the uterus on Day 4 of pregnancy, and inhibited implantation. While progesterone alone could reverse the change in pattern of cell division in the preparation of the uterus for implantation, both oestradiol and progesterone were necessary to induce implantation and maintain pregnancy. A reduction in the activity of delta 5-3 beta-hydroxysteroid dehydrogenase in the ovaries of RMI 12,936-treated mice suggests that the compound affects luteal synthesis of oestrogen and progesterone in mice.

Mice injected with normal rabbit serum on Day 4 of gestation showed a progressive increase in specific alkaline and acid phosphatase activities on Days 6 and 7. Mice injected with antiserum to LH on Day 4 showed a significant decrease in specific alkaline phosphatase activity estimated biochemically on Days 6, 7 and 8, but this decrease was histochemically evident only on Day 8. Similarly, acid phosphatase activity in antiserum-treated mice was significantly increased on Days 6, 7 and 8 when estimated biochemically, but only on Day 8 when studied histochemically.

A single injection of a 5 alpha-dihydrotestosterone (DHT) was administered to cyclic female mice on the day of metoestrus. DHT (1 mg) prolonged the dioestrous stage of the cycle by 24 h and there were 50% fewer large (normal) follicles than in oil-injected controls. Degenerating ova were observed in the oviduct of 70% of the DHT-treated mice and there was a significant reduction in the numbers of females becoming pregnant and bearing normal fetuses.

Changes in the histopathology of the testes with the epididymis were studied 3 months and 6 months after vasocclusion either with ethanol urea mixture or ethanol alone in male rats. A gradual decrease in the fertility of treated animals was observed. The epididymis showed tubules with sperm granuloma and the testis showed empty tubules with Leydig cell hyperplasia in the urea-ethanol treated animals.

The effect of antisera to ovine LH and ovine prolactin was studied on polyamine levels in the mouse placenta. The antisera were administered on Day 11, 12 or 13 of pregnancy and the mice were killed 24 hr later. The polyamines (spermine, spermidine and putrescine) in the placentae were estimated. Polyamine levels were reduced after treatment with anti-LH on any of the 3 days and after treatment with anti-prolactin serum on Days 11 or 12. Only the spermidine content was reduced when anti-prolactin serum was injected on Day 13 of pregnancy. Placental DNA and RNA levels paralleled those observed for polyamine content. The changes in polyamine content and nucleic acid levels indicate that these antisera to LH and prolactin interfere with placental function.