Blood levels of nitric oxide and endothelin-1 during normal menstrual cycle

Nitric oxide [NO] is a free radical gas synthesized from L-arginine by a class of specific enzymes known as NO synthases, and inducible NO synthase isoforms. Nitric oxide synthase activity has been identified in the human uterus and has been thoroughly studied in pregnant women. All three NO synthase isoforms are thought to play an important role in the maintenance of uterine quiescence during gestation, and inducible NO synthase is involved in the induction of cervical ripening before labour. However, few studies have examined the role of NO in the normal menstrual cycle. Endonthelin-1 [ET-1] might play a role in endometrial bleeding and /or repair, as previously reported. In the present study, the serum levels of NO, estradiol [E2] and plasma levels of ET-1 were measured in menstrual follicular and luteal phases of the menstrual cycle to evaluate their role in menstrual cycle. This study included twenty unmarried females with regular menstrual cycles ranging from 27 to 30 days. The levels of serum E[2] and plasma ET-1 were measured by ELISA, and the serum NO were estimated by chemical method. Our results showed that serum levels of E[2] were significantly increased during luteal phase compared with menstrual and follicular phases, whereas plasma levels of ET-1 were significantly higher during menstrual phase compared with follicular and luteal phases of the menstrual cycle. Serum levels of NO did not show significant change during the three phases of the cycle. ET-1 levels were negatively correlated with E[2] while no significant correlation between ET-1 and NO and between NO and E[2]. It can be concluded that ET-1 may play an important role in menstruation and E2 inhibits secretion of ET-1. While NO shows no relation to ET-1 and E[2]

Contraceptive-like effect of melatonin injection in mice

The return of ovulation after melatonin treatment and the possible effects of its administration on some reproductive indices in mice are reported in this study. Admnistration of melatonin in a dose of 4 mg [1 mg/injection] at 1,2,3 and 4 pm on the proestrus phase of the oestrus cycle resulted in - complete inhibition of ovulation during the cycle of melatonin treatment as judged by absence of vaginal plug in the successive 4 days after injection and absence of corpora lutea on the fifth day and by the histological examination of the ovaries which showed the presence of medium sized follicles and absence of corpora lutea. These results showed also that in most animals treated with melatonin inhibited ovulation for one cycle and the animals ovulated in the next cycle after melatonin treatment. The copulatory rate in the first cycle after melatonin treatment for one cycle was 75% and reached 100% in the second cycle. It was also shown from the results of this study that melatonin led to a non significant increase in the duration of the oestrus cycles, no change in the pregnancy rate and overall pregnancy rate and a non significant change in the duration of full term pregnancy and the number of offsprings in comparison with the control animals. It can be concluded that melatonin inhibited ovulation for one cycle. Melatonin proved also to have no adverse effect on many reproductive indices in mice

Ovulatory patterns in female mice following treatment with melatonin

Intraperitoneal injection of melatonin inhibited ovulation in the normal cyclic mice when injected on the proestrus phase. Greater effect was obtained when melatonin was injected at 1,2,3 and 4 pm proestrus day and maximum effect was obtained when the animals were injected with l mg/injection. The administration of melatonin in a dose of 4 mg [1 mg/injection] at 1,2,3 and 4 pm on the proestrus phase of the oestrus cylcle in mice decreased the average number of recent corpora lutea and the average number of lutein cells by 100%. Histological examination of the ovaries of melatonin treated animals showed no evidence of preovulatory swelling of the follicles. Injection of the same dose of melatonin [4 mg] significantly decreased serum proestrus progesterone and oestradiol-17 B level by 2.61% and 29.99% respectively. The serum level of dioestrus progesterone and oestradiol-17 B was significantly decreased by 45.56% and 37.86% respectively. The administration of another low dose [2 mg] led to a weaker effect on the ovary than the highest dose. It can be concluded that melatonin proved to have antiovulatory effect in mice The antiovulatory effect may be due to lowering level of LH either directly - through an inhibitory action on the anterior pituitary gland, or indirectly through either decreasing the secretion of LH releasing hormone from the hypothalamus or decreased levels of serum proestrus progesterone and oestradiol-17 B by direct action on the ovary

Effect of exogenous melatonin on gonadal functions in mature male rats

To study the effect of melatonin on the gonads, seminal vesicles and prostates, melatonin was injected subcutaneously [at 3 p.m] into mature male rats in a dose of 50, 100 and 500 ug. daily for 20 days. A significant decrease [P < 0.01] in the average weight of the testes occurred in the groups treated with the second and third dose of melatonin. A moderate inhibition of spermatogenesis and spermatocytogenesis in most tubules of the testes in the groups treated with lowest dose was observed. Drastic inhibition of spermatogenesis and spermatocytogenesis in the tests of treated groups with the second and third doses was noticed. The number of leydig cells and the diameter of seminiferous tubules were significantly decreased [P < 0.01] in first dose] and [P 0.001 in the second and third doses.] A highly significant decrease [P < 0.001] in the average weights, drastic hypoactive and atrophy of seminal vesicles and prostates in all treated groups was noticed. A significant decrease [P < 0.01] in serum testosterone of the group treated with the lowest dose, and the results of moderate and highest doses were below the sensitivity of the curve [less than 0.3 ng/ml]. From this work, it is clear that the suppressive effects of melatonin on gonadal functions was dose dependant. A maximum inhibitory action resulted from injection of the moderate dose. The suppressive effects of melatonin on gonadal functions may be due to a direct effect on the gonods. Also, may be due to suppression of the gonadotrophin hormone or reduction of the gonadotrophin releasing hormone from the hypothalamus by endorphin. May be also, due to decrease of the prolactin hormone which decreased the sensitivity of LH and FSH receptors in the testes