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Biomedical subjects

I F Lau

Publications and source records attributed to I F Lau.

At least 37 records · Page 2Linked to original sources

Induction of mid-term abortion by trichosanthin in laboratory animals.

Trichosanthin, a protein purified from the extract of the root tuber of Trichosanthis Kirilowii, Maxim, given once only induced midterm abortion in the mice and rabbits. The effective I.P. dose for the induction of abortion in 10- or 11-day pregnant mouse was 50 micrograms. In the rabbit a dose and state of pregnancy-dependent response to Trichosanthin-induced abortion was encountered. A dose as low as 0.5 mg Trichosanthin in 22-day pregnant rabbit was adequate but 2.0 mg was needed in 17-day pregnant rabbit. Attempts to terminate pregnancy in the rat and hamster using Trichosanthin was not successful even with higher doses. When compared with prostaglandin-F2 alpha, an established abortifacient, Trichosanthin appeared to be more effective and associated with less side effects in the induction of abortion in the rabbit. Trichosanthin was ineffective to terminate early pregnancy in the 4 species studied.

Abortifacient Agents↗

Effects of 17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one (RMI 12,936) on pregnant rabbits.

A single subcutaneous injection of RMI 12,936 interrupted 8- and 15-day pregnancy in the rabbit. A dose dependent loss of embryos was observed. Higher doses of RMI 12,936 were needed to terminate pregnancy in 8-day pregnant (74% efficacy with 10 mg/kg) than in 15-day pregnant rabbits (100% efficacy with 8 mg/kg). Termination of pregnancy by RMI 12,936 was accompanied by a significant increase of progesterone (delta 4 p) in rabbits receiving 10 mg/kg RMI 12,936 on day 8 of pregnancy. On the other hand, treatment with 8 mg/kg RMI 12,936 on day 15 of pregnancy did not alter the delta 4 p levels, but induced a significant decrease in 20 alpha-dihydroprogesterone. In these two treatment groups, a consistent and highly significant increase of serum testosterone (T) was observed. The increase of T value possibly was due to a decrease in aromatizing ability of the follicles after RMI 12, 936 treatment and might have contributed towards the interruption of pregnancy. The failure of RMI 12,936-treated rabbits to ovulate even after hCG administration suggests that his compound might have lowered the sensitivity of the mature follicles to LH stimulation.

Androstenols↗

Termination of pregnancy in rabbit and mouse by Trichosanthin.

The effects of a single intraperitoneal injection of Trichosanthin in 6-, 10-, 17- or 22-day pregnant rabbit (2 mg/rabbit) or in 11-day pregnant mouse (50 micrograms/mouse) were studied. Trichosanthin induced abortion in 100% of the 17- or 22-day pregnant rabbits within 48-72 hours and decreased circulating progesterone (delta 4P)concentrations with 24 hrs. On the other hand, the same dose failed to terminate pregnancy in 6- or 10-day pregnant rabbits and caused no significant changes in circulating delta 4P levels. Exogenous delta 4P or prolactin + human chorionic gonadotropin given twice daily failed to reverse the Trichosanthin-induced termination of pregnancy. However, this resulted in a delay of fetal expulsion. It is concluded that Trichosanthin-induced termination of pregnancy is not solely a result of luteolysis but is likely to be due to its toxic effects on placenta, embryo or both. A dose of 50 microgram Trichosanthin given to 11-day pregnant mice resulted in a termination of pregnancy within 96 hours and also a significant decrease in delta 4P levels in 24 hrs. The ratio of delta 4P to 20 alpha-dihydroprogesterone was also decreased steadily after Trichosanthin administration.

20-alpha-Dihydroprogesterone↗

Temporary sterility induced by intrascrotal deposition of silastic-polyvinylpyrrolidone-prostaglandin F2alpha tubes in the rabbit: effect on fetal survival after regain of fertility.

In male rabbits of proven fertility, the intrascrotal deposition of two Silastic-polyvinylpyrrolidone tubes containing 3 mg of prostaglandin F2alpha (PGF2alpha)/tube induced within 2 to 4 weeks temporary sterility which lasted for 10 to 14 weeks. Associated with induced sterility were reduction in testicular weight, increase in abnormal spermatozoa (8% to 78% versus 0 to 3.7%), and reduction in sperm motility along the reproductive tract and in the semen for a period of 6 to 7 weeks. During the period of temporary sterility the weight of the epididymis, the sexual drive, and semen volume remained unaltered. Normal fertility was associated with an increase in testicular weight, reduction in the proportion of abnormal sperm, and improved sperm motility. In addition to an altered spermatogenesis, the integrity of mature spermatozoa seemed to be severely affected after PGF2alpha treatment. The reduced number of viable young sired by males that recovered from temporary sterility (pregnancy wastage 35%) as compared with sham-treated controls (pregnancy wastage 3%) suggests that a small percentage of spermatozoa might still be defective at the time of testing. A longer waiting period might be needed to ensure a completely normal reproductive process.

Animals↗

Variations in serum androgens, estrogens, progestins, gonadotropins and prolactin levels in male rats from prepubertal to advanced age.

The concentrations of blood serum steroids from 12 to 450 days old male rats were determined by radioimmunoassay. Testosterone (T) was low (270 pg to less than 1 ng/ml) until day 42; adult levels (3--4 ng/ml) were attained by day 62 and declined tradually with advanced age. 5 alpha-dihydrotestosterone (5 alpha-DHT) did not change markedly (90--160 pg/ml) from prepubertal to advanced age. Except for a small peak on day 22, androstenedione (delta 4 A) levels ranged between 400-500 pg/ml in the adult but declined in older males. Progesterone (delta 4 P) rose steadily to a mean of 5.46 ng/ml at 52 days of age and dropped thereafter. High levels of estrone (268 +/- 38 pg/ml) and estradiol-17 beta (2.76 +/- 0.28 ng/ml) in 12 days old males are in contrast to the low estrogens (20-35 pg/ml) in adult animals. Both T/5 alpha-DHT and total T/estrogen ratios were low before puberty, increased in adults and decreased towards old age. The interplay between gonadotropin and prolactin, which exhibited reciprocal changes in the regulation of steroid production by the gonads with age, are discussed.

Aging↗

Age dependent changes in the sperm population and fertility in the male rat.

The entire reproductive tract was devoid of spermatozoa during the first 42 days of life. The first appearance of spermatozoa was detected in the caput epididymidis of 45-day old rats and in the cauda epididymidis of 52-day or older rats. The number of spermatozoa in the reproductive tract increased with age. The sperm population reached its maximum in the caput epididymidis by day-72 and in the caud epididymidis by day-100. These high levels were maintained beyond 450 days of age. Fifty-two day old male rats failed to impregnate the female. Although male rats of 62-500 days were able to sire litters, the peak reproductive period was found to be between days 100-270, during which the number of young per litter ranged between 11-16. Towards advanced age the litter size dropped to 8. The lower fertility in the males of advanced age might be due to a lower proportion of fertile spermatozoa, a change in the physiology of epididymis or an altered sperm transport in the reproductive tract.

Aging↗

Effects of cadmium chloride on testicular steroidogenesis and fertility of male rats.

Effects of a single subcutaneous injection of 1 or 5 mg/rat of cadmium chloride (CdCl2) on circulating steroids and fertility were studied over a period of 120 days in fertile male rats. Androgens and fertility returned to normal 120 days after 1 mg CdCl2 but males treated with 5 mg showed none to poor restoration of some of these parameters. The in vitro release of testosterone (T), 5 alpha-dihydrotestosterone (5 alpha-DHT) and androstenedione (delta 4A) by the decapsulated tests from CdCl2 treated males was significantly reduced whereas progesterone (delta 4P) was accumulated in significantly higher amounts into the incubation medium. When testes from CdCl2 treated males were incubated in vitro with hCG, a dose and time dependent stimulation of steroidogenesis was evident. Since the testes regained the steroidogenic capacity but the males remained sterile 120 days after 5 mg CdCl2 treatment, it appeared that CdCl2 induced a permanent damage to the germinal components of the testes.

Androgens↗

Effects of prostaglandin-F2alpha on some reproductive parameters of fertile male rats.

Silastic-PVP-PGF2alpha tubes significantly reduced the sperm population in the epididymis and vas-deferens of male rats 14 days after their insertion into the scrotal sacs. A reduction in testis and epididymal weights was also evident. The reduction of sperm population was accompanied by a normal sexual drive and circulating testosterone level and partial sterility. The reduction in sperm population and induction of partial sterility was detected at least 7 days after the total release of prostaglandin F2alpha from the Silastic-PVP tubes. The results suggest that the changes in the reproductive parameters might be a consequence of endocrinological and functional disturbances induced by PGF2alpha and that PGs can be used to induce temporary sterility in the male.

Animals↗

Prostaglandin F2alpha induced termination of pregnancy and its reversal by prolactin or progesterone in rats.

Intrauterine insertion of a Silastic-PVP tube containing 400 microgram PGF2alpha terminated midterm pregnancy in 100 per cent of the animals. Progesterone (2 mg/day) or prolactin (PRL) reversed the abortifacient effect of PGF2alpha. A dose- and duration-related effect of the PRL on PGF2alpha induced termination of pregnancy was evident. The results suggest that PGF2alpha and PRL are antagonistic to each other and multiple doses of PRL are needed to neutralize the luteolytic action of PGF2alpha.

Abortifacient Agents↗

Circulating plasma levels of pregnenolone, progesterone, estrogen, luteinizing hormone, and follicle stimulating hormone in young and aged C57BL/6 mice during various stages of pregnancy.

Young (3-5 mo of age) and senescent (12-15 mo of age) multiparous C57BL/6 mice were mated with young males (3-6 mo of age) and the numbers of preimplantation embryos and implantation sites determined on days 1 (day of plug), 4, 9, and 16 of pregnancy. The numbers of viable embryos were significantly lower (p less than 0.02 to p less than 0.001) in senescent females compared with young females on all days except day 1 of pregnancy. Plasma samples tested by radioimmunoassay indicated circulating estradiol-17B was significantly lower (P less than 0.05) on day 1 and higher (p less than 0.05) on day 4 in older females, whereas FSH was higher on days 4, 9, and 16 (p less than 0.02 to p less than 0.001) in senescent females when compared with samples from young females. Levels of pregnenolone, progesterone, estrone, and LH were not significantly different at any stage of pregnancy in the two age groups. From the hormonal data it did not appear that degenerating corpora lutea were responsible for the declining litter size in this strain of aged mouse.

Aging↗

Periovulatory steroid concentrations in HCG-treated rabbits.

The level of pregnenolone increased within 1 h and remained high for 4 h after an intravenous injection of HCG in conscious rabbits. Peaks for progesterone, estrogens and dehydroepiandrosterone were recorded at 2 h, and that of 20alpha-dihydroprogesterone 6 h after HCG injection. At the time of ovulation the serum concentrations of all steroids had returned to their basal levels. It seems that HCG maintained a high production of pregnenolone and promoted the synthesis of different steroids.

20-alpha-Dihydroprogesterone↗

Effects of hCG on serum levels of testosterone, dihydrotestosterone and androstenedione in male mice.

The concentrations of testosterone (T), 5alpha-dihydrotestosterone (5alpha-DHT) and delta4-androstenedione (delta4 A) in the circulating blood were increased by a single subcutaneous injection of 10 IU of hCG in the mouse. The response of androgen synthesis to hCG stimulation was rapid and persisted over a period of 96 h. The increased supply of T to the peripheral organ(s) under the stimulation of hCG might contribute to an increase in circulating 5alpha-DHT. However, the changes in T/5alpha-DHT ratio implies that the stimulation of T and 5alpha-DHT production by hCG were not of the same degree.

Androstenedione↗