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Biomedical subjects

I F Lau

Publications and source records attributed to I F Lau.

At least 19 recordsLinked to original sources
PubMed1982

The concentration of progesterone, 20 alpha-dihydroprogesterone, testosterone, oestrone and oestradiol-17 beta in serum, amniotic fluid and placental tissue of pregnant rabbits.

The concentrations of progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP), testosterone (T), oestrone (E1) and oestradiol-17 beta (E2 beta) in peripheral blood serum (PBS), amniotic fluid (AF) and placental tissue of rabbits during gestation were determined by radioimmunoassay. The placenta of the 10-day pregnant rabbit was fragile and composed mainly of maternal tissue. By the 12th day of pregnancy it was separable into maternal and foetal placentae. The mean concentration of delta 4P in PBS rose from 200 pg/ml (day 1 pregnancy) to 17--21 ng/ml (days 10--15) and decreased gradually to 1 ng/ml a few hours before parturition. The 20 alpha-DHP in PBS also showed an increase from 1.5 ng/mg (day 1) to 12 ng/ml (day 6) but fluctuated thereafter. The concentration of 20 alpha-DHP in the PBS tended to be lower than that of delta 4 P during pregnancy until the regression of the corpus luteum. An interesting observation was an increase of T on days 6--8 of pregnancy, the time when implantation occurs. The concentrations of E1 and E2 beta in PBS remained very low throughout pregnancy. delta 4P and 20 alpha-DHP in AF ranged between 25 pg to 1 ng/ml and in no case during the course of pregnancy were the levels of T, E1 and E2 beta in AF higher than in PBS. Where the maternal placental delta 4P content remained between 1--2 ng/placenta, the foetal placenta delta 4P rose to a level of 15 ng/placenta by day 31 of pregnancy. A similar trend was recorded for 20 alpha-DHP content. It is concluded that although a parallelism between PBS and myometrial steroid concentration was observed, no relationship could be drawn between the concentrations of steroid in PBS and those of the placental tissue and AF.

20-alpha-Dihydroprogesterone↗
PubMed1982

The pituitary-ovarian complex in the aged anoestrous golden hamster.

Plasma and pituitary hormones of young (3--5 months of age) dioestrous hamsters with normal cycles and aged (13--17 months of age) anoestrous hamsters were compared. The anoestrous hamsters exhibited lower plasma values of progesterone (P less than 0.001), oestradiol-17 beta (P less than 0.005) and prolactin (P less than 0.001) and higher levels of plasma gonadotrophins (P less than 0.001) than did the dioestrous animals. Pituitary concentrations of LH were higher (P less than 0.005) in anoestrous hamsters, but pituitary FSH and prolactin values did not differ. In another series of experiments three groups of hamsters (3--5- and 13--17-month-old with normal cycles and 13--17-month-old in anoestrus) were ovariectomized. Blood samples were taken by cardiac puncture every 3--4 weeks after receiving s.c. injections of oestradiol-17 beta (1 or 10 micrograms/100 g body wt) for 2 or 9 consecutive days. The markedly lower levels of gonadotrophins in aged anoestrous hamsters indicated that the hypothalamic-hypophysial complex was incapable of responding to the same degree as it did in young and aged cyclic animals. Prolactin values were similarly depressed in all 3 groups. Oestradiol-17 beta treatment caused reduced gonadotrophin and increasing prolactin concentrations in all 3 groups. These results indicate that the ovaries of the senescent anoestrous hamster produce less steroids and suggest that age-related changes in the hypothalamic-hypophysial complex are largely responsible for the cessation of regular oestrous cycles.

Aging↗
PubMed1981

Gossypol: its toxicological and endocrinological effects in male rabbits.

The effects of different doses of orally administered polyphenolic compound 'Gossypol' on semen quality, circulating testosterone (T) and fertility of Dutch-belted male rabbits were studied. Bucks fed daily with 80, 40, 20 mg/kg day gossypol died within 8-17, 23-35 or 35-84 days, respectively, after initiation of treatment. Following gossypol treatment at 80, 40 or 20 mg/kg/day, animals lost appetite and body weight, developed hind limb paralysis, breathing difficulties and collapsed while sitting in their cages. At autopsy, the liver and lungs were found congested while the stomach and intestines contained gases. On the other hand, rabbits fed daily with 10 mg/kg/day gossypol exhibited a survival time ranging from 77 to 250 days. Despite the severe side effects resulting in eventual deaths, weekly semen samples from all treated animals did not show any apparent change in sperm motility, morphology or population. Likewise, gossypol-treated males mated to estrous does exhibited a fertility comparable to vehicle-treated controls. Gossypol fed at a dose of 10 mg/kg/day for up to 35 weeks failed to induce sterility. Male rabbits, fed with either 20 or 10 mg/kg/day gossypol, that survived for longer periods of time had substantially reduced T levels by 12-20 weeks depending upon the dose but were fertile at all times. When the in vitro release of T from the rat testes mince in the presence of hCG and gossypol was evaluated, an inhibiton of T release was recorded. It is concluded that although gossypol has been shown to be an effective antifertility agent in several mammalian species, it failed to exhibit such an effect in Dutch-belted rabbits, although serum T levels were reduced. In addition, gossypol exhibited a wide spectrum of toxicity. The in vitro study demonstrated that high concentration of gossypol can directly inhibit the T synthesis in the testis.

Animals↗
PubMed1981

Effects of Colprone on in vitro release of androgens from the reproductive organs of the male rat.

Effects of medrogestone (6,17 alpha-dimethyl-4-,6-pregnadiene-3, 20-dione; Colprone) on the release of testosterone (T) and 5 alpha-dehydrotestosterone (5 alpha-DHT) in the reproductive organs of the male rat were tested in vitro. The minced testes released twice as much T into the medium when incubated in the presence of 50 mIU/ml of hCG. The release of T was inhibited significantly when 10 or 50 micrometers Colprone was added to the incubation medium. More 5 alpha-DHT was released into the medium from the testes mince in the presence of hCG, while the addition of 10 or 50 micrometers of Colprone inhibited 5 alpha-DHT release as compared to hCG controls. On the other hand, hCG failed to stimulate the release of T and 5 alpha-DHT from the minced caput and cauda epididymis and ventral prostate. The addition of Colprone (10--50 micrometers/ml) to the medium containing caput epididymis or ventral prostate resulted in a significant inhibition of T and 5 alpha-DHT. However, no significant change in the rate of T or 5 alpha-DHT release was recorded in medium containing cauda epididymis. In spite of its anti-androgenic effects reported by several investigators, Colprone in the present study has shown differential effects on T and 5 alpha-DHT release from different reproductive tissues of the male rat.

Animals↗
PubMed1981

Effects of 17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one on early pregnancy in the rat.

A single sc injection of 1 mg 17-beta-hydroxy-7 alpha-methylandrost-5-en-3-one (RMI-12,936) given a few hours after mating interrupted pregnancy in all the treated rats. Circulating progesterone (delta 4P) levels were higher in RMI-12,936 treated females than in controls on the corresponding days during the course of termination of pregnancy. Higher levels of delta 4P were recorded on day-4 (P less than 0.01) and day-6 (P less than 0.05) of pregnancy. In addition to the changes in serum delta 4P, an acceleration of egg transport was encountered. The eggs were prematurely expelled from the uterus within 48 h of the treatment. Although the oestrous cycle of the RMI-12,935 treated females was disturbed, they were found sexually receptive. Successful matings resulting in normal gestation and morphologically normal foetuses were recorded 20-26 days after RMI-12,936 induced pregnancy termination. These results suggest that in addition to its mid-pregnancy terminating effect, RMI-12,936 is capable of interrupting early pregnancy when given soon after mating in the rat. The safety and efficacy of this compound as a post-coital contraceptive deserves further investigation.

Abortifacient Agents↗
PubMed1980

Further studies on the trichosanthin-induced termination of pregnancy.

Trichosanthin (TCS), a protein from the root extract of Trichosanthis kirilowii, terminated pregnancy when injected once in 15-day pregnant rabbits (2 mg/doe) but failed to interrupt pregnancy in 12-day pregnant rabbits even at higher doses. In vitro release of progesterone (delta 4P) from the maternal or fetal placental tissue into the incubation medium was not affected by TCS. When the distribution of 125I-TCS was traced in 12-day pregnant mice, persistently higher concentration of 125I-radioactivity was detected in the kidney. By contrast, in other organs, including the reproductive organs, blood serum and amniotic fluid 125I-radioactivity declined between 12-48 h after treatment. The low 125I-radioactivity in both the reproductive organs and amniotic fluid suggests a possible barrier between the embryo and maternal blood. It is suggested that TCS might be acting directly on the placental unit, causing fetal death and dislodging of the placenta. Administration of TCS to PD-19 mice or PD-28 rabbits resulted in premature delivery. This effect of TCS in pregnant mice was comparable to the administration of PGF2 alpha.

Abortion, Spontaneous↗
PubMed1980

Temporal relationship between progestin and luteinizing hormone concentrations in pseudopregnant rats treated with prostaglandin-F2 alpha.

The temporal changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and luteinizing hormone (LH) concentrations in pseudopregnant (PSP) rats after treatment with a single subcutaneous Silastic-PVP tube containing 600 micrograms PGF2 alpha were correlated. Progesterone levels fell and LH levels rose significantly 2h after initiation of treatment, while 20 alpha-DHP levels were found to increase significantly 12h after treatment. Since the changes in delta 4P and LH concentrations occurred concurrently, it seems that the increase in LH levels could have been due to a direct effect of PGF2 alpha on the ovary causing a reduction in delta 4P and thus a negative feedback effect on LH release. Alternatively, PGF2 alpha might exert a direct effect on LH secretion at the hypothalamic-pituitary level.

20-alpha-Dihydroprogesterone↗
PubMed1980

Effects of prostaglandin F2 alpha and an antiprogestational steroid, RMI 12,936, on rat pregnancy.

The abortifacient efficacy of RMI 12,936 (17 beta-hydroxy-7 alpha-methyl androst-5-en-3-one), a synthetic steroid, alone or in combination with prostaglandin-f2 alpha (PGF2 alpha), was studied in the rat. Administration on day-8 of pregnancy (PD-8) of 0.25 mg RMI 12,936/rat neither altered the progesterone (delta 4P) levels, the relative ovarian weight (ROW) nor terminated pregnancy. Doses of 2.0, 1.0 or 0.5 mg RMI 12,936/rat, when given on PD-8, terminated pregnancy in 100% of the animals. Highly significant increases in ROW and serum alpha 4P level were recorded on PD-14. However, delta 4P/20 alpha-dihydroprogesterone ratio remained unaltered. These results suggest that RMI 12,936 increased luteal activity which contributed to the enhanced serum delta 4P levels and ROW. Bilateral insertion of Silastic-PVP tubes containing 75 micrograms PGF2 alpha/tube into each uterine horn on PD-10 did not disturb pregnancy, whereas similar tubes given on PD-10 to rats treated with 1.0 mg RMI 12,936 on PD-8 expelled the embryos and placental tissue on PD-11. This phenomenon was attributed to a decreased serum delta 4P caused by PGF2 alpha, allowing the expulsion of uterine contents. A time lapse of 17--35 days was needed for the rats to regain fertility in terms of normal gestation period and offsprings. Although expulsion of conceptus was facilitated by PGF2 alpha in the RMI 12,936 treated rats, PGF2 alpha treatment did not alter the time lapse between RMI 12,936 treatment and subsequent conception. It is concluded that RMI 12,936 is feto-toxic; it possesses high contraceptive activity and its abortifacient efficacy can be improved by PGF2 alpha.

Abortion, Induced↗
PubMed1980

Effects of prostaglandin-F2 alpha and a plant protein "Trichosanthin", on 10-day pregnant rabbits.

The effect of Trichosanthin (TCS), a protein obtained from the roots of Trichosanthis kirilowii, alone or in combination with prostaglandin-F2 alpha (PGF2 alpha; Tromethamine salt) on the termination of pregnancy in rabbits was investigated. Intraperitoneal injection of 1 or 2 mg TCS/10-day pregnant rabbits neither altered the serum progesterone (delta 4P) level nor interrupted pregnancy. Doses of 0.5 or 0.25 mg PGF2 alpha incorporated in a Silastic-PVP tube and inserted intravaginally, terminated pregnancy within 72 h of treatment in 75 and 16% of the treated does, respectively. By contrast, does treated on day-10 of pregnancy with a combination of a non-effective dose of TCS (1 mg) and a sub-effective dose of PGF2 alpha (0.25 mg) terminated pregnancy in all the treated animals as no live embryos were found within 3 days of treatment. Pregnancy interruption was associated with a significant reduction of serum delta 4P and delta 4P/20 alpha-dihydroprogesterone (20 alpha-DHP) ratio. The present study indicates that TCS and PGF2 alpha act synergistically, rendering the termination of 10-day pregnancy possible in the rabbit. It was also noted that pregnancy cannot be maintained when the serum delta 4 P level drops below 4 ng/ml and delta 4P/20 alpha-DHP falls lower than 0.6 in the 10-day pregnant rabbit.

Abortifacient Agents↗
PubMed1979

Effects of RMI 12,936 on some reproductive processes in the female golden hamster.

A single subcutaneous injection of 2 mg RMI 12,936 (17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one) given a day after estrus disrupted estrous cycle for over 30 days and inhibited ovulation in 100 percent of treated Golden hamsters. Administration of RMI 12,936 (2 mg) on Day 6 of pregnancy caused termination of pregnancy within 4 days of treatment. In association with the termination of pregnancy was a significant reduction in the concentrations of progesterone and estradiol-17 beta together with an elevated testosterone level. After termination of pregnancy by RMI 12,936, the hamsters remained sexually receptive for 4 weeks but failed to conceive. It is concluded that RMI 12,936 causes termination of pregnancy due to an induction of functional luteolysis.

Abortion, Spontaneous↗
PubMed1979

RMI 12,936 and pseudopregnancy in rats.

RMI 12,936, when injected subcutaneously at a dose of 2 mg, either on Day 6 of psuedopregnancy (PSP-6) or on PSP-6,7 and 8, shortened the duration of PSP from 12.3 +/- 0.3 (control) to 8.3 +/- 0.1 or 8.7 +/- 0.2 days, respectively. During PSP, plasma progesterone (delta 4P) levels in the peripheral plasma showed a trend of decrease by PSP-9 (52.0 +/- 4.6 on PSP-8 to 42.3 +/- 3.1 ng/ml on PSP-9). Administration of RMI 12,936 on PSP-6 resulted in a significant decrease in delta 4P and pregnenolone (delta 5P) within 24 hr after treatment but caused no apparent changes in 20 alpha-dihydroprogesterone (20 alpha-DHP) levels. However, a significant decrease of delta 4P/20 alpha DHP ratio was encountered 24 hr after RMI 12,936 treatment. The persistent occurrence of proestrous smear after PSP termination, but absence of estrous vaginal cytology, might be attributed to the slight estrogenicity of RMI 12,936. After the premature termination of pseudopregnancy induced by RMI 12,936, the female rats were sexually receptive for at least 3 weeks but failed to conceive, suggesting that this compound has a prolonged contraceptive effect.

Androstenols↗
PubMed1979

Termination of pregnancy in the rat by RMI 12,936.

Administration of a steroid RMI 12,936 (2 MG) ON DAY 8 OF PREGNANCY RESULted in an interruption of gestation within 5 days. No significant changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and pregnenolone (delta 5P) were recorded during the course of termination of pregnancy by RMI 12,936. However, a significant rise in serum delta 4P and hypertropic corpora lutea were evident on day 13 of pregnancy when all treated females showed dead conceptus. The placental tissue was still present at the time of pregnancy termination. On the other hand, serum LH levels was significantly suppressed 24 hr after the treatment and maintained at a very low level. The reduction of LH might be due to a lowered hypophyseal sensitivity towards LH-RH. The occurrence of in utero dead fetus without interference of delta 4P production suggests that in the rat RMI 12,936-induced termination of pregnancy is due to its embryotoxic rather than luteolytic effect. Although the treated females did not return to normal estrous cycles for a period of 2 weeks after pregnancy termination, they were sexually receptive. Successful mating resulted in normal pregnancy which occurred 30-35 days after RMI 12,936 treatment.

Abortifacient Agents↗
PubMed1979

Termination of pseudopregnancy in rats by silastic-PVP-PGF2 alpha tube.

The efficacy of a one-end or both-end open Silastic-polyvinyl-pyrrolidone (Silastic-PVP) tube containing 600 microgram prostaglandin-F2 alpha (PGF2 alpha) and placed subcutaneously on day-6 of pseudopregnancy (PSP) in the induction of premature termination of PSP was compared. A both-end open Silastic-PVP-PGF2 alpha tube was more efficacious in inducing an early termination of PSP with a mean duration of 7.8 days. By contrast, PSP females receiving a one-end open Silastic-PVP-PGF2 alpha tube showed a mean duration of PSP of 9.9 days. The shortened duration of PSP in both these treatment groups was significantly different from the control value of 13.1 days. The significant drop in progesterone (delta 4P) but rise in 20 alpha-dihydroprogesterone (20 alpha-DHP) occurred 24 hr after treatment in PSP rats treated with both-end open Silastic-PVP-PGF2 alpha tube, whereas similar changes in delta 4P and 20 alpha-DHP took place 48-72 hr after the deposition of a one-end open Silastic-PVP PGF2 alpha tube. It is concluded than an initial larger amount of circulating PGF2 alpha is needed to induce an early premature termination of PSP. The exposure of corpus luteum to a more sustained but lower level of PGF2 alpha leads to a slower response.

20-alpha-Dihydroprogesterone↗
PubMed1979

Inhibition of ovulation and fertilization by indomethacin and effect of prostaglandin-F2 alpha on early pregnancy in the rabbit.

Ovulation induced by HCG in rabbits was blocked by a single subcutaneous injection of 6 mg/kg indomethacin given 6 h after the insemination and HCG treatment. In addition, a time-dependent inhibition in the fertilization rate after indomethacin treatment was also recorded. This suggests that indomethacin, when given at a critical time and at an appropriate dose level, not only blocks ovulation but also interferes with fertilization. Treatment with graded amounts of prostaglandin-F2 alpha incorporated in a Silastic-polyvinylpyrrolidone-gel (PVP) had marginal to no effect after intravaginal placement on 4- or 6-day pregnancy. However, 5 mg PGF 2 alpha/ Silastic-PVP tube when placed intravaginally on Day-7 of pregnancy resulted in termination of pregnancy in 66% of the treated does. This implies that young corpora lutea are resistant of PGF2 alpha treatment and that pregnancy at the time of ovo-implantation can be terminated by PGF2 alpha incorporated in a Silastic-PVP tube.

Animals↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗