M.C. Chang

Pregnancy blockade by indomethacin, an inhibitor of prostaglandin synthesis: Its reversal by prostaglandins and progesterone in mice

Abstract Results in the present study clearly indicate that subcutaneous injections of indomethacin (150 μg/day) to the pregnant mice on days 1,2,3 and 4 of pregnancy terminate pregnancy in 100 percent of the animals. A single injection of 225 μg/day/mouse on day 2 of pregnancy results in 100 percent inhibition of pregnancy. Since this dose of indomethacin was not as effective when given either on day 1, 3 or 4 of pregnancy, it is likely that indomethacin acts through a tubal disturbances by suppressing prostaglandins for the retention of the ova. Progesterone (0.75 mg/day) and prostaglandins E 2 and F 2α (50 μg/injection) reverse the anti-implantation effect of indomethacin. Other possibilities are that indomethacin exerts its antifertility effect i) by delaying nidation, ii) by an indirect or direct effect on the developing embryos, iii) by causing a hormonal imbalance which results in either progesterone deficiency or by suppressing the circulating level of luteinizing hormone.

The inhibition of the conversion of testosterone into 5α-dihydrotestosterone in the reproductive organs of the male rat

The inhibition of testosterone 5alpha-reductase activity by 3-oxo-4-androstene-17beta-carboxylic acid in the male reproductive organs of the rat was demonstrated in vitro. The medium for incubation of caput epididymis showed the highest concentration of 5alpha-dihydrotestosterone (5alpha-DHT) whereas the highest concentration of testosterone (T) was recorded in medium for incubation of decapsulated testis after two hours of incubation. The 3-oxo-4-androstene-17beta-carboxylic acid (1.58 X 10(-5)M) inhibited the conversion of T to 5alpha-DHT in all the organs tested (testis, caput and cauda epididymis and ventral prostate) under identical incubation conditions.

Temporal changes in circulating steroids during prostaglandin F2α induced abortion in the rat and rabbit

The serum levels of progesterone (delta4P), 20alpha-dihydroxyprogesterone (20alpha-DHP), pregnenolone (delta5P) and estrogens at different time intervals during Silastic-PVP-PGF2alpha tube induced midterm abortion were measured by radioimmunoassay in the rat and rabbit. The concentrations of delta4P and delta5P were significantly reduced but that of 20alpha-DHP was increased significantly as early as 20 hours after PGF2alpha treatment. Estrogen levels showed slight reduction in the rat but remained unchanged in the rabbit. The ratio of delta4P/20alpha-DHP recorded were 2.15 and 16.86 (pretreatment) and dropped to 0.08 and 0.37 (60 hours after insertion of Silastic-PVP-PGF2alpha tube) in the rat and rabbit, respectively. These findings suggest that the suppression of circulating delta4P by PGF2alpha might be the result of a reduced precursor (delta5P) pool size as well as changes in the enzymic systems responsible for the formation and conversion of delta4P. It is still to be determined if changes in estrogen levels in the rat have any bearing on abortion induced by PGF2alpha.

Determination of Seven Unconjugated Steroids in the Blood and Seminal Plasma of the Fertile Male Rabbit

Seven unconjugated steroids were measured in the blood and seminal plasmas of fertile male rabbits by radioimmunoassay. The blood plasma testosterone concentration was 4--5 times that of the seminal plasma. Dehydroepiandrosterone, estrone and 17beta-estradiol were found in measurable amounts in the blood plasma; however, these steroid levels were slightly lower in seminal plasma. Androstenedione and 5alpha-dihydrotestosterone were present in equal quantities in both the seminal and blood plasmas. By contrast, seminal plasma pregnenolone level was about twice that of the blood plasma. The determination of seminal plasma steroids may lend itself as a complementary assessment to blood steroid determinations for the evaluation of the normal function of various reproductive organs.

Effect of prostaglandin F2α on ovulation and fertilization in rabbit

Abstract The effect of prostaglandin F 2α on ovulation and fertilization was studied in rabbits. The number of ovulation was not affected by subcutaneous injection of PGF 2α but the recovery of ova was significantly decreased when PGF 2α was given either at 12 or 16 h after HCG injection and autopsied 24 h latter. The results suggest that exogenous PGF 2α accelerates ovum transport and expels the eggs prematurely from the female tract and does not impair ovulation or the fertilization processes when given to rabbit at 1 mg/kg B.W.

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.

Prostaglandin E2: Midterm abortion in rats using Silastic-PVP tubes

Abstract The results of the present study establish that 1.5 mg PGE2 (lyophilized sodium salt) incorporated in one cm long open-ended Silastic-polyvinylpyrrolidone (PVP) tube when inserted into 10 day pregnant rats induced abortion within 70–72 hours in all the treated rats. A combined treatment of PGE2 and 17β-estradiol failed to increase the abortion inducing effect of a Silastic-PVP-PGE2 tube. It is observed that PGE2 is about 4 times less potent than PGF2α in inducing midterm abortion in rats. It is suggested that either PGE2 exerts luteolytic effect after being converted in vivo to PGF2α, although how it occurs is not clear; or PGE2 causes expulsion of the fetuses by its uterine stimulating property. 17β- estradiol increases the uterine synthesis of PGF2α as described earlier but seems not affecting the production of PGE2 by the uterus. The release rate of 3H-PGE2 from Silastic-PVP tube in vitro and in vivo is also described.

Effects of prostaglandin-f2α 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.

Induction of temporary sterility in female hamsters by an intraperitoneal Silastic-PVP-PGF2α tube

In the female hamster, temporary sterility for a period of 10 or 15 days was induced by an intraperitoneal Silastic-PVP-tube containing 3.5 or 1.0 mg of PGF2alpha, respectively. All Silastic-PVP-PGF2alpha tube hearing animals regained fertility and delivered normal litters at various times after the placement of the tube. The release rate of 3-H-PGF2alpha from the Silastic-PVP tube was described and their potential use as a drug delivery system discussed.

Effects of prostaglandin F2α (PGF2α) on the length of pseudopregnancy in normal and IUD bearing hamsters

Abstract Prostaglandin F 2α (PGF 2α ) at 14, 30 or 50 μg/hamster/day from Days 3–5 of pseudopregnancy (PSP) shortens PSP from a mean length of 9.1 to 5.6–7.9 days, depending on the dose of PGF 2α administered. Bilateral intrauterine device (BIUD) bearing hamsters exhibit a mean length of PSP of 9.2 days, which is comparable to that in normal saline controls. Combination of PGF 2α (14 μg/day on Days 3–5 of PSP) and BIUD also resulted in shortening of PSP although the mean length of PSP resulted from the combined treatment was not significantly different from those PSP animals treated with 14 μg/day of PGF 2α alone. It is concluded that the antifertility effect of intrauterine device possibly is attributed to a small and continuous release of PGF which interferes with the normal implantation processes but does not curtail PSP.