S.K. Saksena

Effects of Gossypol on the fertility of male rats, hamsters and rabbits.

Oral administration of Gossypol acetic acid induced sterility in male hamsters and rats when given at a dose level of 5 or 10 mg/kg daily for 12 weeks. This was shown by the appearance of dead and abnormal sperm in the male tract and the failure of pregnancy or decrease in implantation sites in the females mated to the Gossypol-treated males. Similar treatment of male rabbits at dose levels varying from 1.25 to 10 mg/kg and given for 5 to 14 weeks did not affect the average number of sperm per ejaculate, although the motility of sperm was poor during treatment in some bucks. The pregnancy rates and the proportion of implantation sites were also not affected by insemination of female rabbits with sperm from males during treatment with Gossypol.

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.

Prostaglandins E2 and F2α decrease plasma testosterone levels in male rats

Abstract Prostaglandins PGE 2 and PGF 2α depressed significantly the plasma testosterone levels when given subcutaneously to mature male rats at a dose of 500 μgm/rat/injection, b.i.d. for three days in normal saline or 250 μgm/rat/injection, b.i.d., for four days in sesame oil. Comparable treatments of PGE 1 and PGF 1α (250 μgm) in sesame oil or lower doses of PGE 2 and PGF 2α in saline (25 μgm) failed to depress significantly the plasma testosterone concentration. In addition, the 500 μgm treatment of PGE 2 and PGF 2α lowered plasma LH concentration although this decrease was significant only with PGF 2α . Constriction of testicular vasculature and/or a decrease in plasma LH levels may account for, or contribute to this action of the prostaglandins.

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.

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.

Effect of IUDs, Prostaglandins and Indomethacin on Decidual Cell Reaction in the Rat

Abstract The presence of an intrauterine device in the pseudopregnant (PSP) rat suppressed decidual cell reaction (DCR). Treatment with PGF 2α or PGE 2 also suppressed DCR, but had no effect on IUD horn. Treatment with PGF 2α from days 1–4 before trauma in ovariectomized rats treated with estradiol and progesterone did not have a significant effect on DCR. However, when PGF 2α was given for 4 days after trauma there was significant inhibition of DCR indicating a direct endometrial effect of PGF 2α . Inhibition of DCR was also recorded when indomethacin was administered to intact PSP or to ovariectomized rats maintained on estradiol and progesterone. This indicated that prostaglandins probably are necessary for normal DCR.

Effect of exogenous estradiol and progesterone on the uterine tissue levels of prostaglandin F2α(PGF2α) in ovariectomized mice

Abstract Mice ovariectomized for 14 days were treated for 6 days with estradiol and/or progesterone. Both the steroids were effective in increasing the levels of PGF 2α in the uterine tissue, but the treatment with progesterone for 3 days followed by 3 days of estrogen resulted in a highly significant production of PGF 2α . It is concluded that for the production of PGF 2α both estrogen and progesterone are necessary and that the pretreatment with progesterone followed by estrogen results in the maximum production of PGF 2α .

Levels of F prostaglandin (PGF) in uterine tissue during the estrous cycle of hamster: effects of estradiol and progesterone.

Abstract The uterine content and concentration of PGF varied throughout the estrous cycle of the hamster. The content was highest between 2400 hr of day 4 and 0030 hr of day 1, and lowest between 1045 to 1145 hr of day 1. The concentration was highest between 1045 to 1145 hr of day 2 and between 2400 hr of day 4 and 0030 hr of day 1, and lowest between 1045 to 1145 hr of day 1. The changes did not correlate well with the times of maximum and minimum secretion of PGF in uterine vein blood of the hamster reported by Shaikh and Saksena (19).

Prostaglandins E and F in uterine venous plasma in relation to peripheral plasma levels of progesterone and 20α-hydroxyprogesterone in the rat throughout pregnancy and parturition

Prostaglandins E and F in uterine venous plasma and progesterone (P) and 20alpha-hydroxyprogesterone (20alpha-OH-P) in peripheral plasma were measured by radioimmunoassays throughout pregnancy and parturition in the rat. E Prostaglandins are low (approx. 2 ng/ml) and maintain a more or less constant level throughout most of the pregnancy except just before parturition when they rise to 3.8 ng/ml on day 20. F Prostaglandin levels are always higher than E prostaglandins and show distinct peaks around day 5 (5 ng/ml), day 11 (7 ng/ml), and before parturition (8.4 ng/ml). Progesterone levels are higher than 20alpha-OH-P levels throughout most of the pregnancy (day 6-20); however, during early pregnancy (day 1-5) and before parturition more 20alpha-OH-P than P is present in peripheral blood. The possible role of uterine venous prostaglandin levels in altering the 20alpha-OH-P/P ratio during pregnancy and parturition is discussed.

Prostaglandin mediated action of IUD's (II) F-prostaglandins (PGF) in the uterine horn of pregnant rats and hamsters with intrauterine devices

Abstract The present investigation clearly shows that the presence of an IUD is associated with uterine hypertrophy and an increased production of F-prostaglandins. In the hamster, a bilateral IUD produced a significant increase in peripheral plasma PGF, presumably of uterine origin and an increased uterine PGF content at 2230 – 2300 h of day 4 of pregnancy. Earlier sampling (1530 – 1600 h) on the same day of pregnancy did not reveal any significant difference. In the rat, uterine PGF content and concentration, as well as PGF levels in uterine venous plasma were all increased in the IUD bearing horn from day 4 pregnant animals at 1530 – 1630 h in comparison to the contralateral control horn.