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Biomedical subjects

C H Spilman

Publications and source records attributed to C H Spilman.

At least 37 records · Page 2Linked to original sources
PubMed1980

Steroid binding specificity of the hamster uterine progesterone receptor.

The relative binding affinities (RBA) of 51 steroids were determined for the uterine progesterone receptor of the proestrous hamster. The receptor demonstrated a high specificity for progesterone; most structural modifications to the progesterone molecule resulted in a substantial reduction in binding affinity. Only six steroids had relative binding affinities similar to progesterone (RBA=100): 17 alpha-ethinyl-17 beta-methoxy-4-androsten-3-one (RBA=85); 6 alpha-fluoro-4-pregnene-3,20-dione (RBA=94); 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (RBA=96); 19-nor-4-pregnene-3,20-dione (RBA=110); 21-fluoro-4-pregnene-3,20-dione (RBA=119); and 17 alpha-ethinyl-17 beta-methoxy-4-estren-3-one (RBA=123).

Animals↗
PubMed1980

Effects of prostaglandins on peripheral progesterone and uterine diamine oxidase in the pregnant hamster.

Serum progesterone and uterine levels of diamine oxidase (DAO) activity were determined during pregnancy in hamsters. Progesterone was elevated on Day 1 of pregnancy, had a transient peak on Day 5, remained relatively constant on Days 6-10, and then increased on Days 13 and 14. Uterine DAO activity could not be detected until Day 7 of pregnancy approximately 1 1/2 days after the initiation implantation. DAO activity was associated with placental tissue, and more than 90% of the activity was localized in the maternal placenta. The temporal relationship between changes in serum concentrations of progesterone and uterine levels of DAO activity following PG administration also was studied. Serum progesterone was significantly depressed by 6 hr after treatment with PGs on Day 7 of pregnancy. However, uterine levels of DAO activity at 6 hr in the treated animals were not different from those in control animals. In contrast, both the serum progesterone concentrations and uterine levels of DAO activity were significantly lower at 24 hr after PG treatment. The effects of PG treatment on uterine DAO activity were completely blocked by concomitant administration of progesterone. However, concomitant administration of Provera only blocked the effect of one PG analog that was tested (9-deoxo-9-methylene-16,16-dimethyl-PGE2). The data indicate that changes in uterine DAO activity following treatment with the PGs used here are primarily a consequence of a decrease in peripheral progesterone (i.e. a luteolytic effect of the PG).

Amine Oxidase (Copper-Containing)↗
PubMed1978

Effect of 15(S)-15-methyl prostaglandin F2alpha on human oviductal motility and ovum transport.

The effects of an intravenous infusion of 15(S)-15-methyl prostaglandin F2alpha (PGF2alpha) on oviductal motility and ovum transport were studied in women who were scheduled for elective tubal sterilization. Infusion rates of 0.38 microgram/kg/hour or higher caused an increase in oviductal motility in all patients. Lower infusion rates did not always cause a stimulation of motility. Low infusion rates generally caused an increase in the amplitude of contractions without any effect on basal oviductal tone. The higher infusion rates usually caused a large increase in basal tone as well as an increase in the amplitude of contractions. Ova were recovered from the oviducts of five patients who had received an intravenous infusion of 15(S)-15methyl PGF2alpha. The ova were recovered from the ampulla in three patients, from the ampullary-isthmic junction in one patient, and from the isthmus in one patient. Since one would expect to recover ova from the oviducts at similar times under normal circumstances, there was no evidence that this prostaglandin treatment caused an acceleration of ovum transport. These data support the conclusion that a PGF analog which stimulates oviductal motility does not necessarily also accelerate ovum transport in women.

Fallopian Tubes↗
PubMed1977

Effects of 19-hydroxy-prostaglandins on oviductal and uterine motility.

The effects of 19-hydroxyprostaglandins (19-OH-PGs) were tested in vivo on the rabbit oviduct and uterus and on the rhesus monkey (Macaca mulatta) uterus. The 19-OH-PGEs suppressed spontaneous oviductal and uterine activity in the rabbit. The qualitative effect on the rabbit oviduct of 19-OH-PGEs was similar to that of PGE2. However, the typical response of the rabbit uterus to PGE2 was an increase in muscle activity. With regard to the rabbit oviduct, 19(R)-OH-PGE2 was as potent as PGE2, but 19(S)-OH-PGE2 was approximately 1/2 as potent as PGE2. Based on the dose of 19-OH-PGEs usually required to cause a minimal suppression and the dose of PGE2 required to cause a minimal stimulation of rabbit uterine activity, 19(R)-OH-PGE2 was twice as potent as PGE2 while 19(S)-OH-PGE2 was 1/2 as potent as PGE2. Stimulatory effects on the rabbit oviduct and uterus were observed following administration of 19-OH-PGFs and PGF2alpha. The potency on the rabbit oviduct of 19(S)-OH-PGF2alpha was about 1/5 to 1/10 that of PGF2alpha; the potency of 19(R)-OH-PGF2alpha was about 1/10 to 1/20 that of PGF2alpha. Both 19-OH-PGFs were approximately 1/5 to 1/10 as potent as PGF2alpha on the rabbit uterus. At the doses tested 19-OH-PGFs were inactive on the monkey uterus. Thus, these compounds are at least 1/5 as active as PGF2alpha. In contrast, 19(R)-OH-PGE2 had approximately the same potency as PGE2 in stimulating monkey uterine activity; but 19(S)-OH-PGE2 was approximately 1/3 as potent as PGE2.

Animals↗
PubMed1977

Effects of PGF2alpha and PGF2alpha, 1-15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey.

The effects of prostaglandin (PG)F2alpha and PGF2alpha, 1-15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF2alpha, 1-15 lactone were significantly (P less than 0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P less than 0.008) lower by the second day after the initial treatment with either PGF2alpha or PGF2alpha, 1-15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P less than 0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF2alpha, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF2alpha, 1-15 lactone. These data indicate that PGF2alpha, 1-15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF2alpha, 1-15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF2alpha.

Abortion, Induced↗
PubMed1976

Effect of vaginally administered 15(S)15-methyl-PGF2alpha on egg transport and fertility in rabbits.

The effects of vaginal suppositories containing 1.0 mg of 15[S]15-methy-PGF2alpha on oviductal motility, egg transport, and fertility were determined in rabbits. Suppository treatment caused a significant increase (P less than 0.02) in the amplitude of oviductal contractions, and a decrease in the frequency of contractractions (P less than 0.04). Altered oviductal motility persisted for an average of 2 hr after treatment. Treatment with 1, 2, or 3 suppositories at various times after ovulation caused a significant reduction in the number of eggs located in the oviducts (P less than 0.025). There was, however, a great deal of variation in egg recovery in treated animals (range 0 to 100%). Treatment of mated rabbits during the time of tubal egg transport caused a significant reduction in the number of Day-12 implants (P less than 0.05). The percentage of corpora lutea represented by Day-12 implants was similar to egg recovery rates in animals similarly treated. The treatment had no effect on fetal survival from Day 12 to 28 of pregnancy. The decrease in fertility caused by these vaginal suppositories is presumably due to the stimulatory effect on oviductal motility which accelerates tubal transport of the embryos into the uterus. Embryos that arrive in the uterus prematurely probably do not implant and degenerate or are expelled.

Animals↗
PubMed1976

Peripheral plasma progesterone during egg transport in the rabbit.

Peripheral plasma progesterone concentrations were measured in New Zealand rabbits every 6 hr beginning 12 hr before and continuing until 96 hr after either natural mating, hCG injection, or saline injection. The number of ovulation points in naturally mated animals (9.3 +/- 0.6, mean +/- SE) was not significantly different from that in hCG-injected animals (8.6 +/- 1.5). There was a surge in progesterone secretion following both mating and hCG injection. Plasma progesterone concentrations reached a peak prior to ovulation and then fell to basal levels at the time of ovulation. Beginning at approximately 30 hr after the ovulation-inducing stimulus, there was a progressive, significant (P less than 0.001) increase in plasma progesterone concentration, which continued for the duration of the sampling period. The initiation of the postovulatory increase in progesterone secretion corresponds temporally with the movement of eggs from the ampullary-isthmic junction into the isthmus. The progressive increase in plasma progesterone between 30 and 72 hr after the induction of ovulation corresponds with the gradual movement of eggs through the isthmus into the uterus. The data suggest that movement of eggs through the oviductal isthmus is influenced by the postovulatory secretion of progesterone.

Animals↗
PubMed1976

Evaluation of vaginal delivery systems containing 15[s]15-methyl PGF2alpha methyl ester.

Silicone vaginal delivery systems containing 15[S]15-methyl-PGF2alpha methyl ester have been evaluated in vitro, and in vivo in the rhesus monkey. Three types of vaginal devices have been formulated to contain different concentrations of drug. The cumulative amount of 15[s]15-methyl-PGF2alpha methyl ester released in vitro from a planar silicone rubber matrix was dependent upon the initial loading dose of the prostaglandin. Drug-containing vaginal rings were evaluated in early pregnant and mid-trimester pregnant monkeys. Within 10 min after ring administration there was an increase in the amplitude and frequency of contractions. In mid-trimester pregnant animals there was an initial increase in plasma progesterone and then a decrease following treatment, while there was a progressive decrease in plasma progesterone in early pregnant animals. All 6 mid-trimester pregnant monkeys treated with vaginal rings aborted. Pregnancy was terminated in 4 of 5 early pregnant monkeys treated with vaginal rings. Blood levels of 15-methyl-PGF2alpha rose rapidly to attain a peak 1 hr after treatment with vaginal rings. After the peak, plasma levels of 15-methul-PGF2alpha declined to a plateau which was fairly constant between 2 and 8 hr. Vaginal silicone-gelatin laminates containing 15[s]15-methyl-PGF2alpha methyl ester were also effective in causing an increase in uterine muscle activity and terminating pregnancy in mid-trimester in pregnant monkeys. Plasma progesterone also increased shortly after treatment in these animals, and then declined after the peak at 8 hr. The plasma profile of 15-methyl-PGF2alpha when animals were treated with these vaginal laminates was different from that observed following ring treatment. In pregnant animals the concentration of 15-methyl-PGF2alpha rose more slowly following laminate insertion, and the peak values were considerably less than those following ring treatment. Vaginal devices used in monkeys and humans caused plasma concentrations of 15-methyl-PGF2alpha that were generally lower than those observed in monkeys treated with either vaginal rings or laminates. These studies have demonstrated that silicone vaginal delivery systems containing 15[S]15-methyl-PGF2alpha methyl ester result in sustained and fairly constant plasma levels of 15-methyl-PGF2alpha, and terminate both 1st- and 2nd-trimester pregnancies in the monkey. The vaginal device offers the possibility for self-administration of PGs for early pregnancy termination and menstrual cycle regulation.

Abortion, Induced↗
PubMed1975

Prostaglandins in rabbit blastocyst.

Rabbit blastocysts recovered at 144 hours post coitum contained the prostaglandins F and E-A. We suggest that one or more of these prostaglandins act as mediators in blastocyst steroidogenesis. (In another study we have demonstrated steroidogenesis in rabbit blastocysts).

Animals↗
PubMed1975

Effects of prostaglandins on oviductal motility and egg transport.

The effects of prostaglandins (PGs) on muscular activity of the oviductal isthmus and on the rate of tubal egg transport are reviewed. In consideration of the available data a mechanism by which PGs contribute to the physiological control of egg transport is suggested. In vivo experiments have demonstrated that E-series PGs relax while F-series PGs stimulate muscular activity of the oviduct in humans, subhuman primates and rabbits. These effects are mutually antagonistic. The response of oviductal muscle to PGs appears to be affected by ovarian steroids; progesterone increases the response to PGE1 and decrease the response to PGF2alpha. Oviductal tissue concentrations of PGF increase in a distal to proximal sequence following ovulation-induction in the rabbit. Also, proximal isthmus binding of PGE1 t tended to be greater in 72-hour pregnant rabbits than in estrous rabbits, while binding of PGF2alpha was greater in estrous than in 72-hour pregnant animals. It is suggested that the preovulatory increase in ovarian estradiol secretion stimulates PGF synthesis in the oviductal tissue in a sequential fashion, the peak value occurring when the oviductal isthmus is most sensitive to stimulation by PGF2alpha. The changes in tissue concentration of PGF and in sensitivity to PGF2alpha could contribute to occlusion of the isthmus and prevent premature passage of eggs into the uterus. An increase in ovarian progesterone secretion after ovulation may decrease tissue PGF, decrease the response to PGF2alpha stimulation, and increase the response to PGF1. These changes may then allow a progressive movement of eggs through the isthmus into the uterus. Several questions regarding this proposed mechanism remain unanswered.

Animals↗