Guillermo Valenzuela

Immunoreactive gonadotropin-releasing hormone level in maternal circulation througout pregnancy

Immunoreactive gonadotropin-releasing hormone was quantitated in maternal blood. Circulating levels of gonadotropin-releasing hormone were found to be significantly higher during pregnancy than in nonpregnant cycling women. The highest concentrations of gonadotropin-releasing hormone immunoreactivity were observed in the first half of pregnancy with values at 20 to 42 weeks being significantly lower. A correlation with placental human chorionic gonadotropin-releasing hormone concentrations and maternal circulating gonadotropin-releasing hormone levels was noted. Four pregnancies that resulted in premature labor and/or delivery had very low circulating maternal gonadotropin-releasing hormone concentrations, possibly reflecting placental dysfunction in these cases.

Accelerated ovum transport in rabbits induced by endotoxin 1. Changes in prostaglandin levels and reversal of endotoxin effect

Abstract The effect of endotoxin ( Salmonella enteritidis -Boivin) on ovum transport in the rabbit was examined. A dose of 10 μg/kg intravenously (iv) given 24 h after an injection of human chorionic gonadotrophin (hCG) to induce ovulation caused expulsion of 87% of ova from the oviduct within 24 h. The ED50 and 95% probability limits were 3.1 (2.38–4.03) μg/kg. A dose of 20 μg/kg given at 24 h after hCG exerted its effect on ovum transport within 4 h. Concurrent treatment with indomethacin completely prevented the effect of endotoxin on ovum transport. Endotoxin caused an increase of prostaglandin-like material (PG) E, measured by radioimmunoassay, in uterine vein blood within 35 min and PGE levels continued to rise until 3 h after endotoxin and remained elevated until 8–9 ½ h. PGF in uterine vein blood was not elevated until 90 min after endotoxin and then increased more rapidly than PGE during the next 2.5 h: it was still elevated at 8–9 ½ h. The ratio of PGF:PGE in uterine vein blood decreased from 3:1 in 24 h control samples to 1:1 at 1 h after endotoxin, and then increased rapidly exceeding 5:1 at 2 h. In animals given both indomethacin and endotoxin PG levels in uterine vein blood declined. Phenoxybenzamine partially prevented the effect of endotoxin on ovum transport and in animals so treated PGE levels in uterine vein blood increased similarly to those in animals receiving endotoxin alone, but PGF values, while elevated, were suppressed compared to those in endotoxin animals and the PGF:PGE ratio never exceeded 2:1. It is concluded that endotoxin induces accelerated ovum transport by causing an initial relaxation of the oviductal isthmic musculature due to PGE dominance followed by stimulation of oviductal circular musculature due to PGF dominance.

Uterine venous, peripheral venous, and radial arterial levels of prostaglandins E and F in women with pregnancy-induced hypertension

Patients with pregnancy-induced hypertension have higher prostaglandin (PG) F concentrations in radial arterial blood (0.39 +/- 0.03 ng/ml) than control subjects (0.24 +/- 0.03 ng/ml) and higher (PGE plus PGF) concentrations in uterine venous blood obtained at the time of cesarean section (1.62 +/- 0.18 versus 1.03 +/- 0.12 ng/ml in the control group). The present results suggest that both PGE and PGF production by the uterus in patients with pregnancy-induced hypertension is increased but that catabolism of PGF by the lung is compromised; this permits larger quantities of the vasoconstrictor PG to pass into the systemic circulation, where it may cause hypertension directly or indirectly, by association with other vasoactive substances.

Effect of inhibitors of prostaglandin synthesis and metabolism on ovum transport in the rabbit.

Several drugs known to affect prostaglandin synthesis, release, or metabolism have been tested for their effects on ovum transport in the rabbit after systemic or local administration. Acceleration of transport was obtained with several drugs; among the most effective were benzydamine, a blocker of thromboxane production, and L11204, an inhibitor of prostaglandin metabolism.

Prostaglandin Production by Rhesus Monkey Corpora Lutea in Vitro: Effects of Estrogen Administration

Luteolysis was induced in normal cycling rhesus monkeys (Macaca mulatta) by daily administration of estradiol cypionate (50 μg/kg) from day 1 to 7 postovulatory (controls received vehicle). Luteectomy was performed after treatment, using microsurgical techniques and minimal manipulation. Serum progesterone concentrations did not demonstrate characteristic luteal rise in estrogen‐treated animals as compared to controls. Estrogen treatment increased prostaglandin F2α/ E ratio produced in vitro by the corpora lutea twofold compared to controls. These results support our previous observations that luteolysis in the rhesus monkey is associated with increased production of prostaglandin F2α and decreased production of prostaglandin E by the corpus luteum.

Contraceptive properties of endotoxin in rabbits.

Endotoxin derived from Salmonella enteritidis-Boivin at a dose of 20 micrograms/kg intravenously interfered with follicular rupture normally induced by human chorionic gonadotropin (hCG) in rabbits. This action was greatest when the endotoxin was given 5 to 6 hours after the administration of hCG. The failure of follicular rupture resulted in entrapment of ova. Endotoxin (5 micrograms/kg) given intravenously to rabbits on day 4 of pregnancy resulted in failure of implantation. Indomethacin (2 micrograms/kg) given intramuscularly concomitantly was unable to reverse this action. Endotoxin (5 micrograms/kg) given intravenously to rabbits on day 8 of pregnancy had an immediate lethal action on embryonic development, and this effect was inhibited by concomitant indomethacin treatment. Nevertheless, most fetuses died after the indomethacin treatment. Whether this was due to a direct toxic action of indomethacin or to a secondary action of endotoxin not blocked by indomethacin is not clear. Endotoxin did not exert its antifertility actions through a luteolytic mechanism.

Accelerated ovum transport in rabbits induced by endotoxin II. Changes in oviductal smooth muscle activity

Oviductal mortility, measured with open-ended perfused catheters in anesthetized animals injected with human Chorionic Gonadotropin (hCG), is depressed 2 h following endotoxin injection and returns to control levels by 3 h after endotoxin injection. This decrease in motility is prevented by indomethacin. Endotoxin did not affect spontaneous or phenylephrine (PE)-induced contractions of oviduct when it was added to the bathing medium of in vitro tissues. Oviductal segments removed 2 h after endotoxin (26 h after hCG) showed electrical activity confined to the ampullary-isthmic-junction (AIJ), where ova were located; the dose-response curve for PE was shifted to the right and the maximum contraction was depressed. Activity of tissues removed 4 h after endotoxin more closely resembled control tissues except that the maximum contraction to PE was depressed, ova had passed out of the oviduct and a proovarian bias in the isthmus was not present. The response of the oviduct to prostaglandins (PGs) in vivo is critically dependent on the previous exposure to PGs. In endotoxin-treated animals PGE then PGF levels increase and the decrease in motility coincides with increased PGE levels, but accelerated ovum transport with the return of motility and activation of the isthmus.

Endotoxin-induced acceleration of ovum transport in rabbits.

Salmonella enteritidis-Boivin endotoxin (1–20 μg/kg) induced accelerated oviductal ovum transport in rabbits in a dose-related manner. Indomethacin prevented this effect. Levels of prostaglandin E and F in uterine vein blood increased following endotoxin injection.

Comparison of the effects of prostaglandins D2, F2α and E1 on spontaneous contractions of rabbit oviduct

The effects of PGD2, PGF2alpha and PGE1 were studied on the circular muscle of post-ovulatory rabbit oviducts in vitro. PGE1 inhibited spontaneous contractile activity. Lower concentrations of PGD2 and PGF2alpha were stimulatory and higher concentrations were inhibitory. Since PGD2 may be produced in the oviduct, any hypothesis concerning the role of prostaglandins in the control of oviductal motility and ovum transport should include PGD2 as well as PGFs and PGEs.

Platelets bind to rhesus monkey corpora lutea and stimulate its prostaglandin synthesis**Supported in part by NIH grants HD 14048 and 1P30 HD 10202 (Radioimmunoassay and Bioassay Cores).

The in vitro production of different prostaglandins (PGs) was studied in rhesus monkey corpora lutea incubated with labeled arachidonic acid. The percentage of conversion of the arachidonic acid to all the PGs identified was similar, but the addition of platelet lysates caused at least a sevenfold stimulation of all PGs by the corpora lutea, the greatest stimulation in production occurring in the area corresponding to PGE2 and 15-keto-PGF2 alpha. Adipose tissue by itself produced more PGs than corpus luteum (CL); but, in contrast, such production was inhibited by addition of platelet lysates to the levels of conversion of the unstimulated CL. 125I-labeled platelets bound specifically to monkey CL, but not to adipose tissue. The interaction of the platelets with the CL in the formation of PGs may be of significance in the regulation of the luteal life span.