Decrease In Plasma Progesterone Research Articles

Effect of oestradiol benzoate or luteinizing hormone on levels of progesterone in the pseudopregnant rat.

The present study was concerned with a possible involvement of LH in process of functional luteolysis in the pseudopregnant rat. Daily injections with 2 micrograms ovine LH during pseudopregnancy reduced peripheral and ovarian levels of progesterone in intact and hysterectomized rats and in hypophysectomized rats with a pituitary transplant under the kidney capsule. However, a daily dose of 10 micrograms LH did not alter the levels of progesterone. A short-lasting decrease in plasma progesterone occurred when endogenous levels of LH were temporarily raised in pseudopregnant rats by a single injection of LH releasing hormone (LH-RH). Treatment with LH or LH-RH, however, did not shorten the duration of pseudopregnancy. Daily treatment of pseudopregnant rats with with 5 or 20 ng oestradiol benzoate, but not with 1000 ng, decreased plasma levels of progesterone. On the other hand, daily treatment with oestradiol benzoate did not affect plasma progesterone in pseudopregnant rats which were hypophysectomized and had an ectopic pituitary gland. Plasma levels of LH were not increased in the animals receiving 5 or 20 ng oestradiol benzoate daily, suggesting that the effect of oestradiol benzoate on plasma progesterone is not through an enhanced secretion of LH. Treatment with oestradiol benzoate did not affect the duration of pseudopregnancy. In conclusion, low doses of LH can reduce peripheral levels of progesterone during pseudopregnancy, but it seems improbable that LH is involved in the process of functional luteolysis. Furthermore, low doses of oestradiol benzoate can also decrease plasma progesterone, but the mechanisms involved are still not understood.

Receptor-mediated gonadotropin action in the ovary. Rat luteal cells preferentially utilize and are acutely dependent upon the plasma lipoprotein-supplied sterols in gonadotropin-stimulated steroid production.

cells responded to luteinizing hormone, human chorionic gonadotropin, isoproterenol, and cholera toxin with an increase in progesterone and cyclic AMP responses. Administration of 4-aminopyrazolo(3,4~)p~midine (4-UP) (12.5 mgfkg body weight) for 3 consecutive days reduced the circulating cholesterol level from 47.32 2 1.12 mg/dl to 8.16 & 0.43 mg/dl and plasma progesterone from 280 f 26 ng/ml to 96 k 6 ng/ ml. Cellular sterol ester content was reduced to 25% following 4-APP injection. Injection of drug also produced a small but significant decrease in luteal cell free cholesterol. Treatment of rats with 4-APP also reduced the in vitro basal and hormone-stimulated progesterone production. This treatment showed no effect on luteal cell ‘251-human chorionic gonadotropin binding or gonadotropin and cholera toxin stimulated cyclic AMP synthesis. Exposure of luteal cells isolated from control and 4-APP injected groups to homologous or heterologous lipoproteins (low and high density lipoproteins) produced significant stimulation in steroidogenesis, both under basal conditions and in response to gonadotropins. Similarly, luteal cells isolated from 4APP-injected rats incorporated [3H]cholesterol from [3~~cholesteryl linoleate into progesterone at a much faster rate compared to control cells, and this effect was further enhanced in response to human chorionic gonadotropin. Injection of rats with Triton WR 1339 (1 g/kg body weight) resulted in a 10-fold increase in circulating cholesterol level. This treatment, however, produced a significant decrease in plasma progesterone and cyclic AMP and progesterone responses in isolated cells. The inhibitory effect of Triton injection on steroidogenesis could not be reversed by lipoprotein addition. These studies suggest that rat luteal cells are acutely dependent upon exogenous lipoprotein cholesterol for the maximum expression of steroidogenic response.

Inhibition of Progesterone Secretion During the Luteal Phase by Two Luteinizing Hormone-Releasing Hormone Agonists in Macaca fascicularis

The administration of 200 microgram of the potent luteinizing hormone-releasing hormone (LHRH) agonist [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide on day 6 following the plasma estradiol peak to 11 female monkeys (Macaca fascicularis) during two consecutive menstrual cycles decreased plasma progesterone levels by 40.0% +/- 3.9% as compared with previous control cycles. The plasma estradiol profile and the cycle length were not affected significantly by the treatment. Similar results were obtained with 25 microgram of [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide administered to one monkey at the same period of the cycle, such treatment leading to a 41% inhibition of circulating progesterone levels. Although plasma progesterone levels were still reduced in the two post-treatment cycles in monkeys treated with the high dose (200 microgram) of [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide, the recovery cycle was normal after the administration of a lower dose (25 microgram) of [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide. The M. fascicularis monkey thus appears as a valid model with which to study the inhibitory effects of LHRH agonists on luteal function.

Unilaterally ovariectomized pregnant mice: dieldrin induction of the hepatic monooxygenases and plasma progesterone levels.

Plasma progesterone, pregnancy maintenance, gestation period, and litter size were measured in mice unilaterally ovariectomized on day 6 of pregnancy (plug day = day 0) and then treated daily with dieldrin (2 mg kg-1, p.o.). By days 15--16, dieldrin had reduced the pentobarbital sleep time by 54% (P < 0.05), increased the liver mass by 8% (P < 0.05), and increased hepatic microsomal cytochrome P-450 by 66% (P < 0.05). However, the levels of plasma progesterone in the hemiovariectomized, dieldrin-treated mice were not different from those in the hemiovariectomized controls. Other experiments showed that hemiovariectomy decreased plasma progesterone by about 25%. Moreover, hemiovariectomy increased the frequency of premature delivery but it did not affect litter size; dieldrin treatment did not alter these effects. The failure of the induction to reduce plasma progesterone could result from (1) increased progesterone synthesis compensating for its elevated metabolism or (2) no (net) increase in progesterone metabolism.

Effect of dose and time of injection of prostaglandin F 2α in cycling ewes

A study was done to evaluate the efficacy of graded doses of prostaglandin F 2α (PGF 2α) to induce regression of the corpus luteum and hence estrus, in cycling ewes when given on various days of the estrous cycle. One hundred cycling cross-bred ewes were observed twice daily (08:00 and 20:00 h) for marking by raddled vasectomized rams. After estrus was confirmed in marked ewes by assay of plasma progesterone concentration, the ewes were treated in pairs with 0, 5, 10, 15 or 20 mg PGF 2α on day 2, 3, 4, 7, 8, 9, 12, 13, 14 or 15 of an estrous cycle and then exposed to a raddled ram of known libido and fertility. Plasma progesterone levels were determined on the day of, and on the day following PGF 2α-treatment to monitor luteal function. Ewes marked between one and five days after treatment and having a decrease in plasma progesterone were considered to have responded to the treatment. The percentages of ewes responding were 10, 35, 60, 70 and 95 to doses of 0, 5, 10, 15 and 20 mg PGF 2α respectively. Differences due to dose were significant (P < 0.01) with the two higher doses being more effective. There were differences due to the day of injection, with treatments on days 2 and 3 being less effective.

Oxytocin receptors and parturition. III. Increases in estrogen receptor and oxytocin receptor concentrations in the rat myometrium during prostaglandin F2 alpha-induced abortion.

Marked elevations in the concentrations of receptors for estrogen (E) and oxytocin (OT) in the rat myometrium occur during spontaneous labor. These increases appear to be correlated with a decrease in plasma progesterone (P). In this study we sought to determine if these same changes in plasma steroid and myometrial receptor concentrations can be made to occur prematurely when pregnancy is terminated with prostaglandin Fα, (PGF2α). The administration of PGF2α to rats on day 18 of pregnancy resulted in premature delivery on day 20. PGF2α-induced labor was associated with a rise in the concentration of myometrial receptors for E and OT. The administration of P to these rats inhibited the increases in concentration of receptors for E and OT on day 20 and prevented premature delivery. In contrast, PGF2α administration on day 15, when plasma P is near maximal, resulted in marginal changes in myometrial receptor concentrations and in uninterrupted pregnancy. PGF2α treatment on day 10 increased the concentration...

Half-Life of Plasma Progesterone in Turkey Layers and Non-Layers

Large White turkey layers and non-layers were used in this study of progesterone half-life. The half-life was determined from regression of linear decrease in plasma progesterone after a single injection of unlabelled progesterone. Blood samples were collected every 10 min for a period of 2 hr after hormone injection. Radioimmunoassay was used to measure progesterone in all plasma samples.The half-life of plasma progesterone in layers (63.7 ± 3.3 min.) was significantly lower than in non-layers (91.8 ± 6.0 min.). Our results indicated that progesterone synthesis or release in turkey layers could have been much greater than non-layers. This would also suggest that the uptake of progesterone by receptors in target tissues could be much more in layers than non-layers.

Relationship of luteal blood flow and corpus luteum function in pseudopregnant rats.

An experiment was conducted to examine whether blood flow to corpora lutea may regulate luteal function as judged from plasma levels of progesterone (P) in mature pseudopregnant rats. 141Ce-labeled microspheres (14.1 +/- 0.8 micrometer diam) were used to measure cardiac output and organ and tissue blood flow in rats on days 6, 8, 10, and 12 of pseudopregnancy and in proestrus following luteal regression. The mean arterial blood pressure and cardiac output were similar among all groups of rats. Although a significant (P less than 0.05) decrease in plasma P was observed in rats on day 12 of pseudopregnancy, no change in luteal blood flow or distribution of ovarian blood flow to the corpora lutea was seen at this stage of pseudopregnancy when compared to day 8 or 10 of pseudopregnancy. However, a significant decrease (P less than 0.05) in luteal blood flow was seen in proestrous rats. Because a decrease in plasma progesterone preceded the decrease in luteal blood flow, it was concluded that physiological luteal regression may not be initiated by a reduction of blood flow to the corpus luteum.

Plasma gonadotrophins and progesterone concentrations during various degrees of underfeeding in pregnant mice.

Daily reduction of the normal (ad libitum) food consumption by as little as 35% significantly reduced (P less than 0.05) the percentage of mice with implantation sites at Days 7 and 9 of gestation. Underfeeding decreased body weight and reduced the weight of the ovaries and uterus. Plasma progesterone was decreased (P less than 0.05) as dietary intake was restricted and was associated with regression of the corpora lutea. No significant alterations in the plasma values of LH and FSH were observed in mice underfed between Days 1 and 9 of pregnancy. The decrease in plasma progesterone in the absence of reduced LH values may indicate that progesterone secretion between Days 5 and 9 of gestation is not controlled solely by LH.

Prostaglandin F2a-Induced Prolactin Release and Luteolysis in the Goat

Injection of prostaglandin F2 alpha (PGF2 alpha) initiated a significant increase in plasma prolactin levels in all goats except those in anoestrus. Luteolysis occurred in non-pregnant goats during the mid luteal phase when the goats were given PGF2 alpha either with or without the suppression of prolactin release by bromocryptine (CB154). Luteolysis and subsequent parturition also occurred in pregnant goats in mid and late gestation after PGF2 alpha injection, with an associated release of prolactin and decrease in plasma progesterone. Acute prolactin release in response to injection of thyrotrophin releasing factor may have had a transient effect on plasma progesterone levels, but did not appear to be luteolytic in either pregnant or non-pregnant goats.

Plasma Progesterone Assays in Superovulated Cattle

Plasma progesterone was measured in 14 normally cycling heifers and cows subjected to non-surgical recoveries of embryos. A radioimmunoassay (RIA) method was used for progesterone determination. The average progesterone concentration increased from 7.5 to 11.6 ng/ml in 8 of the animals following treatment with PMSG on day 8–12. Six animals had a decrease from 5.0 ± 2.1 to 3.9 ± 2.5 ng/ml. The overall increase was from 6.4 ± 2.7 ng/ml to 8.3 ± 4.8 ng/ ml. Prostaglandin F2a-analogue (cloprostenol) treatment resulted in a sharp decrease in plasma progesterone followed by a rapid increase to an average of 46.8 ng/ml on day 16. A high degree of variability in this peak value was observed, and it was not correlated with the number of corpora lutea. The superovulatory cycle was generally prolonged. The heat following the superovulatory treatment was silent, and a typical ovarian resting period was observed during which the progesterone concentration remained low and the ovaries small.

Prostaglandin E 1 and F 2α specific binding in bovine corpora lutea: Comparison with luteolytic effects

Preliminary characterization indicated the presence of separate prostaglandin (PG)E 1 and (PG)F 2α binding sites in membrane fractions prepared from bovine corpora lutea. These differ in the rate and temperature dependence of the specific binding. Equilibrium binding data indicate the apparent dissociation constants as 1.32 × 10 −9M and 2.1 × 10 −8M for PGE 1 and PGF 2α, respectively. Competition of several natural prostaglandins for the PGE 1 and PGF 2α bovine luteal specific binding sites indicates specificity for the 9-keto or 9α-hydroxyl moiety, respectively. Differences in relative ability to inhibit 3H-PG binding were found due to sensitivity to the absence or presence of the 5,6-cis-double bond as well. Bovine luteal function was affected following treatment of heifers with 25 mg PGF 2α as measured by reduced estrous cycle length, decreased corpus luteum size and significantly decreased plasma progesterone levels. In contrast, treatment with 25 mg PGE 1 resulted in cycle lengths comparable to those of non-treated herdmates with no apparent modification in corpus luteum size. However, plasma progesterone levels were increased significantly following PGE 1 treatment compared to pretreatment values. In so far as data obtained in vitro on PGF 2α relative binding affinity to the bovine CL can be compared to data obtained independently in vitro on PGF 2α induced luteolysis in the bovine, PGF 2α relative binding to the CL and luteolysis appeared to be associated. By similar reasoning, there was no apparent relationship between PGE 1 relative binding affinity in the luteal fractions and luteolysis in estrous cyclic cattle.

Prostaglandin E 1 and F 2α specific binding in bovine corpora lutea: Comparison with luteolytic effects

Preliminary characterization indicated the presence of separate prostaglandin (PG)E 1 and (PG)F 2α binding sites in membrane fractions prepared from bovine corpora lutea. These differ in the rate and temperature dependence of the specific binding. Equilibrium binding data indicate the apparent dissociation constants as 1.32 × 10 −9M and 2.1 × 10 −8M for PGE 1 and PGF 2α, respectively. Competition of several natural prostaglandins for the PGE 1 and PGF 2α bovine luteal specific binding sites indicates specificity for the 9-keto or 9α-hydroxyl moiety, respectively. Differences in relative ability to inhibit 3H-PG binding were found due to sensitivity to the absence or presence of the 5,6-cis-double bond as well. Bovine luteal function was affected following treatment of heifers with 25 mg PGF 2α as measured by reduced estrous cycle length, decreased corpus luteum size and significantly decreased plasma progesterone levels. In contrast, treatment with 25 mg PGE 1 resulted in cycle lengths comparable to those of non-treated herdmates with no apparent modification in corpus luteum size. However, plasma progesterone levels were increased significantly following PGE 1 treatment compared to pretreatment values. In so far as data obtained in vitro on PGF 2α relative binding affinity to the bovine CL can be compared to data obtained independently in vitro on PGF 2α induced luteolysis in the bovine, PGF 2α relative binding to the CL and luteolysis appeared to be associated. By similar reasoning, there was no apparent relationship between PGE 1 relative binding affinity in the luteal fractions and luteolysis in estrous cyclic cattle.

Suppression of uterine activity and abortion by inhibition of prostaglandin synthesis

The premise had been examined that the evolution of uterine activity, provoked by progesterone (P)-deficiency and consequent prostaglandin (PG)-dominance, can be suppressed in patients by inhibiting PG-synthesis. In 20 midtrimester pregnant women: P-deficiency, evolution of intrauterine pressure (IUP), oxytocin response (OR) and abortion, had been induced by the hypertonic saline technique and the changes in P and E 2 levels and in IUP and OR measured sequentially. According to a “double blind” protocol, 10 volunteers received placebo, while another 10 were treated during 14 hours with 1050 mg naproxen ⋆ , an inhibitor of PG-synthesis. ⋆ In this study naprozen-NA has been used Significant decrease in plasma progesterone (P < 0.001) and estradiol 17β (P < 0.02) preceding clinical progress in abortion demonstrated that hypertonic saline suppressed the endocrine function of the feto-placental unit in both Groups of patients. However, in spite of a 40% reduction in the P-levels of the Experimental Group (at a time when the Controls aborted) the evolution of IUP, OR and abortion in the naproxen treated patients had been delayed by ∼30 hours. This significant delay in all the measured parameters (P < 0.001) is evidence that inhibition of PG-synthesis prevents the endogenous activation of the uterus in patients, as it does in animal “models”.

Decreased endometrial blood flow and plasma progesterone level after instillation of 10 μg prostaglandin F 2α into the lumen of the uteri of rhesus monkeys

Instillations of 10 μg prostaglandin F 2α were performed once a week for four weeks into the lumina of the uteri of three nonsedated rhesus monkeys. Before and immediately after the instillation the endometrial blood flow was measured with the 133Xenon clearance technique. Plasma progesterone was measured by a radioimmunoassay method in blood samples taken before and 20 hrs after the instillation. The results showed a significant (p = 0.01) decrease to 39% (mean) of the original blood flow and a decrease to 23% (mean) of the original plasma progesterone content. The results also indicated a conditioning of the monkeys, causing a decreased endometrial blood flow, to the prostaglandin treatment from the third week on. The decrease of the endometrial blood flow may be caused by a local PG 2α-induced vasoconstriction. The decrease in plasma progesterone may be a direct luteolytic effect of prostaglandin F 2α, or it may be caused by a uterine factor, the secretion of which is stimulated by the relative ischaemia lasting at least 15 mins.

Prostaglandin E 2 : analysis of effects on pregnancy and corpus luteum in hamsters and rats.

ABSTRACT Effects of prostaglandin (PG) E2 on some reproductive processes of hamsters and rats were studied. The PG exerted antifertility effects in either species although it was 4–10 times less potent than PGF2α. Antifertility doses of PGE2 caused morphological degeneration of corpora lutea, induced fresh ovulations during the course of the treatment, significantly decreased peripheral progesterone levels and inhibited development of deciduomata in response to trauma. Both pregnancy and decidual growth could be maintained by simultaneous administration of exogenous progesterone. PGE2 also decreased plasma progesterone concentration in pseudopregnant-hysterectomized hamsters although the decrease was not significant when compared with intact pregnant or pseudopregnant hamsters. PGE2 produced no demonstrable effects on egg transport in hamsters but may have induced delayed implantation in rats by causing tubal retention of zygotes. The antifertility doses of PGE2 but not of PGF2α inhibited implantation of a proportion of blastocysts as studied by the Pontamine blue reaction and adversely affected the spacing mechanism of blastocysts in the uterus significantly reducing the distance between the adjacent implantation sites. When PGs E2 and F2α were given together to pregnant rats in doses which were virtually ineffective individually, the combined treatment caused loss of pregnancy. Administration of PGE2 to near term hamsters produced premature littering but oxytocin in doses tried proved inactive. Antifertility doses of PGE2 produced diarrhoea in rats but not in hamsters. The results demonstrate that PGE2 shares the luteolytic property of PGF2α but in addition possesses several other properties not known to be shared by PGF2α.

Interaction between prolactin, LH, neurohypophysial hormones and hysterectomy on luteal function in rats.

Functional corpora lutea (CL), which were capable of sustaining high levels of plasma progesterone, were maintained in hypophysectomized rats by transplantation of the pituitary or by daily treatment with exogenous prolactin. Treatment of autografted rats with exogenous LH (20 μg/day) for 6 days greatly reduced the plasma concentration of progesterone. Injections of LH to autografted rats for only 2 days markedly reduced progesterone in one half of the experimental animals. Even though exogenous LH was clearly luteolytic in autografted rats, the response in prolactin-treated, hypophysectomized rats depended upon the exact timing of each LH injection relative to each prolactin injection. Exogenous LH for 6 days greatly decreased plasma progesterone when each LH injection (1100 and 2000 hr) occurred 3 hr after a prolactin injection (0800 and 1700 hr). Injection of LH 3 hr before each prolactin injection had no effect on the concentration of plasma progesterone which was the same as in controls treated only with prolactin. Simultaneous injection (0800 and 1700 hr) of LH and prolactin produced an intermediate effect characterized by a slight reduction in progesterone concentration in some rats. The permissive effects of endogenous prolactin and of exogenous prolactin injected 3 hr before LH were manifested in the ability of exogenous LH, given for several days, to induce functional luteolysis and decrease plasma progesterone. Treatment of autografted rats with large dosages of neurohypophyseal hormones did not affect the plasma concentration of progesterone. Hysterectomy of pituitary intact, pseudopregnant rats had no effect on plasma progesterone on days 8 and 10. Plasma progesterone in hysterectomized animals remained elevated on days 12 and 14 whereas the levels in sham-operated controls declined.

Plasma progesterone in pregnancy interrupted by the intrauterine injection of hypertonic saline.

ABSTRACT Plasma levels of progesterone (pregn-4-ene-3,20-dione) were measured in nineteen pregnant patients following intra-amniotic injection of hypertonic saline between the 13th and 20th week of gestation. A significant decrease in the plasma progesterone was found 5, 10, and 24 hours following the injection. However, the decrease in plasma progesterone was not correlated to the time interval between the saline-injection and the onset of clinical labour (correlation coefficient 0.019).

Plasma progesterone levels during saline-induced abortion.

ABSTRACT Thirty-three normal, midtrimester patients were given injections of hypertonic saline, and 5 similar patients received injections of isotonic saline by intra-amniotic administration. During a 20 hr observation period plasma progesterone levels of patients treated with isotonic saline remained relatively constant, and no clinical progress was evident. In contrast, those patients receiving hypertonic saline showed a significant decrease in plasma progesterone to levels which averaged 53% below the initial value before abortion. 20α-Hydroxypregn-4-en-3-one (20α-OH-P) levels also decreased following hypertonic saline administration. These findings are consistent with earlier conclusions that progesterone withdrawal may be causally related to the physiological and clinical consequences of hypertonic saline treatment and that the effect may be mediated by a decrease in the placental biosynthesis of progesterone.

Plasma progesterone levels in normal pregnancy, labor, and the puerperium: II. Clinical data

One hundred and seventy-two plasma progesterone determinations were performed in normal pregnancy, labor, and the puerperium. One hundred and nineteen of the assays were done on isolated samples; 53 of the assays were done in 11 serial studies. While the concentration of progresterone in peripheral blood increased progressively with advancing pregnancy, no apparent decrease in the hormone level occurred at or near the onset of labor or during its progress. A significant decrease in plasma progesterone one hour after the delivery of the placenta continued to decline to menstrual cycle levels by 72 hours post partum.