Role of ovarian steroid hormones in the regulation of adenylate cyclase during early progestation

The hormonal regulation of uterine adenylate cyclase (AC) was measured in the rat by radiochemical analysis. Animals made pseudopregnant by cervical stimulation were ovariectomized on Day 1 (the first appearance of leukocytes in the vaginal smear) and injected for 6 days with sesame oil, 0.1-10.0 micrograms estrone, 2.0 mg progesterone, or 1.0 microgram estrone + 2.0 mg progesterone. AC activity in ovariectomized controls remained at basal levels (2.8-3.3 pmol cAMP formed/min X mg protein). The injection of progesterone did not alter AC activity significantly, but estrone increased AC activity during Days 3-5, and the response (5-17 pmol) was dose dependent. The action of estrone was not inhibited by progesterone. The present experiments revealed: a) AC from estrone-treated rats was activated 2- to 4-fold by 10 mM NaF; b) following treatment with estrone + progesterone, AC was activated 2- to 3-fold by a trauma to the uterus; c) unlike the response to fluoride, the effect of trauma was temporally limited to Day 4; and d) when AC was activated by trauma, no further increase was elicited by NaF. The data indicated that the transient sensitivity of AC to activation by trauma on Day 4 in E+P-treated rats was identical to that in intact rats and paralleled the normal timing of uterine sensitivity to decidual induction.     

Action of prostaglandin F2alpha on pregnancy in hamsters: luteolytic and extra-ovarian effects.

Pregnancies in hamsters may be terminated by 10 mug PGF2alpha administered b.i.d. on days 4, k and 6 of gestation. Small (250 mug and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 mug of estrone essentially normalized the gestation; administration of PGF2alpha at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F2alpha on pregnancy in hamsters.     

Effects of gonadotropin-releasing hormone treatment on ovarian steroid production during midpregnancy

During the second half of pregnancy, ovarian testosterone (T) through its conversion to estradiol (E) promotes progesterone (P) synthesis by the ovary which maintains the pregnancy. To determine if the administration of gonadotropin-releasing hormone (GnRH) disrupts pregnancy by suppressing ovarian production of T or its conversion to E, rats were treated from Day 11 through Day 18 of pregnancy with 50 or 100 micrograms/day of GnRH or 1, 5, or 10 micrograms/day of a GnRH agonist (GnRH-Ag; WY-40972) using an osmotic minipump. Rats were bled daily from the jugular vein under light ether anesthesia and on Days 14 or 18 of pregnancy both jugular and ovarian blood samples were obtained. While the GnRH-Ag treatment at the dose of 5 or 10 micrograms/day terminated pregnancy within 48 hr as indicated by vaginal bleeding, 1 microgram/day terminated pregnancy more slowly. Neither dose of GnRH was effective in terminating pregnancy through Day 18. By Day 14, peripheral levels of plasma P in rats treated with 0, 1, 5, or 10 micrograms of GnRH-Ag were 97 +/- 9, 24 +/- 1, 13 +/- 3, and 8 +/- 1, respectively. In the same groups, levels in the ovarian vein were 3205 +/- 633, 1317 +/- 273, 360 +/- 113, and 228 +/- 73 ng/ml. By Day 18, serum P levels in the peripheral circulation and in the ovarian vein were declining even more dramatically. Daily administration of P (4 mg) and E (0.5 micrograms) simultaneously with GnRH-Ag at the dose of 5 micrograms/day from Days 11 through 14 reversed the abortifacient effect of GnRH-Ag and maintained pregnancy indicating that the GnRH-Ag effect is not directly on the uterus. Ovarian vein levels of T on Days 14 or 18 of pregnancy were either not different from controls at 1407 +/- 163 or 1476 +/- 122 pg/ml, respectively, or increased dramatically in certain groups. Ovarian vein levels of E were either not different from controls at 292 +/- 13 pg/ml on Day 14 or increased significantly in rats treated at the dose of 1 microgram/day of GnRH-Ag. However by Day 18, treatment with GnRH-Ag at all doses suppressed ovarian secretion of E. These results suggest that while the GnRH-Ag induces abortion in rats by suppressing ovarian production of P, this abortifacient effect is not due to a fall in ovarian T levels nor to its aromatization to E in the ovary.     

Variation in the responsiveness of female rats to ovarian hormones as a function of preceding hormonal deprivation

Ovariectomized female rats were tested for the display of lordosis behavior 30 days after gonadectomy. They were then tested 7, 14, 21 and 81 days later following estrogen and progesterone treatment. Finally, on Day 88 of the experiment the animals were tested after either estrogen and progesterone treatment or after progesterone alone. The response to estrogen and progesterone treatment was found to be limited on the first test and on the fifth test which occurred after 2 mo without hormone treatment. When hormone treatment was repeated at seven day intervals (Tests 2–4) the tendency to show lordosis increased markedly. On the final test the animals given both hormones showed lordosis, while those which received only progesterone did not. The data suggest that the response to estrogen decreases after estrogen deprivation.     

The effects of paradoxical sleep deprivation on estrous cycles of the female rats

The present purpose was to examine how sleep deprivation affects the estrous cycle of the female rat. Paradoxical sleep-deprived (PSD) adult female Wistar rats were compared to home-cage control (CTRL) on their estrous cyclicity. Forty-four PSD and forty-four CTRL female rats were distributed into 4 subgroups of 11 animals each according to the phase of estrous cycle and were subjected to sleep deprivation for 96 h by the multiple platform technique. After PSD period, vaginal estrous cycles were taken for an additional 9 days. Animals that were submitted to PSD in diestrus phase (PSD-diestrus) had their estrous cycles disrupted during the recovery period by showing a constant diestrus during the first week. As for hormone alterations, progesterone concentrations were statistically higher in PSD-diestrus compared to respective phase control and to PSD-proestrus and PSD-estrus rats while CTRL-metestrus had higher levels than CTRL-proestrus and estrus groups. Testosterone was significantly decreased in PSD-estrus in relation to PSD-proestrus and PSD-diestrus groups and was lower in CTRL-diestrus rats than in home-cage rats in proestrus. In addition, PSD-diestrus phase exhibited higher concentrations of corticosterone and lower estrogen than the respective control rats. These data indicate that PSD may modulate the ovarian hormone release through alterations in hormonal-neurochemical mechanisms.     

Factors subserving the enhancing effect of progesterone on the output of prostaglandin F2 alpha in uteri from ovariectomized rats

The effects of progesterone (P4) and of calcium-ionophore A-23187, on the release of prostaglandins (PGs) E2 and F2 alpha, in uteri isolated from ovariectomized rats and the influences of mepacrine and nifedipine, were explored. The metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF 1 alpha, PGE 2 and PGF2 alpha) in uterine segments from spayed rats, injected or not with P4, was also studied. In all cases ovariectomy was performed 20-25 days prior to sacrifice. One group of spayed rats were injected with 4.0 mg of P4 during two days and sacrificed 24 h after the last injection. The remaining spayed animals were considered as controls. Tissue samples from both groups were incubated for one hour in the absence or in the presence of either A-23187 (1.0 microgram/ml), mepacrine (10(-3) M) or nifedipine (10(-6) M), or a combination of A-23187 plus mepacrine. At the end of the incubating period PGs in the suspending solution were extracted, separated, identified (TLC) and quantitated. The metabolism of 14C-AA into different prostanoids was explored in uterine segments from spayed rats, injected or not with P4 prior to sacrifice. Tissue prepared from P4-injected rats as well as those from rats not receiving P4 but incubated with ionophore A-23187, generated and released significantly more PGF2 alpha into the incubating solution than basal controls, but failed to exhibit changes in the basal output of PGE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of luteinizing hormone on superovulatory and steroidogenic responses of rat ovaries to infusion with follicle-stimulating hormone

Immature female rats were infused s.c. continuously over a 60-h period with a partially purified porcine pituitary follicle-stimulating hormone (FSH) preparation having FSH activity 4.2 x NIH-FSH-S1 and luteinizing hormone (LH) activity 0.022 x NIH-LH-S1. High rates of superovulation were observed in rats receiving 1 U FSH/day, with 69 +/- 11 oocytes/rat recovered as cumulus-enclosed oocytes from oviducts on Day 1 (equivalent to the day of estrus). Addition of LH to the FSH, at dosages equivalent to 2.5-100 micrograms/day NIH-LH-S1 equivalents (2.5-100 mU) resulted in a dose-related inhibition of superovulation, reaching a nadir of 15 +/- 7 oocytes recovered from rats receiving 50 mU LH/day together with 1 U FSH/day. At the two highest LH doses, 50 and 100 mU/day, ovulation was advanced so that 12 +/- 3 and 15 +/- 4 oocytes, respectively, were recovered from oviducts of these rats flushed on the morning of Day 0, compared to none in rats infused with FSH alone. Ovarian steroid concentrations (ng/mg) observed on the morning of Day 0 in rats infused with FSH alone were progesterone, 0.50 +/- 0.13; testosterone, 0.16 +/- 0.08; androstenedione, 0.06; and estradiol, 0.23 +/- 0.05. On the morning of Day 1, ovarian progesterone concentrations in rats infused with FSH alone had risen to 3.30 +/- 0.33 ng/mg, whereas concentrations of testosterone, androstenedione, and estradiol, had fallen to essentially undetectable levels. Addition of LH to the FSH infusion resulted in dose-related increases, on Day 0, of all four steroids up to a dosage of 25 mU LH/day. At higher LH dosages, Day 0 ovarian concentrations of androgens and estradiol fell markedly, while progesterone concentrations continued to increase. Histological examination of ovaries revealed increases in the extent of luteinization of granulosa cells in follicles with retained oocytes on both Days 0 and 1 in rats infused with 25 and 50 mU LH/day together with 1 U FSH/day, compared to those observed in rats receiving FSH alone. These findings indicate that the elevated progesterone levels on Day 0 and inhibition of ovulation observed at these LH doses were due to premature luteinization of follicles, thus preventing ovulation. At lower LH doses, no sign (based on histologic or steroidogenic criteria) of premature luteinization was evident, suggesting that the decreased superovulation in these rats was due to decreased follicular maturation and/or increased atresia rather than to luteinization of follicles without ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Action of prostaglandin F2α on pregnancy in hamsters: Luteolytic and extra-ovarian effects

Pregnancies in hamsters may be terminated with 10 μg PGF_2α administered b.i.d. on days 4, 5 and 6 of gestation. Small (250 μg and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 μg of estrone essentially normalized the gestation; administration of PGF_2α at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F_2α on pregnancy in hamsters.     

Prostaglandin F2 alpha-stimulated release of ovarian oxytocin in the sheep in vivo: threshold and dose dependency

To determine the threshold of prostaglandin F2 alpha (PGF2 alpha)-stimulated oxytocin secretion from the ovine corpus luteum, low levels of PGF2 alpha (5-100 pg/min) were infused into the ovarian arterial blood supply of sheep with ovarian autotransplants. PGF2 alpha was infused for six sequential 10-min periods at hourly intervals, 6, 12, or 24 days after estrus (n = 3 for each day). Each cycle day was studied during a separate cycle. Oxytocin and progesterone in ovarian venous and carotid arterial plasma was measured by radioimmunoassay, and secretion rates were determined (venous-arterial concentration x plasma flow). In animals treated on Day 6, 5 pg/min PGF2 alpha caused a significant release of oxytocin (p less than 0.01), whereas in animals treated on Day 12, this threshold was 40 pg/min (p less than 0.05). In animals treated on Day 24, the threshold for oxytocin release was greater than 100 pg/min. PGF2 alpha did not significantly change ovarian blood flow or progesterone secretion rate on any day (p greater than 0.05). To determine residual luteal oxytocin after each threshold experiment, 5 mg PGF2 alpha was given i.m. to all animals. Significantly more oxytocin was released by Day 6 than by Day 12 and Day 24 corpora lutea, and by Day 12 than by Day 24 corpora lutea (1.2 micrograms, 0.7 microgram, and 0.3 microgram, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma gonadotropins and prolactin in pseudopregnancy in the rat

Radioimmunoassay presented a method of measuring plasma levels of FSH,LH and prolactin in pseudopregnant rats. Plasma prolactin levels doubled 15 minutes following cervical probing (p .01) on the day of estrus. Plasma LH levels were not significantly elevated. Due to the use of ether anesthesia at blood collecting 3 hr before and 15 minutes after stimulation, only 1 of 16 rats developed pseudopregnancy. On Day 4 of pseudopregnancy in rats mated with vasectomized males; plasma LH was lower (p .05) than in normal rats on the first day of diestrus, perhaps due to the suppressive action of ovarian progesterone and some estrogen. FSH was higher than in normal rats (p .05) perhaps due to the lesser sensitivity of FSH to the inhibitory effect of progesterone. Large decidoumata developed by Day 9 in uterine horns traumatized on Day 4 (153 plus or minus 8 mg uterus weight compared to 1510 plus or minus 204 mg). Thus, the corpora remain functional after LH and prolactin are at normal and subnormal levels. On Day 9 plasma prolactin was lower than at Day 1 of diestrus (p .001). Plasma FSH was elevated (p .01). Plasma LH was unchanged. The degree of rise of LH levels 5 days following ovariectomy on Day 4 of psuedopregnancy or on the first day of diestrus was greater in the former group (p .02), perhaps due to rebound of LH from suppression by ovarian steroids. FSH rose equally in both groups. Prolactin remain about the same. Increased prolactin release by the adenohypophysis was briefer than expected.     

The ovarian-adrenal axis in the guinea pig: effects of photoperiod, cyclic state and ovarian steroids on serum cortisol levels

The effect of photoperiod and reproductive cycle on the fluctuations in basal serum cortisol (F) levels were determined in adult female guinea pigs bled by intracardiac puncture under light methoxyflurane anesthesia. Blood samples were collected at regular intervals over a 24 hour period in order to assess the effects of the lighting regime (14 hr light/day: lights on 0600 hr) on basal levels of F. Peak F levels were observed at the beginning of the light cycle and lowest levels observed just prior to the onset of darkness in random, cyclic female guinea pigs. When analyzed for the influence of reproductive state, basal F levels were found to be elevated during proestrus, Day 2 (Day 0 = estrus) and the mid-luteal (Day 6-7) period of the estrus cycle. In ovariectomized animals a 10 microgram dose of estradiol (E) induced a dramatic rise (P less than 0.001) in adrenal weight and the basal levels of serum F as compared with oil-treated controls. Lower doses of E (1 microgram) and combined progesterone (2 mg)-E (1 microgram) treatment induced an elevation in adrenal weight and/or basal levels of serum F. Progesterone administration alone had no effect on either of these adrenal indices as compared with controls. These data indicate that both photoperiod and ovarian steroid hormone milieu affect adrenal function in the female guinea pig.     

Oxytocin and bovine parturition: a steep rise in endometrial oxytocin receptors precedes onset of labor.

Oxytocin receptors were measured in myometrium and intercaruncular endometrium of cows during pregnancy and parturition. Concentrations of estradiol-17 beta, estrone, and progesterone in peripheral blood were also measured. Receptor concentrations in the endometrium rose almost 200-fold from Day 20 to term (p < 0.0001, ANOVA), from 40 +/- 11 to 7300 +/- 1430 fmol/mg protein. Myometrial receptor concentrations increased 10-fold from 180 +/- 36 fmol/mg on Day 20 to 1850 +/- 360 fmol/mg protein at term (p < 0.0001, ANOVA). During labor, endometrial receptors (6600 +/- 1300 fmol/mg) remained at prelabor values, whereas myometrial receptor concentrations had decreased to 1190 +/- 316 fmol/mg (not significant) and declined further postpartum. Plasma concentrations of progesterone declined from 4-5 ng/ml to about 2 ng/ml between Days 250 and 282 and dropped to < 0.2 ng/ml shortly before delivery. Plasma concentrations of estrone and estradiol-17 beta were below 10-20 pg/ml until Day 230. Estrone concentrations were significantly (p < 0.05) increased by Day 250 and estradiol-17 beta by Day 270, and then both rose rapidly. During labor, plasma estrone was 1135 +/- 245 pg/ml and plasma estradiol-17 beta was 226 +/- 131 pg/ml. The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122). The regulation of oxytocin receptors by ovarian hormones in the two tissues may therefore differ.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of progesterone on the spontaneous motility and prostaglandin synthesis in uterine horns isolated from ovariectomized rats

The motility of isolated uterine horns as well as the generation of PGE and PGF-like material by uterus from spayed rats, treated or untreated with progesterone or progesterone plus estradiol-17-beta, were studied. The changes of Functional Activity (FA) with time (constancy) of control uterine horns and that preparations treated wtih 2 mg of progesterone (P) were not significantly different. However, the PGF-like material released into the bathing solution was significantly higher when the animals were treated with P. PGE-like material in the medium was similar in both groups. With higher doses to P (4 mg/day/2 days) the constancy of FA was similar to that observed in untreated animals, and the PGF-like material released into the medium was significantly higher than in the control group FA and PGs releases into the bathing medium by uterine horns from supra-renalectomized-ovariectomized animals (treated or not with P) were similar to those obtained in spayed rats with the intact suprarenal gland, but the absolute values of PGF-like material were always lower than in this group. Estradiol-17-beta injected prior or after P diminished the stimulation induced by P on the release of PGF-like material into the medium. The constancy of the contractile activity as well as the uterine release of PGE-like material was also diminished in rats treated with P plus estradiol-17-beta. The novel finding that progesterone stimulates the synthesis of PGF in uterine horns from ovariectomized rats without changing that of PGE is discussed.     

A Novel Sesquiterpene,Tuberonone, from Solanum tuberosum L.

The effects of the ovarian hormones progesterone and estrone on the conversion of tryptophan to nicotinamide in rats were investigated. Female rats were fed for 35 days with a 20% casein diet, or with a 20% casein diet containing 0.1% progesterone, or 0.001% estrone, or 0.1% progestrone and 0.001% estrone. The conversion ratio of tryptophan to nicotinamide on the last day of the experiment was 2% in the groups fed with the 20% casein diet and the diet containing 0.1% progesterone, but around 1.2% in the group fed with 0.001% estrone, and 0.7% in the group fed with 0.1% progesterone and 0.001% estrone. These results demonstrated that administration of ovarian hormones significantly decreased the conversion of tryptophan to nicotinamide.     

Plasma progesterone concentrations derived from the administration of exogenous progesterone to ovariectomized mares.

Six ovariectomized mares were divided into 3 groups to determine the effects of exogenous progesterone in oil and repositol progesterone on plasma progesterone concentrations. Progesterone in oil was administered in 7 daily injections in Exp. I. Progesterone concentrations were not maintained greater than 1.0 ng/ml for 24 h with 50 mg/day. However, they remained greater than 1.0 ng/ml during the last 4 days of 100 mg/day and greater than 1.5 ng/ml throughout the injection sequence of 200 mg/day. Repositol progesterone was administered on Days 1 and 7 in Exp. II. At 500 mg, progesterone concentrations peaked in 6 h but returned to near 1.0 ng/ml in 2 days. At 1000 mg and 2000 mg, plasma progesterone was maintained at approximately 2.0 and 4.0 ng/ml respectively for 7 days after injection on Day 1 and was 1.5 and 3.5 ng/ml respectively, 11 days after injection on Day 7. An indication of a cumulative effect on plasma progesterone was observed following repeated dosages of both progesterone in oil and repositol progesterone.     

Ovarian steroid production in vitro during gonadal regression in the turkey. I. Changes associated with incubation behavior.

The mechanism regulating ovarian regression during incubation behavior in the domestic turkey has not been elucidated. This study was designed to determine whether ovarian steroidogenic potential is depressed during gonadal regression associated with the onset of incubation behavior. Hens were housed in floor pens equipped with trap nests that were checked 7 times per day. Hens were grouped, according to nesting frequency and egg production, into the following classifications: laying (laid an egg every day and trapped in the nest only once/day); transitional (laid an egg every day but trapped in the nest 4 or more times/day); and Day 1, Day 3, and Day 5 incubating (no egg for 2, 4, or 6 days, respectively, while trapped in the nest at least 4 times/day). Follicular atresia was evident in the largest preovulatory follicle (F1) in transitional hens, extensive in F1 through the third largest follicle (F3) in Day 1 incubating hens, and extensive in F1 through F7in Day 3 incubating hens. Levels of circulating LH, progesterone (P), androgen (A), and estradiol (E) decreased in transitional hens relative to concentrations in laying hens and remained low thereafter. In contrast, levels of prolactin were greater in Day 3 and Day 5 incubating hens than in laying, transitional, or Day 1 incubating hens. Basal production of P by F1 granulosa cells was lower from Day 1 incubating hens than from the other groups. Production of P in response to porcine-luteinizing hormone (pLH) was greater by cells from transitional and Day 1 incubating hens than from those of laying hens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of blastocysts on rat ovarian steroidogenesis in early pregnancy.

The biosynthesis of ovarian progesterone and 20alpha-hydroxypregn-4-en-3-one (20alpha-OHP) was studied in rats with pituitaries autotransplanted beneath the kidney capsule (APTr rats) 1 1/2 days after ovulation. Some animals underwent tubal ligation 1-2 weeks prior to mating. Incubated ovarian tissue slices showed an accumulation of progesterone of 64 plus or minus 11 mcg/g tissue, and a progesterone/20alpha-OHP ratio of .32 plus or minus .16. Ovarian tissue from APTr rats with viable blastocysts synthesized considerably more progesterone than tissue from tubal ligated APTr rats. The increased concentrations of progesterone were associated with decreased concentrations of 20alpha-OHP. The accumulation of progesterone in tissue from unmated APTr rats, APTr rats cervically stimulated at proestrus, and similar cervically stimulated rats with traumatized uteri was 42 plus or minus 5, 16 plus or minus 4 and 18 plus or minus 9 net mcg/g tissue, respectively. The progesterone accumulation in tissue from cervically stimulated rats was thus similar to that in tissue from tubal ligated animals. This inhibition by cervical stimulation was overcome by stimuli from the blastocysts. The results suggest that the blastocyst secretes a substance that is more active in promoting progesterone formation than pituitary prolactin.     

Postcopulatory effects of two antifertility agents on ova transport and implantation

The daily doses which prevented implantation in 50 percent of treated animals (ED50) of 2,3 - bis (4-hydroxyphenol) valeronitrile (SC-3402) and 2,3 - bis (4-methoxyphenyl) pent-2-enenitrile (SC-3296) injected in rats s on Days 1 to 3, or Days 4 to 7, or Days 1 to 7 (Day 1 = pregnancy) were 100, 200, and 40 mcg and 50, 100, and 12 mcg respectively, ED50 doses of estrone were 4,8 and 3.5 mcg. Control animals showed ova in the oviduct only on Days 1, 2 and 3, also in the uterus on Day 4, and only in the uterus on Day 5. Very few ova were found in rats treated with 10 mcg estrone daily Day 1-2 and autopsied on Day 3. The same treatment period with 200 mcg SC-3402 caused similar results. 64 mcg SC-3402 resulted in a smaller reduction of ova. Acceleratory potency of 200 mcg SC-3402 is greater than can be due to its estrogenic activity equivalent, 0.5 mcg estrone; that of 64 mcg SC-3296 (4.8 equivalents estrone) can be so ascribed. Rats receiving daily 4-8 mg 17 alpha-acetoxy-6 alpha-methylprogesterone (MAP) from Day 1 to 9 to delay nidation, and 200 mcg SC-3402, autopsied on Day 10 showed no free blastocysts and a few implantation sites in the process of resorption (Free blastocysts were found in rats similarly treated but with ligation of the uterus at the cervix on Day 5 to prevent expulsion of blastocysts). Control rats on Day 10 showed a few implantation sites and free blastocysts. The normal number of implantations were present in SC-3296 treated rats. The average weight of cornu traumatized by threading one cornu in psuedopregnant rats with a silk thread on Day 5 (Day 1=cervical stimulus) in rats treated with 200 mcg SC-3402 on Days 5-8, 404 plus or minus 50 mg was significantly (P less than .05) lower than mean control weight, 794 plus or minus 48 mg. The difference between the mean weight of non-traumatized cornu of rats given 100 mcg, 284 plus or minus 36 and 232 plus or minus 12 mg respectively was significantly (P less than .05) greater than in controls, 159 plus or minus 5.8 mg. The deciduoma-inhibiting activity of SC-3402 is further evidence that it initiates nidation but impedes early implantation stages.     

Ovarian steroid production in rats treated with gonadotropin-releasing hormone during early pregnancy

In the pregnant rat, luteinizing hormone (LH) stimulates the ovarian production of testosterone (T) which is aromatized to estradiol (E2). E2 promotes progesterone (P) synthesis by the ovary. To determine if the administration of gonadotropin-releasing hormone (GnRH) disrupts pregnancy by suppressing ovarian steroid production, rats were treated on days 7-12 of pregnancy with 25, 50 or 100 micrograms/day of GnRH or 0.2, 1 or 5 micrograms/day of a GnRH agonist (GnRH-Ag). The higher two doses of GnRH or GnRH-Ag within 24 h suppressed peripheral levels of plasma P and terminated pregnancy within 48 h. By day 12, P levels in the ovarian vein in rats treated with GnRH or GnRH-Ag in respective doses were 2098 +/- 261, 732 +/- 437, 110 +/- 15, and 2575 +/- 463, 49 +/- 9, 43 +/- 8 compared to 1833 +/- 433 ng/ml in controls. Daily treatment of P (4 mg) and E2 (0.5 microgram) simultaneously with GnRH-Ag at its maximum dose reversed the abortifacient effect of GnRH-Ag and maintained pregnancy. Peripheral levels of Plasma LH in all groups were higher than controls on days 10 and 12. Ovarian vein levels of T on days 10 or 12 of pregnancy were either not significantly different from controls (at 2703 +/- 607 or 3249 +/- 690 pg/ml, respectively) or increased dramatically to 9547 +/- 1769 on day 10 and to 5985 +/- 1426 pg/ml on day 12 in rats treated with 0.2 microgram of GnRH-Ag. Similarly, ovarian vein levels of E2 on days 10 or 12 were either not significantly different from controls (at 2022 +/- 227 or 2793 +/- 184 pg/ml, respectively) or increased dramatically to 2980 +/- 58 pg/ml on day 10 in rats treated with 25 micrograms of GnRH or to 3296 +/- 241 on day 10 and to 3420 +/- 325 pg/ml on day 12 in rats treated with 0.2 microgram of GnRH-Ag. These results indicate that the abortifacient effect of GnRH administration in rats is not due to its effect on the uterus, but to its suppressive effects on ovarian P secretion. There was no evidence to show that a GnRH-induced fall in ovarian secretion of either T or E2 were involved in this process.     

Effects of hormonal manipulation on the resumption of postpartum reproductive activity in Texel ewes

Three experiments were conducted on Texel ewes to study the influence of prostaglandin F(2alpha) (PGF(2alpha)), prolactin (PRL), estradiol (E(2)), and gonadotrophin releasing hormone (GnRH) on postpartum reproductive activity. In Experiment 1, oral administration of indomethacin (25 to 50 mg/day/ewe) from Day 3 post partum to the first detected estrus inhibited plasma 13, 14-dihydro-15-keto, PGF(2alpha) (PGFM) concentrations (P < 0.0001). This treatment resulted in an earlier rise in the frequency and amplitude of luteinizing hormone (LH) pulses and a resumption of estrous behavior (P < 0.05), while ovarian activity estimated by progesterone (P(4)) concentrations resumed to the same extent in treated ewes and controls. Bromocriptine treatment (2.5 mg/day/ewe) reduced plasma PRL levels (P < 0.0001) but had no effect on ovarian activity as evidenced by P(4) and resumption of estrus or on either the frequency or amplitude of the LH pulse. In Experiment 2, a single injection of GnRH agonist (42 mcg of buserelin/ewe) on Day 16 post partum resulted in an abrupt elevation of plasma LH concentrations; mean LH values were 18 to 27 times higher when compared with those of the control ewes. Two days after this treatment, ovulations occurred in 5 of the treated ewes and in 2 of the control ewes. This induced ovarian activity was not associated with estrous behavior; however, after an adequate subsequent luteal phase all the treated ewes displayed estrus, the resumption of estrus thus being earlier in treated than in control ewes (P < 0.01). In Experiment 3, E(2) supplementation from Day 16 to Day 28 post partum increased the number of LH pulses per 6 hours in suckling ewes (P < 0.05) and induced earlier resumption of estrus in dry ewes but not in suckling ewes (P < 0.01). Luteal function was detected about 5 and 8 days after the insertion of E(2) implants in 4 dry ewes and in 2 suckling ewes, respectively.