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PubMed1983

Evaluation of clinical and luteolytic effects of a novel prostaglandin analogue in normal and problem mares.

Alfaprostal (K 11941), a novel prostaglandin F2 alpha analogue was clinically tested in 24 dioestrous mares, 40 anoestrous mares and 31 postpartum mares, all being given 2 or 3 mg intramuscularly. Blood samples were taken for the determination of plasma progesterone levels and the objective confirmation of luteolytic drug effects. Two hundred and thirty-six mares at the same location were used for comparisons of the rates of pregnancy, early embryonic loss and foaling. Alfaprostol was found to act as a potent luteolytic agent with good oestrus induction, follicular development and normal conception (72.6%) and foaling rate (65.3%). No side effects were observed. Treatments commenced early in the season (October), when only 35% of the anoestrous mares showed elevated progesterone levels, but in 80% of anoestrous mares with baseline progesterone levels, alfaprostol initiated heat and ovulation followed by normal fertility.

Animals↗
PubMed1995

Luteotropic and luteolytic effects of oxytocin in the porcine corpus luteum.

The presence and the release of oxytocin (OT) by corpora lutea (CL) of a number of species (Wathes et al. 1986, Watkins and Choy 1988) including ruminants (Ivell and Richter 1984, Hirst et al. 1986, Rodgers et al. 1983, Sawyer et al. 1986), primates (Dawood and Khan-Dawood 1986, Khan-Dawood 1987, Maas et al. 1992, Khan-Dawood et al. 1993), and the pig (Pitzel et al. 1984, Einspanier et al. 1991, Jarry et al. 1992) have been amply verified. Conflicting results concerning the effects of OT on steroidogenesis have been published; the peptide has been shown to be luteotrophic (Sawyer et al. 1986, Maas et al. 1992, Jarry et al. 1990), to have no effects (Rodgers et al. 1985) or to be luteolytic (Auletta et al. 1984, Auletta et al. 1988, Pitzel et al. 1988) and it appears that this confusion is only in part due to species differences but also the age of the luteal tissue seems to be of crucial importance for the understanding of the effects of OT (Schams et al. 1983, Wuttke et al. 1993, 1994). In the present contribution we will focus largely on our results obtained in the pig and where applicable, compare them with those obtained in other species. We will thus demonstrate that OT is released by luteal cells (Jarry et al. 1990, Einspanier et al. 1991, Jarry et al. 1992) and that luteal cells have OT receptors (Sernia et al. 1989, Pitzel et al. 1993a) which mediate the effects of the peptide on steroidogenesis. Finally, we will address the question whether OT is inhibitory or stimulatory to progesterone (P) and estradiol (E2) release, and we will come to the conclusion that OT is both luteotropic and luteolytic (Wuttke et al. 1993, 1994). The CL of all species investigated so far consists of two steroidogenic cell types. The so-called large luteal cells stem from follicular granulosa cells and they appear to be barely responsive to luteinizing hormone (LH)/human chorionic gonadotrophin (hCG) but they are highly receptive to prostaglandin F2 alpha (PGF2 alpha) (Hansel and Dowd 1986, Pitzel et al. 1990). Furthermore, they appear to produce OT (Rodgers et al. 1983, Theodosis et al. 1986). The small luteal cells are believed to derive from the follicular theca cells (Hansel and Dowd 1986, Pitzel et al. 1990). They are LH-receptive but synthesize few, if any, regulatory peptides. In the last few years it has become increasingly evident that cells deriving from the white blood cell line are involved in processes such as ovulation and luteolysis. Of crucial importance for the understanding of luteolysis is the morphological observation that macrophages invade the CL at the time of luteal regression (Adashi 1990, Paavola 1977, Kirsch et al. 1981).

Animals↗
PubMed1975

Assessment of possible luteolytic effect on intra-ovarian injection of prostaglandin F-2ALPHA in the human.

A group of five patients awaiting laparoscopic tubal diathermy were followed by daily assay of luteinising hormone (LH) and progesterone. Between five and eight days after the LH peak, prostaglandin F-2ALPHA (PGF-2ALPHA) was injected into either the corpus luteum or the ovarian stroma. Doses of 100 mu-g into the corpus tuteum, 1000 mu-g into the adjacent stroma and 500 mu-g into an indeterminate ovarian structure had no effect on peripheral plasma progesterone levels or uterine bleeding. An injection of 500 mu-g or 1000 mu-g given unequivocally into the corpus luteum produced a rapid and profound fall in plasma progesterone levels, the nadir coinciding with the onset of uterine bleeding which commenced 24 hours after the injection and persisted for more than seven days. Injection of 100 mu-g in the same volume of saline had no such effect. Despite continued bleeding plasma progesterone levels returned to normal luteal levels for three days and then fell again.

Corpus Luteum↗
PubMed1994

Luteolytic effect of prostaglandin F2 alpha and two metabolites in ewes.

Twenty-three ewes were used in an experiment to determine the point in metabolism at which prostaglandin (PG) F2 alpha loses its luteolytic activity. Ewes exhibited at least one normal estrous cycle (15 to 19 d) and then were randomly assigned to one of four treatment groups: 1) control, 2) PGF2 alpha, 3) 15-keto-PGF2 alpha, or 4) 13,14-dihydro-15-keto-PGF2 alpha (PGFM). Each ewe received an i.m. injection of the designated treatment (5 mg in 1 mL of sterile saline) during the midluteal phase of the estrous cycle (d 8, 9, 10, or 11 after estrus). An identical second injection was given to each ewe 3 h after the first injection. Beginning at 9 h after injection, concentrations of progesterone were lower (P < .01) in the PGF2 alpha-treated ewes than in ewes in the other three groups. These differences were maintained throughout the duration of the 48-h sampling period in five of the six ewes that received PGF2 alpha. None of the ewes in the other three treatment groups exhibited any change in concentrations of progesterone. Ewes were classified as completing luteolysis if concentrations of progesterone decreased to less than 1 ng/mL within 48 h after the first injection. Five of the six ewes receiving PGF2 alpha completed luteolysis (P < .05), whereas none of the ewes in the other three groups completed luteolysis. The interestrous interval was reduced by approximately 5 d in the PGF2 alpha-treated group compared with the other three treatment groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Comparison of luteolytic effectiveness of several prostaglandin analogs in heifers and relative binding affinity for bovine luteal prostaglandin binding sites.

The relative binding affinities for both the prostaglandin (PG)E1 and PGF2alpha specific bovine luteal binding sites were determined for five PGE and fourteen PGF derivatives and analogs. Relative binding affinity was determined in vitro using membranes prepared from bovine corpora luteal (CL) obtained from the slaughterhouse. The parent structure of the analog was a dominant feature in determining the affinity for the respective PG binding site. Luteolysis was determined in cattle following intramuscular injection of various doses of prostaglandin once between days 6 and 14 after estrus and measuring CL regression by ovarian palpation per rectum, interval between injection and return to estrus and duration of the subsequent estrous cycle. A dose which was luteolytic was established for each of eight PGF-type compounds, and a dose which was not luteolytic was also established. There appeared to be limited association between the relative affinity for the PGF2alpha specific site in vitro and the estimated luteolytic dose range of these PGF analogs when tested in cattle. Differences in in vivo luteolytic potency for the compounds tested could not be explained by differences in binding affinity. Differences in metabolism and absorption may also be important in the determination of in vivo potency.

Animals↗
PubMed1983

Luteolytic effect of 13,14-dihydro-PGF-2 alpha in heifers.

Holstein heifers (4/group) were injected intramuscularly with 0, 5, 10 or 25 mg 13,14-dihydro-PGF-2 alpha on Day 10 of the oestrous cycle. Complete luteolysis and precocious oestrus occurred in 3 of 4 heifers receiving 25 mg and 1 of 4 receiving 10 mg 13,14-dihydro-PGF-2 alpha injected i.m. These features were not affected in heifers injected with 0 or 5 mg 13,14-dihydro-PGF-2 alpha, although plasma progesterone concentrations were depressed in all treated heifers within 75 min. LH concentrations were elevated between 5 and 8 h after 13,14-dihydro-PGF-2 alpha in all treated heifers. The addition of 13,14-dihydro-PGF-2 alpha to dispersed bovine luteal cells did not affect progesterone accumulation during a 2-h period. These results suggest that 13,14-dihydro-PGF-2 alpha may play a role in PGF-2 alpha-induced luteolysis.

Animals↗
PubMed1983

The importance of a luteolytic effect of the pituitary in understanding the placental control of the rat corpus luteum.

In rats bearing a full complement of conceptuses (FC-bearing rats) progesterone secretion increases about 1.5 times and the corpora lutea double in weight between days 12 and 16. Reducing the number of conceptuses to one (by aspirating all but the single conceptus) at any time between days 7 and 12 of pregnancy (day 1 = insemination) caused progesterone secretion and corpus luteum weight to remain at or below the day 12 level until term. When rats bearing one conceptus were hypophysectomized on day 12, however, serum progesterone increased and fell after day 12 in a pattern almost identical to that in FC-bearing rats, except that the peak and trough occurred about 2 days later; hypophysectomy on day 15 or 18 also increased serum progesterone to values approaching those in intact FC-bearing rats. In a series of rats bearing experimentally determined conceptus numbers between 0 and 5 or naturally occurring ones of 6-16, the serum level of placental lactogen on day 12 (the day of the first peak of secretion of this hormone) was directly proportional to conceptus number over the entire range. The pattern of rat placental lactogen secretion between days 7 and 23 in FC-bearing rats included two peaks, on day 12 and on days 18-21, but in one-conceptus-bearing rats, the level was only slightly higher than the PRL level, and it remained unchanged, even by hypophysectomy, until term. Serum PRL levels bore no relation to conceptus number, were very low, and were unaffected by hypophysectomy except in the FC-bearing rats, in which lypophysectomy prevented the rise that normally occurs after day 21. These results, especially in relation to others previously reported, show that by day 12 of pregnancy, the rat pituitary, instead of merely becoming luteotropically inactive, produces a substance that inhibits further development of the corpora lutea. The results also imply that the placentas maintain luteal growth and progesterone secretion as much by suppressing this luteolytic activity as by stimulating the corpus luteum directly.

Animals↗
PubMed1991

Local luteolytic effect of prostaglandin F2 alpha in the human corpus luteum.

OBJECTIVE: To evaluate the effects of prostaglandin (PG)F2 alpha on human corpus luteum (CL) function in vivo. DESIGN: The effects of a single injection of PGF2 alpha into the CL was studied. SETTING: The patients underwent elective surgery at the Department of Obstetrics and Gynecology, Sahlgrenska Hospital, University of Göteborg, Sweden. PARTICIPANTS: Twenty women with regular menstrual cycles undergoing laparoscopy for legal sterilization with tubal clips volunteered for the study. INTERVENTIONS: Prostaglandin F2 alpha (3 mg) was injected through the abdominal wall into the CL. In control cases, vehicle was injected into the CL or PGF2 alpha into the contralateral ovary. MAIN OUTCOME MEASURE: After the injections, serum was analyzed for progesterone (P) and luteinizing hormone using fluoroimmunoassay and enzyme-immunoassay, respectively. Menstrual data were recorded. RESULTS: In contrast to control cases, intraluteal injection of PGF2 alpha caused both an immediate fall of greater than 30% in serum P and a shortening of the luteal phase by 2 to 5 days. Luteinizing hormone varied independently of the changes in serum P levels. CONCLUSION: The results suggest a local role for PGF2 alpha in human luteolysis.

Adult↗
PubMed1975

Prostaglandin E1 and F2alpha specific binding in bovine corpora lutea: comparison with luteolytic effects.

Preliminary characterization indicated the presence of separate prostaglandin (PG)E1 and (PG)F2alpha 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 x 10(-9)M and 1.1 x 10(-8)M for PGE1 and PGF2alpha, respectively. Competition of several natural prostaglandins for the PGE1 and PGF2alpha bovine luteal specific binding sites indicates specificity for the 9-keto or 9alpha-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 PGF2alpha as measured by reduced estrous cycle length, decreased corpus luteum size and significantly decreased plasma progesterone levels. In contract, treatment with 25 mg PGE1 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 PGE1 treatment compared to pretreatment values. In so far as data obtained in vitro on PGF2alpha relative binding affinity to the bovine CL can be compared to data obtained independently in vitro on PGF2alpha induced luteolysis in the bovine, PGF2alpha relative binding to the CL and luteolysis appeared to be associated. By similar reasoning, there was no apparent relationship between PGE1 relative binding affinity in the luteal fractions and luteolysis in estrous cyclic cattle.

Animals↗