Prostaglandin F2alpha (PGF2alpha) and prolactin secretion in rats.

Plasma prolactin and F-prostaglandins (PGF) were measured anesthetized male Sprague-Dawley rats before and at 15, 30, 45 and 60 minutes following i.v. injection of either PGF2alpha (4 mg/kg), chlorpromazine, 1 mg/kg or chlorpormazine (1 mg/kg) after pretreatment with i.p. indomethacin (2 mg/kg). Following PGF2alpha administration, plasma prolactin levels increased significantly only at 15 and 30 minutes in spite of extremely high PGF levels throughout 60 minutes. Besides the expected rise in plasma prolactin, chlorpromazine caused a transient but statistically significant increase in PGF. Indomethacin blocked the chlorpormazine-induced PGF rise but not prolactin increase. Animals stressed with ether anesthesia showed elevation of plasma prolactin, which was not blocked by indomethacin although PGF concentration fell. Theese results indicate that PGF2alpha can stimulate prolactin release. This effect does not appear to be physiologic since very high PGF levels are required. Furthermore, blockade of prostaglandin synthesis by indomethacin does not prevent the release of prolactin in response to chlorpormazine or stress. Our findings do not support a possible role of PGFs as intermediaries in prolactin release. However, it is possible that PGFs may work through other mechanisms not investigated in our study.     

Prostaglandin F2alpha specific binding in equine corpora lutea

Preliminary studies indicate the presence of PGF2alpha specific binding sites in membrane fractions prepared from equine corpora lutea. The equilibrium binding data indicate an apparent dissociation constant of 3.2 X 10(-9)M and the concentration of binding sites of -0.1 pmoles/mg membrane protein. Competition of several natural prostaglandins for equine luteal PGF2alpha specific binding sites indicates specificity for the 9alpha-hydroxyl moiety and the 5,6-cis doublebond. Significant increases in relative binding affinities were demonstrated for PGF2alpha analogs with a phenyl ring introduced at carbons 16 or 17. Specific PGF2alpha binding was demonstrated in corpora lutea collected at known stages of the estrous cycle. There was no pattern in these values based on the stage of the cycle. While specific 3H-PGE1 binding could be demonstrated, no high affinity sites could be quantitated. 3H-PGE1 binding appeared unaffected by changes in temperature or time of incubation, whereas PGF2alpha specific binding was significantly modified by both these factors.     

Prostaglandin F2 alpha and oxytocin interactions in ovarian and uterine function

The oxytocin-neurophysin gene is expressed in several nontraditional sites within the endocrine system. In the ovary its expression in the corpora lutea is initiated by ovulation. Ovarian oxytocin concentrations reach maximal levels around day 11 of luteal cycle and fall to a nadir at estrus. PGF2 alpha has the capacity to release oxytocin from the corpus luteum, and oxytocin in turn releases PGF2 alpha from the uterine endometrium or decidua. This positive feedback loop between the ovary and the uterus ensures the completion of luteolysis in species that depend on the presence of the uterus for the termination of luteal lifespan. Immunization against oxytocin has been shown to disrupt this loop, resulting in much-prolonged luteal cycles. In primates and other species in which luteal life span is independent of the uterus, an oxytocin PGF2 alpha interaction may take place within the ovary itself. At parturition a related interaction takes place which ensures the expulsion of the fetus and placenta in an orderly manner. Oxytocin of both pituitary and ovarian origin reaches the uterus via its blood supply and binds to two types of receptors: one on myometrial cells, the occupation of which initiates contractions, and the other on decidual cells, the occupation of which initiates prostaglandin generation. This prostaglandin diffuses into the adjacent myometrium and augments the oxytocin-induced contractions. In conjunction with a direct softening effect by prostaglandins on the cervix the augmented contractions achieve the force needed to dilate the cervix and expel the fetus. An additional source of oxytocin during labor may be the placenta, another non-traditional site for the occurrence of oxytocin.     

Prostaglandin E1 inhibits the pulmonary vascular pressor response to hypoxia and prostaglandin F2alpha.

In the anesthetised dog an infusion of exogenous prostaglandin E1 (100muG/min) inhibits the pulmonary vascular pressor response to hypoxia. Both 25 and 100muG/min PGE1 can reduce the transient pulmonary hypertension caused by a bolus of prostaglandin F2alpha. This suggests that hypoxia and PGF2alpha may share a final common pathway in producing pulmonary vasoconstriction. These results may help to explain the mechanism by which endotoxin inhibits the pulmonary vascular response to hypoxia. This effect is probably achieved by stimulating the production of an endogenous dilator prostaglandin. Exogenous PGE1 can mimic this effect.     

Prostaglandin F2 alpha increases responsiveness of pulmonary airways in dogs

We studied the effect of prostaglandin F2 alpha (PGF2 alpha) on the responsiveness of pulmonary airways in dogs. Airway responsiveness was assessed by determining the bronchoconstrictor response to increasing concentrations of acetylcholine aerosol delivered to the airways. In each of five dogs, we determined responsiveness during treatment with physiologic saline, histamine, or PGF2 alpha aerosols. The doses of histamine and PGF2 alpha were determined by establishing the largest dose of each which could be given to the dog without causing bronchoconstriction (subthreshold doses). We found that airway responsiveness was not significantly different during histamine treatment than after saline, however, responsiveness increased during treatment with PGF2 alpha. In addition, the hyperresponsiveness induced by PGF2 alpha was prevented by pretreatment with the ganglion blocking drug hexamethonium (5 mg/kg given intravenously). The results show that PGF2 alpha specifically increases the responsiveness of pulmonary airways in doses that do not cause bronchoconstriction, and suggest that the hyperresponsiveness involves a neural mechanism such as increased responsiveness of airway sensory nerves.     

Prostaglandin F2alpha and human prostatic affinity for testosterone.

Earlier work had shown that the lactogen, LTH and HPL, foster testosterone binding by the prostate. This study was undertaken to see if prostaglandin F2alpha would oppose the effect of the lactogen on the prostate as it does the luteotrophic action of the hormone on the corpus luteum. When it was found instead that the PGF increases steroid binding and that its interaction with lactogen was neither antagonistic nor additive, attention was directed to further characterization of prostaglandin's effect. A dosage/response study of F2alpha alone showed that concentrations of 4 ng/ml and 40 ng/ml increased binding but that 400 ng/ml did not. Glands with stromal hyperplasia and/or inflammation were not responsive than those with epithelial hyperplasia. Assays of water extracts of the tissue revealed concentrations of about 340 ng of F2alpha per gram fresh weight and that the concentration varied inversely as the beta-glucuronidase activity. If the enzyme level is considered an index of the epithelial cell density within the specimen, the inverse relationship suggest a non-epithelial (stromal) site of prostaglandin concentration.     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

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.     

Prostaglandin E and F2alpha receptors in bovine corpus luteum plasma membranes are two different macromolecular entities.

Greater numbers of prostaglandin (PG) F_2α as compared to PGE receptors were solubilized from bovine corpus luteum plasma membranes by sodium deoxycholate (SDC) concentrations from 0.01% to 0.1%. However, at 0.5% SDC concentration, virtually 100% of both PGs receptors were solubilized. When these solubilized PGs receptors were chromatographed on a calibrated Sepharose 6B column, they exhibited a small but reproducible difference in their distribution coefficients. The above results suggest that PGE and PGF_2α receptors represent two different macromolecular entities with a relatively small size difference between them.     

Prostaglandin E2 localization in the rat ileum.

Summary The application of anti-prostaglandin E₂ immunoglobulin to plastic-embedded thin sections of the rat ileum has permitted the localization of prostaglandin E₂ in this tissue. In agreement with the published data (Chock & Schmauder-Chock (1988), Schmauder-Chock & Chock (1989)), the results also suggest the presence of an arachidonic acid cascade in the granules of various secretory cells of the gut. Since antibody labelling was found within the secretory granules of connective tissue mast cells, goblet cells, and Paneth cells, the presence of the arachidonic acid cascade in these granules is implied. The appearance of prostaglandin E₂ over the non-cellular internal elastic lamina of arterioles suggests that it may have been secreted along with the elastin. The even distribution of prostaglandin throughout the cytoplasm of the erythrocyte is consistent with the concept that this cell scavenges the eicosanoid from the circulation. These data further link the secretorh granule to the production of eicosanoids and therefore illustrate the potential sources of prostaglandins in the rat ileum.