Prostaglandin-mediated stimulation of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release in dispersed human parathyroid cells

Freshly dispersed cells were employed to study the effects of various prostaglandins (PGs) on cAMP accumulation and parathyroid hormone release in abnormal human parathyroid tissue. PGE1 and PGE2 effected dramatic increases in intracellular cAMP accumulation over a concentration range of 10(-6)-10(-4) M; the relative effectiveness of these agents varied among different preparations. PGF2 alpha caused a smaller stimulation of cAMP accumulation, and PGF1 alpha was generally without effect. In contrast with the effect previously described in the bovine parathyroid cell system, PGF2 alpha did not suppress agonist-stimulated cAMP accumulation. Both PGE1 and PGE2 enhanced cellular release of parathyroid hormone, with dose-response characteristics similar to those seen with cAMP. In addition, both agents led to a significant stimulation of adenylate cyclase activity in a cellular homogenate preparation. Neither indomethacin (10(-5) M) nor naproxen (10(-4) M) altered the calcium suppressibility of the cells, suggesting that endogenous PG production does not play a major role in the calcium-mediated regulation of parathyroid hormone release.     

Prostaglandins PGE2 and PGF2 alpha in human fetal lung: immunohistochemistry and release from organ culture.

Immunohistochemical studies in human fetal lung have shown that epithelial and endothelial cells are both strongly and equally reactive for PGE2. In contrast, epithelial PGF2 alpha reactivity varied between fetuses, in some as intense as endothelial staining and in others very much less. As lung organ cultures differentiated, the intensity of PGE2 staining declined in airways and blood vessels, although it was still weakly positive at 10 days. In contrast, epithelial cells rapidly became negative for PGF2 alpha, whereas PGF2 alpha positivity was retained in blood vessels, albeit less obviously. PGF2 alpha and PGE2 were released into the media of organ cultures in decreasing amounts as cultures progressed. Amounts of released PGF2 alpha were greater by 2- to 10-fold than PGE2. Our findings suggest that the endogenous production of prostaglandins by human fetal lung in organ culture has a key role in the self-differentiation process that occurs in the absence of sera or added growth factors or hormones.     

Co-operation of progesterone and prostaglandins in ovulation induced by human chorionic gonadotrophin in immature rats primed with pregnant mare serum gonadotrophin

Serial injections of a mixture of prostaglandin (PG) E2 and F2 alpha 0, 2, 4, and 6 h after simultaneous injection of human chorionic gonadotrophin (hCG) and indomethacin incompletely restored the ovulation that would have been blocked by indomethacin in immature rats treated with pregnant mare serum gonadotrophin followed by hCG. Serial injections of another mixture of PGE2 and PGF2 alpha 6, 8, 10 and 12 h after simultaneous injection of hCG and indomethacin similarly reversed, in part, the inhibitory effects of indomethacin on hCG-induced ovulation. In contrast, serial injections of the mixtures of PGE2 and PGF2 alpha 0, 2, 4, 6, 8, 10 and 12 h after simultaneous injection of hCG and indomethacin completely restored the indomethacin-blocked ovulation, suggesting that the prostaglandins mediate the action of hCG on ovulation both in the earlier and later stages of the preovulatory process. Six hours after simultaneous injection of hCG and indomethacin serial injections of a mixture of PGE2 and PGF2 alpha reproduced the acute and temporary increase in concentrations of progesterone and testosterone in plasma which would have been abolished by indomethacin. Progesterone given concurrently with hCG and indomethacin partially antagonized the inhibitory action of indomethacin on ovulation. Serial injections of a mixture of PGE2 and PGF2 alpha 6, 8, 10 and 12 h after concurrent administration of progesterone with hCG and indomethacin completely restored the indomethacin-blocked ovulation, suggesting that progesterone can substitute the action of prostaglandins injected serially in the first half of the preovulatory process. It was concluded that the co-operation of progesterone in the earlier stage and of prostaglandins in the later stage of the preovulatory interval is required to mediate the action of hCG on ovulation.     

Effects of prostaglandin F2 alpha on bone formation and resorption in cultured neonatal mouse calvariae: role of prostaglandin E2 production

Although most studies show that prostaglandin E2 (PGE2) is the most potent and effective of the prostanoids in bone, recent data in cell culture suggest that PGF2 alpha may have unique effects, particularly on cell replication. The present study was undertaken to compare the effects of PGF2 alpha and PGE2 in cultured neonatal mouse parietal bones by simultaneous measurement of bone resorption as release of previously incorporated 45Ca, bone formation as incorporation of [3H]proline into collagenase-digestible (CDP) and noncollagen protein, and DNA synthesis as incorporation of [3H]thymidine. PGF2 alpha was less effective than PGE2 as a stimulator of bone resorption, and its effects were partially inhibited by indomethacin and markedly inhibited by glucocorticoids. In contrast, the resorptive response to PGE2 was unaffected by indomethacin and only partially inhibited by cortisol. PGF2 alpha had little effect on bone formation, in contrast to the biphasic effect of PGE2, which inhibited labeling of CDP in the absence of cortisol and stimulated CDP labeling in the presence of cortisol. PGF2 alpha increased thymidine incorporation into DNA, but the effect was smaller than that of PGE2 and was inhibited by indomethacin. These observations suggested that PGF2 alpha might act in part by stimulating PGE2 production. By RIA, PGE2 concentrations were increased in the medium of bones treated with PGF2 alpha, and this increase was blocked by indomethacin. By HPLC, bones prelabeled with [3H]arachidonic acid showed an increase in labeled PGE2 release, and RIA showed an increase in PGE2 after PGF2 alpha treatment. These results indicate that PGF2 alpha is a relatively weak agonist in bone compared to PGE2 and that some of the effects of PGF2 alpha on bone resorption, formation, and cell replication may be mediated by an increase in endogenous PGE2 production.     

Secretion of progesterone and prostaglandins by cells of bovine corpora lutea from three stages of the luteal phase

The secretion of prostaglandins (PGs) by bovine corpora lutea was investigated. Corpora lutea from the early, early-mid and late-mid stages of the luteal phase were dissociated by collagenase treatment and cultured in monolayer in Dulbecco's modified Eagle's medium containing 10% (v/v) fetal calf serum. Treatment with either LH (100 ng/ml) or dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) had no effect on progesterone secretion by early luteal phase cells but stimulated progesterone secretion two- to fourfold by cells from the latter stages. The secretion rates, per microgram cell protein, of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha were substantially greater in cells from the early luteal phase than in those from the latter stages, however, all changes in PG secretion in response to treatments were qualitatively similar between cells from the three stages of the luteal phase. The secretion rate of 6-keto-PGF1 alpha was greater than that of PGE2 or PGF2 alpha and was inhibited by treatment with indomethacin (28 mumol/l) but unaltered by treatment with LH, dbcAMP or butyrate (1 mmol/l). Secretion of PGE2 was inhibited by indomethacin but stimulated two- to threefold by treatment with either dbcAMP or butyrate. Secretion of PGF2 alpha was minimal and not inhibited further by treatment with indomethacin, but was stimulated 10- to 40-fold with dbcAMP. Indomethacin treatment inhibited the stimulatory effect of dbcAMP; butyrate had no effect on PGF2 alpha secretion. Treatment with LH had no effect on any of the PGs measured. In these experiments the secretion of progesterone appeared unrelated to any changes in the secretion of PGs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholinergic and alpha-adrenergic stimulation of prostaglandin release by dog thyroid in vitro.

Dog thyroid slices released in their incubation medium prostaglandins E2 (PGE2), F2 alpha (PGF2 alpha), 15-keto-13,14-dihydro-F2 alpha, and thromboxane B2 (TxB2), as measured by direct RIA. This release could be inhibited by indomethacin and naproxen, indicating that it corresponded to a neosynthesis. Carbamylcholine (2--100 microns) stimulated the release of PGE2, PGF2 alpha, and TxB2, whereas epinephrine (20 microns to 1 nM) enhanced the release of PGE2 and PGF2 alpha but had no effect on TxB2. These stimulations were inhibited by atropine and dihydroergocryptine, respectively, suggesting that a muscarinic and an alpha-adrenergic receptor were involved. The ionophore A23187 reproduced these stimulations, and the stimulatory effects of carbamylcholine and epinephrine were inhibited in the absence of exogenous Ca++ and after EGTA depletion. Ca++ thus appears as a major regulator of PG production in the thyroid. TSH (0.06--10 MU/ml) and dibutyryl cAMP had no effect on the release of PGE2, PGF2 alpha, or TxB2 by dog thyroid in vitro.     

Effect of prostaglandins(PGs) on progesterone production by human cultured luteal cells and their ability of PGs production

The present study was designed to investigate whether or not prostaglandins(PGs) were produced by human luteal cells(HLC) and their effects on the luteal cells by monolayer culture. The following results were obtained. Cultured HLC secreted progesterone(P), prostaglandin F(PGF) and prostaglandin E(PGE) into a medium at concentrations of 276.6 +/- 38.6, 1.95 +/- 0.36, 2.44 +/- 0.45 ng/ml/1 X 10(5) cells/day (mean +/- SE), respectively. Cultured HLC was able to convert 14C-arachidonic acid to 14C-PGF2 alpha, 14C-PGE2. These two results indicated that HLC had the ability to produce PGF and PGE. Cultures were carried out in the presence of indomethacin (Ind), PGF2 alpha and PGE2 alone as well as in a combination. P production by HLC was reduced in the presence of Ind. P production in the presence of Ind+PGE2 was more than that in the presence of Ind alone. There was no significant difference in P production between the presence of Ind and Ind+PGF2 alpha. It was concluded that HLC had the ability to produce PGs and that PGE2 significantly stimulated P production in as low concentrations as HLC could produce physiologically while PGF2 alpha did not.     

Prostaglandin synthesis by isolated rat renal glomeruli.

The PGE2, PGF2 alpha and 6-keto-PGF1 alpha contents of the incubation medium of glomeruli isolated from rat kidney were measured at different times with or without addition of arachidonic acid. These prostaglandins accumulated progressively with time and reached equilibrium after 60--120 min incubation. Synthesis of the 3 prostaglandins was inhibited when indomethacin was added whereas it was markedly enhanced, mainly for PGE2, at increasing doses of arachidonic acid. Plateaus were reached above 5 micrograms/ml and concentrations corresponding to 50% of the maximum values were 2 micrograms/ml for PGE2 and PGF2 alpha, and 0.8 microgram/ml for 6-keto-PGF1 alpha. There were strictly linear relationships between PGE2 or PGF2 alpha productions and the concentration of glomerular protein. PGE2 and PGF2 alpha synthesis with or without arachidonic acid were maximum at 30--37 degrees C. PGE2 glomerular content was almost undetectable initially and increased with time. These data demonstrate that PGE2, PGF2 alpha and PGI2, in order of decreasing abundance, are synthesized by the glomerular cells and suggest that PGE2 and PGI2-sensitive glomerular adenylate cyclase activities and PGE2-sensitive renin synthesis may be stimulated by prostaglandins formed in the glomeruli themselves.     

Prostaglandin regulation of macrophage collagenase production.

The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibitions of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0 micrometer PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2- to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 micrometer. PGF2alpha had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase.     

Chronic regulation of ovarian oxytocin and progesterone release by prostaglandins: opposite effects in bovine granulosa and early luteal cells

Oxytocin is synthesized in the granulosa-derived large cells of the ruminant corpus luteum from a gene which is dramatically up-regulated in the first few days after ovulation. In this work, the regulation of granulosa and luteal cells by prostaglandins and insulin (or insulin-like growth factor-I; IGF-I) has been explored by comparing their effects on oxytocin and progesterone production in cell culture. In granulosa cells, chronic exposure to insulin (17 nmol/l) stimulated luteinization as indicated by increased release of oxytocin and progesterone. Prostaglandin F2 alpha (PGF2 alpha) alone had little effect, but synergized with insulin (or IGF-I) to increase the release of both these hormones. In direct contrast, insulin-stimulated oxytocin production by luteal cells was inhibited by PGF2 alpha. The half-maximal dose (EC50) for PGF2 alpha action in both cell preparations was similar (10-100 nmol/l). Dose-response studies revealed that PGF2 alpha increased the potency of insulin in granulosa cells (EC50 for insulin-stimulation of oxytocin release reduced from 141 to 13 nmol/l by 1 mumol PGF2 alpha/l), but not in luteal cells. Insulin-stimulated oxytocin release from granulosa cells was also synergistically increased by PGE1, PGE2 and forskolin, suggesting this effect to be mediated by adenylate cyclase-coupled PGE receptors. The results reveal that the effects of prostaglandins on oxytocin release are dependent on both the developmental stage of the target tissue and on the presence of other regulators of cellular differentiation. Moreover, they suggest that the increase in responsiveness to insulin and IGF-I, which appears to accompany luteinization in the cow, may be an effect of prostaglandins produced locally during the peri-ovulatory period.     

Effect of carprofen and indomethacin on gastric function and the content of prostaglandins E2 and F2 alpha in human gastric juice

The effect of indomethacin (2 X 50 mg daily) and carprofen (2 X 150 mg daily) on gastric secretion and the generation of prostaglandins PGE2 and PGF2 alpha in gastric juice, was investigated in a single blind cross-over study in eight healthy volunteers lasting one week. We observed no statistically significant change in basal and pentagastrin-stimulated gastric secretory parameters (outputs of gastric acid, N-acetyl-neuraminic acid and pepsin) before and after treatment with indomethacin and carprofen. However, an inhibitory effect was found on the output of PGE2 and PGF2 alpha after pentagastrin stimulation. While both drugs diminished the output of PGF2 alpha to a similar extent, carprofen exerted a markedly weaker inhibitory effect on the output of PGE2 than did indomethacin. It is suggested that the gastric tolerability of non-steroidal anti-inflammatory drugs (NSAIDs) is related to their inhibitory potency on PGE2 formation, in the sense that weak inhibitors of PGE2 cause less damage to the gastric mucosa than do strong inhibitors.     

The effects of angiotensin II and indomethacin on the pulmonary arterial prostaglandin E levels and pulmonary circulation in dogs.

We studied whether pulmonary arterial levels of plasma prostaglandin E rose following pressor effects of angiotensin II in the intact dogs. Furthermore, the modulation by indomethacin of the effect of angiotensin II, PGF2 alpha, and PGE1 on pulmonary circulation was evaluated. Pulmonary arterial plasma PGE levels rose significantly from 0.52 +/- 0.10 (SE) ng/ml to 0.85 +/- 0.07 by the infusion of angiotensin II. This increase was not observed when indomethacin was given. The rise in pulmonary arterial pressure and total pulmonary resistance by angiotensin II was augmented significantly with pretreatment of indomethacin. These results showed that there was an augmentation of the pulmonary vasoconstrictor action of angiotensin II as indomethacin blocked an increase of pulmonary arterial PGE level. Thus, it was suggested that prostaglandins (especially PGE) modulated the pulmonary vasoconstrictor effects of angiotensin II.     

Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides.

The mechanism by which renal prostaglandins stimulate renin secretion in vivo is unknown. In this in vitro study we measured the effects of activation of the prostaglandin (PG) system on renin release from slices of rabbit renal cortex. The PG precursor arachidonic acid (C20:4), a natural PG endoperoxide (PGG2), two stable synthetic PG endoperoxide analogues (EPA I and II), PGE2, PGF2alpha, and two different PG synthesis inhibitors [indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA)] were used to evaluate the possibility of a direct action of the cortical PG system on renin secretion. Renin release increased significantly with time after addition of C20:4, PGG2, EPA I, and EPA II to the incubation medium. Stimulation of renin release was se-related for C20:4 in concentrations of 0.6 to 4.5 X 10(-6) M, for EPA I in concentrations of 0.7 to 2.8 X 10(-6) M, and for EPA II in concentrations of 1.4 to 14.0 X 10(-6) M. Indomethacin (10(-4) M) and ETA (10(-4) M) significantly decreased basal renin release as well as the renin release stimulated by C20:4 and EPA I. PGE2(10(-12) to 10(-6) M) had no effect on renin release, whereas PGF2alpha (10(-12) to 10(-6) M) decreased renin release in a dose-dependent manner. These data raise the possibility of a direct action of the renal cortical PG system on renin secretion. The results further indicate that stimulation of renin release by C20:4 may depend more specifically on the action of PG endoperoxides than on the primary prostaglandins.     

Effects of oxygen, calcium ionophore, and arachidonic acid on prostaglandin production by monolayer cultures of mixed cells and endothelial cells from rat fetal lungs

Prostaglandins (PGs) synthesized by fetal and neonatal lungs play pivotal roles in pulmonary physiology, especially during the transition from uterine to independent life. One regulator of prostaglandin synthesis at this time may be oxygen. We examined the effects of 1% O2, 21% O2 and 50% O2 in 5% CO2, balance N2 (PO2 values in medium = 30 +/- 4, 142 +/- 4, and 260 +/- 3 mm Hg, respectively), on prostaglandin production from monolayer cultures of mixed or endothelial cells prepared from day 20 gestation rat fetal lungs. Cells were untreated or stimulated to produce prostaglandins by the addition of the calcium ionophore, A23187 (10(-5) M), or the prostaglandin precursor, arachidonic acid (AA, 1 microgram/ml). Prostaglandins 6-keto F1 alpha (6KF, the hydrolysis metabolite of prostacyclin, PGI2), E2, F2 alpha and 13,14-dihydro-15-keto PGF2 alpha (FM, the enzymatic metabolite of PGF2 alpha) were measured by radioimmunoassay. The basal release of 6KF from mixed cells into serum-free medium was approximately 2 ng/10(6) cells/3 days. The levels of 6KF were 10-fold greater than those of the other prostaglandins. Basal endothelial cell release of 6 KF was 30 ng/10(6) cells/3 days, and this was 15- to 100-fold greater than that of the other prostaglandins measured. In mixed cells, oxygen treatment for 3 days had no effect upon the basal release of any prostaglandin, nor was there any effect of oxygen upon the basal 6KF or PGE2 production in endothelial cells. However, both PGF2 alpha and PGFM production by endothelial cells was decreased (p less than 0.05) in 50% O2 compared to 1% O2. Both A23187 and AA enhanced prostaglandin release from mixed and endothelial cells. Ionophore-stimulated 6KF net production in mixed cells was greater in 21% O2 than in 1% O2 (p less than 0.05). Calcium ionophore stimulated the net production of 6KF and PGE2 in endothelial cells in 21% O2 versus 1% O2 (p less than 0.05), and AA enhanced the net production of 6KF, PGE2 and PGF2 alpha in endothelial cells in 21% O2 versus 1% O2. We conclude that rat fetal pulmonary cells produce prostaglandins from endogenous and exogenous substrates, that prostaglandin production is sensitive to Ca2+-mobilizing agents, and that the production of the vasodilators PGI2 and PGE2 increases in the presence of 21% O2 and a stimulating factor.     

Prostaglandins and steroidogenesis in isolated bovine adrenal cells. Effects of ACTH, prostaglandin-synthesis inhibitors, prostaglandins and prostaglandin analogs

In bovine adrenal cortex cells, dispersed without preferential loss of cells, we investigated (1) whether endogenous prostaglandins (PGs) are involved in ACTH-induced adrenal steroidogenesis, and (2) the steroidogenic effects of PGs and PG analogs. Free cells produced considerable amounts of PGE2, whereas only minute quantities of PGF2 alpha and PGA1 were synthesized. PGE2 synthesis, however, was not significantly increased when ACTH elicited a steroidogenic response in free cells. High concentrations of PG-synthesis inhibitors such as indomethacin affected both PG synthesis and steroidogenesis, whereas intermediate concentrations (10(-6) M) inhibited production of both PGE2 and aldosterone even after cAMP and cortisol response to ACTH had returned to normal values. It is concluded that endogenous PGE2 is not a link in the acute mechanism of action of trophic hormones in which cAMP is involved. Of the prostanoid structures, PGs of the E series were the most potent stimulating agents of cortisol production, although less active than ACTH. On the other hand, PGA1 induced an ACTH-like aldosterone synthesis. PGE2 was less active, and other prostanoid structures were without effect on aldosterone production. It is suggested that in pathological circumstances, PGA1 regulates aldosterone production and PGE2 increases both aldosterone and cortisol production.     

Effect of prostaglandins E2 and F2 alpha on membrane calcium binding, Ca2+/Mg2+-ATPase activity and membrane fluidity in rat myometrial plasma membranes

Myometrial plasma membrane (MPM) preparations from rats treated with oestradiol were obtained by discontinuous sucrose-gradient centrifugation. The preparations contained calcium-stimulated and magnesium-dependent ATPase (Ca2+/Mg2+-ATPase). A dramatic decrease in the activity of Ca2+/Mg2+-ATPase was observed when preparations were treated with 0.025-10 mumol prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha)/l. In contrast, there was a marked increase in MPM-bound 5'-nucleotidase activity at low concentrations (up to 2 mumol/l) of PGE2 and PGF2 alpha; higher concentrations (up to 10 mumol/l), however, led to a progressive inhibition of enzyme activity. Association (specific and non-specific binding) of PGE2 and PGF2 alpha with MPM at pH 7 was found to require Ca2+ (half-maximal concentration approximately 0.7 mmol/l). Changes in the allosteric properties of MPM-bound 5'-nucleotidase by concanavalin A (as reflected by changes in the Hill coefficient) indicated a fluidization of the membrane induced by PGE2 and PGF2 alpha. The steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene-labelled MPM decreased in PGE2- and PGF2 alpha-treated MPM from 1.24 +/- 0.04 (S.D.) to 0.66 +/- 0.01 and 0.74 +/- 0.01 respectively, which is consistent with a general increase in membrane fluidity. It is suggested that PGE2 and PGF2 alpha promote changes in the physical properties of MPM which may be relevant to the induction of uterine contractions by enzymatic regulation of intracellular calcium concentrations.     

Release of prostaglandins during reversal of one-kidney, but not two-kidney, one clip hypertension in the rat

Changes in systolic blood pressure and urinary excretion of PGE2 and 6-keto PGF1 alpha 24 h after removing the renal artery clip were compared in one-kidney and two-kidney, one clip Goldblatt hypertension in the rat. Unclipping the one-kidney rat returned blood pressure to normotensive levels within 24 h and was associated with a substantial increase in urinary PGE2 and 6-keto PGF1 alpha. Although hypertension was also completely reversed in the two-kidney model there was no significant change in urinary prostaglandin excretion. Prior treatment with indomethacin (6.0 mg/kg) markedly reduced urinary prostaglandins after clip removal in both forms of hypertension but attenuated the fall in blood pressure in the one-kidney model only. There were no significant changes in urinary kallikrein activity following unclipping. It is suggested that in the one-kidney, one clip rat prostaglandins are released as the result of exposing the unclipped kidney to elevated arterial pressure and that these contribute to the subsequent fall in blood pressure.     

Prostaglandin synthesis, metabolism, and signaling potential in the rhesus macaque corpus luteum throughout the luteal phase of the menstrual cycle

Prostaglandins in the corpus luteum (CL) reportedly serve as luteotropic and luteolytic agents. Based mainly on studies conducted in domesticated animals and rodents, prostaglandin E2 (PGE2) is generally considered a luteotropic factor, whereas uterine-derived prostaglandin F2alpha (PGF2alpha) initiates luteolysis. However, the role of prostaglandins in regulating primate luteal structure-function is poorly understood. Therefore, a comprehensive analysis of individual mRNA or proteins that are involved in PGE2 and PGF2alpha biosynthesis, metabolism, and signaling was performed using CL obtained at distinct stages of the luteal life span during the menstrual cycle in rhesus monkeys. Peak levels of proteins involved in PGE2 synthesis (prostaglandin-endoperoxide synthase 2, microsomal PGE2 synthase-1) and signaling (PGE2 receptor 3) occurred during periods corresponding to development and maintenance of the primate CL. Immunohistochemistry studies indicated that large luteal cells express PGE2 synthesizing and signaling proteins. Expression of PGE2 synthesizing and signaling proteins significantly decreased preceding the period of functional regression of the CL, which also coincided with increasing levels of PGF2alpha receptor protein expression within the large luteal cells. Moreover, significant levels of mRNA expression for several aldoketo reductase family members that synthesize PGF2alpha from other prostaglandins were observed throughout the rhesus macaque luteal phase, thus supporting the possibility of intraluteal PGF2alpha production. Collectively, our results indicate that there may be intraluteal synthesis and signaling of PGE2 during development and maintenance of the primate CL, followed by a shift to intraluteal PGF2alpha synthesis and signaling as the CL nears the time of luteolysis.     

Prostaglandin E1 inhibits DNA synthesis in arterial smooth muscle cells stimulated with platelet-derived growth factor

The effect of prostaglandins (PG) on initiation of DNA synthesis in arterial smooth muscle cells (SMC) stimulated with platelet-derived growth factor (PDGF) was examined. A concentration of 10 ng/ml PGE1 inhibited DNA synthesis, measured as autoradiographically labeled nuclei, by about 70%. Similar results were obtained with PGE2 and PGD2 but at concentrations 10-20 times higher, whereas PGF2 alpha lacked effect. The inhibitory action of the prostaglandins was restricted to the first 6 h of the lag phase. Treatment with PGE1 also raised the intracellular concentration of cyclic AMP, indicating that the inhibition may be mediated via changes in the levels of cyclic nucleotides.     

Effects of parathyroid hormone and cortisol on prostaglandin production by neonatal rat calvaria in vitro

We have examined the effects of parathyroid hormone (PTH) and cortisol on the production of prostaglandins, particularly PGE2, by neonatal rat calvaria cultured in a chemically-defined medium. Although there was considerable variability, calvaria produced large amounts of PGE2 in control cultures, reaching medium concentrations of 40 to 200 nM. PGE2 release was partially inhibited by cortisol at 10 nM and markedly inhibited at 100 nM. Bovine 1-34 synthetic PTH produced an increase in PGE2 concentration which was most striking in the presence of a low concentration of cortisol (10 nM). The medium also contained large amounts of 6-keto PGF1 alpha, the metabolite of prostacyclin, which showed similar changes in response to PTH and cortisol. Thromboxane B2 concentrations were low and unaffected by these hormones. 1,25-dihydroxyvitamin D did not increase medium PGE2 concentration. Since PGE2 is a potent stimulator of bone resorption and formation, some of the effects of PTH as well as cortisol may be mediated by their ability to alter PGE2 production in skeletal tissue.