Inhibitory Effect Of Prostaglandins Research Articles

P41 Hydrogen sulfide: Endogenous production and regulatory role in ocular tissues

Hydrogen sulfide (H 2 S), a colorless gas characterized by its pungent odor, has been portrayed for decades as a toxic pollutant. Evidence of endogenous production of H 2 S in mammalian tissues, and its potential biological role stimulated our interest in the pharmacological significance of this gaseous molecule in ocular tissues. In the present study, we tested the hypothesis that H 2 S is endogenously produced in mammalian ocular tissues, and may produce pharmacological effects in retinal pigment epithelial cells. Methods Endogenous levels of H 2 S were measured in bovine ocular tissues, using a well established colorimetric assay. In addition, basal level of H 2 S in bovine retina was examined in response to the H 2 S substrate, l -cysteine as well as the H 2 S biosynthetic enzymes inhibitors, propargylglycine (PAG) and aminooxyacetic acid (AOA); or activator, S-adenosyl- l -methionine (SAM). Using a H 2 S-releasing compound, sodium hydrosulfide (NaHS), we also determined the effects of H 2 S on cyclic AMP (cAMP) production in rat retinal pigment epithelial cells (RPE-J) by Enzyme Immuno Assay. The observed effect of H 2 S on cAMP was studied in the presence or absence of forskolin, an adenylate cyclase activator; glibenclamide, an ATP-sensitive potassium channel (K ATP ) antagonist; or flubiprofen and indomethacin, which are cyclooxygenase (COX) inhibitors. Results H 2 S is endogenously produced in ocular tissues with highest level detected in cornea (19 ± 2.85 nmoles/mg protein) and retina (17 ± 2.1 nmoles/mg protein). Interestingly, the inhibitors of cystathionine γ -lyase (CSE) and cystathionine β -synthase (CBS) (1 mM PAG and 1 mM AOA, respectively) significantly decreased H 2 S production in the bovine retina by 56.8 and 42%. On the other hand, activator of CBS (SAM, 100 μ M), and H 2 S substrate ( l -cysteine, 10–300 μM) increased ( p 2 S in bovine retina. In RPE-J cells, NaHS (1 nM–100 μM) produced a concentration-dependent increase ( p p ATP channel antagonist, glibenclamide (100 μM) inhibited the NaHS-induced increase of cAMP production in RPE-J cells. Conclusions Our results indicate that H 2 S is endogenously produced in various tissues in the bovine eye. Endogenous level of H 2 S is increased in the presence of l -cysteine or SAM, and decreased by PAG or AOA, inhibitors of enzymes that synthesize H 2 S in neural retina. Moreover, H 2 S can increase cAMP production in RPE-J cells, and removal of the apparent inhibitory effect of prostaglandins unmasks an excitatory effect of H 2 S on cAMP production. In addition to the adenylyl cylcase pathway, K ATP channels are involved in mediating the observed effects of H 2 S on cAMP production. The fact that H 2 S is endogenously produced in ocular tissues and exhibits a regulatory role in cyclic nucleotide production in retina, supports a physiological and/or pharmacological role for this gaseous molecule in the eye.

Nonsteroidal Anti-Inflammatory Drug-Induced Severe Hyponatremia

Hyponatremia (serum sodium level, <135 mmol/L) occasionally may develop in the course of treatment with nonsteroidal anti-inflammatory drugs, which are usually used in daily clinical practice. Nonsteroidal anti-inflammatory drugs diminish the normal inhibitory effect of prostaglandins on the activity of antidiuretic hormone and can therefore reduce free water excretion, leading to water retention and induction or exacerbation of hyponatremia. In this report, we present a case of hyponatremia in a 78-year-old man who had received meloxicam, a nonsteroidal anti-inflammatory drug.

Arsenic content in Portland cement: A literature review

Portland cement (PC) is a hydraulic binding material widely used in the building industry. The main interest in its use in dentistry is focused on a possible alternative to mineral trioxide aggregate (MTA) because PC is less expensive and is widely available. In dentistry, PC has been used in dental procedures such as pulpotomy, pulp capping, repair of root perforation and root-end filling. The purpose of this article is review the dental literature about the PC, its composition with special attention to arsenic content, properties, and application in dentistry. A bibliographic research was performed in Bireme, PubMed, LILACS and Scopus data bases looking for national and international studies about the PC composition, properties and clinical use. It was observed that PC has favorable biological properties very similar to those of MTA. The PC has shown good cell proliferation induction with formation of a monolayer cell, satisfactory inflammatory response, inhibitory effect of prostaglandin and antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the apposition of reparative dentin and permits cellular attachment and growth. Regarding arsenic presence, its levels and release are low. PC has physical, chemical and biological properties similar to MTA. Arsenic levels and release are low, therefore, unable to cause toxic effects.

Prostaglandin analogue misoprostol attenuates neurotoxin 1-methyl-4-phenylpyridinium-induced mitochondrial damage and cell death in differentiated PC12 cells

Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The present study assessed the preventive effect of a prostaglandin E 1 analogue misoprostol against the toxicity of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP +) with respect to the mitochondria-mediated cell death process and oxidative stress. MPP + induced the nuclear damage, the changes in the mitochondrial membrane permeability, the formation of reactive oxygen species and the depletion of GSH, which leads to cell death in differentiated PC12 cells. Misoprostol prevented the toxic effect of MPP +. Treatment with misoprostol significantly attenuated the MPP +-induced mitochondrial membrane permeability change that leads to the increase in pro-apoptotic Bax and Cytochrome c levels, and subsequent caspase-3 activation. The protective effect of misoprostol may be supported by the inhibitory effect of prostaglandin E 1 on the MPP + toxicity. Misoprostol significantly attenuated another parkinsonian neurotoxin rotenone-induced cell death. The results show that misoprostol may prevent the MPP + toxicity by suppressing the mitochondrial membrane permeability change that leads to the Cytochrome c release and caspase-3 activation. The preventive effect seems to be ascribed to the inhibitory effect on the formation of reactive oxygen species and depletion of GSH.

Inhibitory effect of prostaglandin E 1 on intimal thickening caused by poor runoff conditions in the canine autologous vein grafts.

The efficacy of ONO-1608, a newly developed liposomal formulation of prostaglandin E 1 prodrug, was evaluated on intimal hyperplasia of experimental canine autologous vein grafts under distal poor runoff conditions. The femoral vein was implanted into the femoral artery, preparing a distal poor runoff canine model. After 4 weeks of preparing the poor runoff model, the femoral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 weeks, the grafts were harvested and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine incorporation 2 weeks after surgery. In addition, the effect of ONO-1608 on the proliferation of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was also investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control group. The bromodeoxyuridine labeling index 2 weeks after grafting was significantly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-stimulated HASMCs in culture. These results demonstrate the efficacy of ONO-1608 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of ONO-1608 may be beneficial in patients who have undergone gone arterial reconstruction.

Virulizin® - a review of its antineoplastic activity

Virulizin® (registered trademark of Lorus Therapeutics, Inc.) is a novel biological response modifier (BRM) that enhances cell-mediated immune response to tumour cells by direct macrophage activation. The agent, an aqueous solution containing a 5% (w/v) solid material mixture comprised of inorganic salts (95 - 99% of the dry weight) and organic compounds of molecular weight << 3000 Daltons (1 - 5% of the dry weight), is provided as a sterile, injectable formulation. Virtually all the organic compounds and ionic components in the mixture have been identified by chemical and spectroscopic methods. Virulizin® is obtained from bovine bile by a standardised process involving solvent extraction and heat hydrolysis. In vitro studies have shown that Virulizin® can stimulate blood monocytes, peritoneal macrophages and alveolar macrophages from patients with malignant and non-malignant diseases to mediate a level of tumour cell cytolysis that is equal to, or greater than, that elicited in the same cells by other, more conventional biological activators. Other studies have shown that the stimulation of cytotoxic function by Virulizin® is insensitive to the inhibitory effects of prostaglandins and, hence, is distinct from many other activators. Furthermore, the blood monocytes of patients currently receiving cytotoxic chemotherapy showed activation with Virulizin®. In preclinical studies, Virulizin® showed modest inhibition of tumour growth in a human pancreatic cancer xenograft model (T/C, 0.60; p = 0.012) and increased survival time by 8% (p = 0.046) in a murine melanoma model. Toxicity studies in rats indicated that Virulizin® injected intramuscularly was well-tolerated by the animals. Except for a lower rate of body weight gain in the high dose group, no toxicological effect related to treatment was observed in a chronic 13-week study (three weekly im. injections of up to 1.1 ml/kg). Mutagenicity studies with Virulizin® were negative. Many Phase I/II and Phase II clinical trials were carried out with Virulizin® to evaluate the safety and efficacy of the agent to treat cancer patients. Three of those studies involved the treatment of patients with pancreatic adenocarcinoma. The majority of patients participating in these studies were those who had failed conventional treatment including surgery or chemotherapy. Disease stabilisation was observed in patients treated with Virulizin®, and, based on a meta-analysis of the data from the three studies, the survival of the patients treated with Virulizin® was better than a similar patient population receiving standard chemotherapeutic agent for that disease indication. However, randomised studies may be required to confirm the effect of Virulizin® on disease stabilisation and survival. In the three studies on patients with malignant melanoma, at least 69% treated with Virulizin® showed no additional deterioration or had improved at four weeks with response being only slightly reduced after eight weeks. In the evaluation of safety, assessed overall from these clinical studies in 200 patients treated with Virulizin®, the number and severity of adverse events were small. In conclusion, Virulizin® is a novel, clinically non-toxic biological response modifier that appears to have a clinical effect on disease stabilisation and survival in patients with pancreatic cancer and malignant melanoma. However, additional randomised studies may be required to confirm those effects. Future studies on Virulizin® will focus on the characterisation of the active components in the agent and the development of a synthetic formulation. Subsequently, the preclinical and clinical pharmacokinetics of Virulizin® will be determined and studies to optimise the human dose of the agent will be carried out.

Inhibitory Effects of Prostaglandin D 2 Against the Proliferation of Human Colon Cancer Cell Lines and Hepatic Metastasis from Colorectal Cancer

Inhibitory Effects of Prostaglandin D 2 Against the Proliferation of Human Colon Cancer Cell Lines and Hepatic Metastasis from Colorectal Cancer

The Lack of Bimodality in the Effects of Endogenous and Exogenous Prostaglandins on Fat Cell Lipolysis in Rats

The aim of this study was to investigate and clarify the role of prostaglandins (PG) on fat cell lipolysis in female rats. Incubations with adenosine deaminase (ADA) were used for the deamination of endogenous adenosine and increased basal (155%) and isoproterenol (10 −9 M) (348%) stimulation of glycerol release from adipocytes. Indomethacin and aspirin increased the effects of ADA while indomethacin further increased isoproterenol (with ADA) stimulation of lipolysis ( p ≤ 0.05). Exogenous PGE 2 and PGI 2 inhibited the isoproterenol and ADA stimulation of fat cell lipolysis ( p ≤ 0.05). The expected stimulatory effect of high concentrations of PGE 2 and of low concentrations of PGI 2 was not observed in the presence of ADA. Dose-response curves revealed that the inhibitory effects of PGs were reached at lower concentrations for PGE 2 than for PGI 2 ( p ≤ 0.05). In conclusion, this study showed that endogenous and exogenous PGs of adipose tissue only express an antilipolytic action on fat cell lipolysis. This effect appears to be highly significant when the β-adrenergic pathway is stimulated. Our results also stress the need to control the antilipolytic effects of adenosine to study the regulation of fat cell lipolysis by PGs.

Inhibitory effect of prostaglandin (PG) D 2, PGJ 2 and Δ 12-PGJ 2 on proliferation of cells involved in host defense

Inhibitory effect of prostaglandin (PG) D 2, PGJ 2 and Δ 12-PGJ 2 on proliferation of cells involved in host defense

Inhibitory effect of prostaglandin E 1 on intimal thickening following photochemically induced endothelial injury in the rat femoral artery

The inhibitory effect of prostaglandin E 1, which has an anti-platelet action and a vasodilating action via intracellular cyclic AMP elevation, was studied on intimal thickening in the rat femoral artery. A segment of the femoral artery was occluded by a platelet and fibrin-rich thrombus due to photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after endothelial injury, intimal thickening occurred at the irradiated site. Prostaglandin E 1 (0.3 μg/kg per min), administered as a continuous infusion 10 min before photochemical reaction significantly ( P<0.05) prolonged the time to occlusion of the femoral artery. In a separate experiment, prostaglandin E 1 (0.3 μg/kg per min) administered as a continuous infusion for 7 days just after endothelial injury significantly ( P<0.05) inhibited intimal thickening compared with a control group. In cultured rat-derived vascular smooth muscle cells, prostaglandin E 1 produced concentration-dependent inhibition of migration and proliferation, stimulated by platelet-derived growth factor. These results suggest that prostaglandin E 1 may be effective in preventing vascular restenosis after vascular surgery and angioplasty.

In vitro studies on the regulation of rainbow trout ( Oncorhynchus mykiss) macrophage respiratory burst activity

Modulation of the respiratory burst activity of head kidney macrophages isolated from rainbow trout ( Oncorhynchus mykiss) was observed following treatment with several biologically active substances. Macrophage-activating factor (MAF) induced the highest increment in respiratory burst activity relative to treatment with lipopolysaccharide (LPS), tumor necrosis factor a (TNFα) or β-glucans from Saccharomyces cerevisiae. Increased responses were more evident when these molecules were combined in pairs. Negative regulation of respiratory burst activity was observed when diMePGE 2 was added to the macrophages, with maximal inhibition seen using a concentration of 2.6 μ M. Inhibition was also seen using stimulated macrophages, either by co-incubation of stimuli and diMePGE 2 or by adding diMePGE 2 to previously stimulated cells. The inhibitory effect on macrophages was detectable within 3 h of incubation with diMePGE 2 and by 24 h the level of the response was even lower than that from unstimulated (control) macrophages. Of significance was the finding that the inhibitory effect of prostaglandin on macrophage function could be overcome by co-incubation with stimulatory molecules or by pre-treatment with MAF and LPS or MAF and TNFα Thus, the regulation of macrophage activation in fish is likely to be as complex as in mammals.

Prostaglandin E 2, but not prostacyclin inhibits histamine-induced contraction of human bronchial smooth muscle

The effects of exogenous prostaglandin E 2 and prostacyclin on the function of epithelium-intact and epithelium-denuded human bronchial smooth muscle and the role of these mediators in the inhibition of histamine-induced contraction was examined using bronchi obtained from 22 patients undergoing thoracotomy. Under resting tension, a variable biphasic contraction-relaxation or monophasic relaxation was observed following the cumulative addition of exogenous prostaglandin E 2 or prostacyclin. Cumulative addition of these mediators to pre-contracted bronchi produced incomplete relaxation, irrespective of the presence of epithelium. Addition of prostaglandin E 2, at a concentration equating to that produced after histamine stimulation (1.2 × 10 −9 M), produced a reduction (24%) in the maximum contractile response ( E max) to a subsequent histamine challenge ( P < 0.03). However, a similar response was not observed after the addition of prostacyclin at a concentration similar to that produced endogenously (6.5 × 10 −10 M). The combined addition of both mediators resulted in a significant reduction (26%) in the E max to histamine ( P < 0.02) but this effect was not statistically different to that of prostaglandin E 2 alone. The addition of supramaximal concentrations (1 μM) of each prostanoid, either alone or in combination, did not inhibit responses to histamine. These data suggest that whilst prostaglandin E 2 does not act as a direct acting relaxant agonist, it may inhibit histamine-induced muscle contraction and thereby contribute to the observed tachyphylaxis to this mediator. In contrast, prostacyclin appears to be of little importance in modulating human bronchial smooth muscle responses to histamine either directly or by enhancing responses to prostaglandin E 2. The inhibitory effect of prostaglandin E 2 appears to be concentration-dependent and suggests a bimodal action of this mediator in human airways.

Inhibitory effect of prostaglandins on dopamine release from the retina

1. Prostaglandins have been shown to modulate transmitter release from both central and peripheral neuroeffector junctions. In the present study, we examined the effect of prostaglandins on [ 3H]-dopamine release from isolated, superfused rabbit retina. 2. Both naturally occurring and synthetic prostaglandins produced concentration-dependent reduction of electrically evoked [ 3H]-dopamine overflow without affecting basal tracer efflux. The rank order of potencies of the agonists was: sulprostone > 16, 16-dimethyl PGE 2>PGE 2> > 11-deoxy-PGE 1>PGF 2 α . 3. The PGE 2-mediated inhibition of field stimulated [ 3H]-dopamine release was not blocked by the selective EP 1-receptor antagonist, AH6809 (5–30 μM). 4. The cyclooxygenase inhibitor, flurbiprofen (3 μM) had no effect on basal or evoked [ 3H]-dopamine overflow nor did it affect the inhibition caused by PGE 2 suggesting that endogenous prostaglandins are not involved in the regulation of dopamine release in the retina. 5. The inhibition of [ 3H]-dopamine release produced by submaximal concentrations of PGE 2, apomorphine and melatonin were not additive indicating that presynaptic PGE 2, D 2- and melatonin receptors coexist at sites for neurotransmitter release and may share a common mechanism for regulation of dopamine release. 6. We conclude that prostaglandin-induced inhibition of electrically evoked [ 3H]-dopamine release from the rabbit retina may be mediated by specific prostaglandin receptors of the EP 3 subtype.

Influence of prostaglandins and a prostaglandin H synthase inhibitor on cervical secretion of the guinea-pig.

The modulatory effects of several prostaglandins and a prostaglandin H synthase inhibitor (indomethacin) on basal as well as nerve stimulation induced secretion from the cervical glands of the guinea-pig were studied. Hypogastric nerve stimulation resulted in a secretory response of +113%. Indomethacin dose dependently inhibited this secretory response. Prostaglandins E2, F2 alpha and I2 inhibited and 19-OH prostaglandin E1 reduced nerve stimulation induced secretion. Prostaglandin I2 and 19-OH PGE1 markedly enhanced basal secretion, while indomethacin as well as PGE2 and PGF2 alpha did not induce any secretion of cervical glands. However, PGF2 alpha in combination with the alpha-adrenergic blocker phentolamine resulted in an increase in secretion. The inhibitory effect of prostaglandins on cholinergic secretory innervation might be due to stimulation of adrenergic nerves exerting an inhibitory influence on cholinergic secretomotor innervation. It is suggested that PGI2 and 19-OH PGE1 exert postjunctional stimulatory effects on the secretory lining and that a lack of secretory effect of PGF2 alpha at least in part may be due to stimulatory effects on adrenergic neurons, inhibiting cholinergic secretomotor transmission. Thus, in this in vitro study it is shown that metabolites of the arachidonic acid cascade and a prostaglandin H synthase inhibitor can modulate cervical secretion and thus maybe influence fertilization.

Inhibitory effect of prostaglandin Δ 12-PGJ2 on cell proliferation and α-fetoprotein expression in HuH-7 human hepatoma cells

9-deoxy-Δ 9, Δ 12-13,14-dihydro-prostaglandin D2 (Δ 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of Δ 12-PGJ2 on the α-fetoprotein (AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. Δ 12-PGJ2 inhibited the cell growth and reduced the medium AFP concentrations dose-dependently. To determine whether this decline of AFP depends only on the relative decrease in cell numbers by Δ 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by Δ 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that Δ 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the β-actin mRNA was not changed by Δ 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, Δ 12-PGJ2 did not suppress the AFP enhancer activity, which possibly regulates both the AFP and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the selective repression of the AFP and the albumin promoter activity. These results suggest that Δ 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells.

Prostaglandin E 1 suppression of platelet aggregation response in schizophrenia

The inhibitory effects of prostaglandin E 1 (PGE 1) on the platelet aggregation response (PAR) to adenosine diphosphate (ADP) in 103 schizophrenics, 55 patients with other mental disorders, and 71 controls were examined. The three groups did not differ in PAR to ADP. However, schizophrenic patients, especially in the acute state, showed a significant reduction in the inhibitory effects of PGE 1 on PAR compared to the other two groups. These results suggest PGE 1 hyposensitivity exists in some schizophrenic patients, which may result from PGE 1 deficiency. As clinical characteristics of the subgroup showing platelet PGE 1 subsensitivity, relatively successful heterosexual relations, less anergia, and a more severe activation factor on BPRS were identified. Furthermore, the relationship between platelet sensitivity to PGE 1 and brain morphology, using magnetic resonance imaging on 39 male schizophrenics was examined. Of 11 parameters obtained from MRI measurements, only callosum: brain ratio showed a significant negative correlation with a platelet sensitivity to PGE 1. The current study suggested existence of a subgroup of schizophrenia having platelet hyposensitivity and a definite clinical feature as state markers and small corpus callosum as a trait marker.

P-443 - Inhibitory effects of prostaglandin (PG) D2, J2, and Δ12PGJ2 on cell growth of human astrocytoma cells

P-443 - Inhibitory effects of prostaglandin (PG) D2, J2, and Δ12PGJ2 on cell growth of human astrocytoma cells

Characterization of hormone-sensitive adenylate cyclase in rabbit gallbladder mucosa

1. 1. We have developed a plasma membrane preparation from the mucosal epithelium of rabbit gallbladder and have characterized the hormonal sensitivity of adenylate cyclase in this preparation. 2. 2. Basal activity is low and is stimulated by GTP and GppNHp. Hormonal stimulation is largely dependent on exogenous guanine nucleotide. 3. 3. Several prostaglandins (E 1 ∼ E 2 > A 1 > B 1), vasoactive intestinal peptide and the β-adrenergic agonist, isoproterenol, stimulate mucosal adenylate cyclase activity; a variety of peptides and neurotransmitters (secretin, cholecystokinin, arg-vasopressin, oxytocin, histamine, dopamine and serotonin) are without effect. 4. 4. The data support the hypothesis that the inhibitory effect of prostaglandins, vasoactive intestinal peptide, and isoproterenol on gallbladder fluid absorption in certain species may be mediated by cyclic AMP. 5. 5. The membrane preparation should be useful in further characterizing hormone receptor-transducer interactions of the gallbladder mucosal epithelium.

Potential role for interleukin-1 in fibrosis associated with chronic ambulatory peritoneal dialysis.

Cytokines released by inflammatory cells can modify migration, proliferation and matrix protein synthesis by mesenchymal cells. Interleukin-1 (IL-1) produced by monocytes is one cytokine which could play a role in inducing peritoneal fibrosis in patients undergoing chronic peritoneal dialysis. IL-1 increases collagen synthesis associated with increased levels of procollagen mRNAs in fibroblasts. In some fibroblasts, this increase may be masked by the inhibitory effects of prostaglandins and revealed in the presence of cyclooxygenase inhibitors. Other known cytokines act similarly to IL-1 and may be synergistic with IL-1. The lymphokine interferon-gamma inhibits collagen synthesis. These mediators function in a complex network of feedback and amplification loops to regulate collagen deposition in inflammatory conditions.

On the specificity of prostaglandin and steroid induced inhibition of 3H-proline incorporation in the human follicular wall.

Experiments were carried out to elucidate whether the previously reported inhibitory effect of prostaglandin (PG) E2 on 3H-proline incorporation into total protein of specimens from the isolated preovulatory human follicular wall could be exerted also by other prostanoids. Moreover, investigations were designed to explore if the previously documented inhibitory effect of steroids on 3H-proline incorporation could be mediated by endogenously formed PGs. Tissue specimens from the apical wall of follicles were incubated in the presence of PGF2 alpha, 6-keto-PGF1 alpha, progesterone (P) or 17 beta-estradiol (E2). The steroids were added alone or in combination with the PG synthetase blockers, indomethacin or 5, 8, 11, 14-eicosatetraynoic acid. Following incubation with 3H-proline for 2-4 h, the incorporated radioactivity was determined. PGF2 alpha and 6-keto-PGF1 alpha had no effect on 3H-proline incorporation. Both P and E2 induced a significant decrease of 3H-proline incorporation in preovulatory follicles, whereas similar effects in unripe follicles were statistically significant only for P. The steroid effects were not influenced when blockers of PG synthesis were added concomitantly. It is concluded that among the "classical" PGs PGE2 has a unique effect on collagen metabolism in the human follicular wall. E2 and especially P have a similar inhibitory effect on collagen formation as reflected by measurements of 3H-proline incorporation, an effect which does not appear to be primarily mediated by endogenous PGs.