Biomedical subjects

F Saji

Publications and source records attributed to F Saji.

At least 91 records · Page 5Linked to original sources

PubMed1993

Inhibitory effects of estrogen, progesterone, androgen and glucocorticoid on death of neonatal mouse uterine epithelial cells induced to proliferate by estrogen.

Female newborn mice were given daily injections of estradiol-17 beta (E2; 25 micrograms/mouse/day) for 4 days from the day of birth, and uterine cell death after this E2 priming was investigated by examining the apoptotic index (percentage of apoptotic cells), and the retention of 3H-radioactivity incorporated into epithelial or stromal DNAs after injection of [3H]thymidine into the mice on the day after birth. With injections of vehicle only after E2 priming, the apoptotic index of the uterine epithelium increased markedly, being maximal on day 4 of injections, and the 3H-radioactivity retained in the epithelium decreased rapidly. Agarose gel electrophoresis of uterine epithelial DNAs on day 4 of injections showed a ladder pattern, characteristic of apoptotic cell death. However, daily injections of E2 (7.2 micrograms/g body wt) completely inhibited the increase in the apoptotic index and the loss of 3H-radioactivity in the epithelium. Daily injections of progesterone (80 micrograms/g body wt), 5 alpha-dihydrotestosterone (DHT; 8 micrograms/g body wt), and dexamethasone (2 micrograms/g body wt) also inhibited both parameters, although not completely. The inhibitory effects of DHT and progesterone were abolished by the antiandrogen, flutamide and antiprogesterone, RU 486, respectively. In contrast, no apoptotic cells and no loss of 3H-radioactivity were found in the stroma for any treatment after E2 priming. The present results suggest that discontinuation of estrogen stimulation results in apoptotic cell death in the uterine epithelium of neonatal mice, but not in the stroma, and that estrogen, progesterone, DHT and dexamethasone inhibit cell death of uterine epithelium.

Animals↗

PubMed1993

Placental interleukin-6 production is enhanced in intrauterine infection but not in labor.

OBJECTIVE: Because interleukin-6 is an important mediator in the host defense mechanism against infection and tissue damage, we studied the capacity of placentas with or without either labor or chorioamnionitis in the third trimester to produce interleukin-6. STUDY DESIGN: The placental blocks were cultured, and their interleukin-6 titers were measured by a bioassay. RESULTS: Placentas with labor produced a similar amount of interleukin-6 to placentas without labor. In contrast, placentas with chorioamnionitis produced much more interleukin-6 than the placentas with or without labor (p < 0.0001). CONCLUSION: Placental interleukin-6 is thus surmised to participate in potentiation of the placental and fetomaternal defense mechanisms together with placental interleukin-1 during chorioamnionitis.

Chorioamnionitis↗

PubMed1993

Membrane-spanning Fc gamma receptor III isoform expressed on human placental trophoblasts.

PROBLEM: Fc receptor for immunoglobulin (Fc gamma R) is an important mediator of immunological functions in the feto-maternal relationship. We have demonstrated by immunohistochemical means that three distinct classes of Fc gamma Rs are expressed in the different cell components of the human placenta. METHOD: In this study, Fc gamma RIII isoform expressed on placental trophoblasts (PTs) was investigated by indirect immunofluorescence and cDNA cloning. PTs, isolated from human term placenta by digestion with proteolytic enzyme, were reacted with monoclonal antibodies (MAb) against the Fc gamma Rs and other surface markers of leukocytes and subjected to flow cytometric analysis. RESULTS: PTs were positively stained with 3G8 and Leu1 1b against Fc gamma RIII, partially stained with MAb against MHC class I, but not with 32.2 (Fc gamma RI), IV3 (Fc gamma RII), or MAbs against CD4, CD19, or CD56, indicating that only low affinity receptor, Fc gamma RIII, is expressed on PTs. The DNA sequence of cloned Fc gamma RIII CDNA from PTs by PCR was identical to that of natural killer (NK) cell isoform, including the position of the stop codon that differs from the granulocyte isoform by several nucleotide substitutions. We further analyzed the susceptibility of PTs against phosphatidylinositol specific phospholipase C (PI-PLC) to determine the structural topology of PT isoform. While the reactivity with 3G8 on PTs was not influenced by treatment with PI-PLC, that on granulocytes was significantly diminished with PI-PLC. CONCLUSIONS: This result confirmed that Fc gamma RIII on PTs is a membrane-spanning molecule, and that it is distinctive from PI anchoring Fc gamma RIII on granulocytes.

Antibodies, Monoclonal↗

PubMed1993

Expression and localization of oxytocin receptor gene in human uterine endometrium in relation to the menstrual cycle.

The expression of oxytocin receptor mRNA in the human uterus was investigated by polymerase chain reaction after mRNA reverse transcription; in addition, the mRNA was localized by means of in situ hybridization histochemistry. Strong positive signals were observed in myometrial cells at parturition. In nonpregnant human uterine endometrium, oxytocin receptor mRNA was expressed in glandular epithelial cells, but was not observed in stromal cells. The signal in the epithelial cells was stronger at the time of ovulation than during any other phase. The sequential changes in oxytocin receptor mRNA expression in nonpregnant endometrium suggest some alternative biological function of oxytocin in endometrium during the menstrual cycle.

Base Sequence↗

PubMed1993

The interleukin-6 (IL-6)/IL-6-receptor system induces human chorionic gonadotropin production by activating tyrosine kinase-dependent signal transduction pathway different from pathways triggered by protein kinase activators including gonadotropin releasing hormone.

Interleukin-6 (IL-6) may play an important role in human CG (hCG) production by activating the IL-6-receptor (-R) system on human trophoblasts. Trophoblasts produced hCG in response to rIL-6 as well as to 8-bromo cAMP (8-Br-cAMP), 12-O-tetradecanoyl phorbol-13-acetate (TPA), and calcium ionophore A23187. To determine whether the signal transduction pathway activated by the IL-6-R system depends on protein kinases such as protein kinase A, protein kinase C, and Ca2+/calmodulin-dependent kinase, trophoblasts were stimulated with recombinant (r-) IL-6 in the presence or absence of protein kinase inhibitors such as N(2-methyl-aminoethyl)-5-isoquinoline sulfonamide dihydrochloride (H8), and 1-(5-isoquinolinesulfomyl)-2-methylpiperazine (H7) and a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1- napthalenesulfonamide (W7), H8, H7, and W7 failed to suppress rIL-6-induced hCG production but completely inhibited hCG production induced by 8-Br-cAMP, TPA, and the GnRH agonist (GnRHa), respectively. In contrast, genistein, a tyrosine kinase inhibitor, completely suppressed rIL-6-induced hCG production but failed to inhibit hCG production induced by 8-Br-cAMP, TPA, and A23187. Genistein also did not suppress GnRH-induced hCG production. The addition of genistein to rIL-1- and rTNF-alpha-stimulated trophoblasts inhibited rIL-1-induced and rTNF-alpha induced hCG production but maintained rIL-1- and rTNF-alpha-induced IL-6 production. These results show that the IL-6/IL-6-R system-induced signal transduction pathway in the placenta probably stimulates hCG production by activating a tyrosine kinase pathway. The experiment with genistein shows that the GnRH/GnRH-R system activates a signal transduction pathway distinct from that activated by the IL-6/IL-6-R system.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

[Application of DNA fingerprinting to obstetrics and gynecology].

Restriction fragment length polymorphisms (RFLP) are variations in the size of restriction fragments of genomic DNA that hybridize to specific probes. They are the consequence of changes in primary DNA sequences, most of which result from small-scale changes in DNA. Recently minisatellite DNA probes that detect many regions of great variability within the human genome have been described. Minisatellite probes consist of multiple repeated copies of a common 10-15 base pair core sequence. On hybridization to restriction enzyme digests of human DNA, they simultaneously detect many highly polymorphic minisatellites at different loci in the genome, and produce band patterns that are individual specific. The band patterns are called "DNA fingerprints" or "DNA barcode" which can be used for individual identification on forensic and legal medicine. In addition to forensic and legal medicine, DNA fingerprinting can be used in both basic research and clinical examination of obstetrics and gynecology. The RFLP bands in DNA fingerprinting are inherited as single Mendelian co-dominants and we can use such minisatellite DNA probe for the determination of zygosity in multiple pregnancy. This probe can be used for the determination of androgenesis as a cause of complete hydatidiform mole. Each polymorphic band in molar tissues could be identified as being of paternal but not maternal origin. Some polymorphic bands of paternal origin were not observed in molar tissues, indicating that endoreduplication of a normal haploid sperm or fertilization by dispermy to an anuclear oocyte with no effective genome could be the cause of complete hydatidiform mole (androgenesis).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Detection of interleukin-8 (IL-8) in seminal plasma and elevated IL-8 in seminal plasma of infertile patients with leukospermia.

OBJECTIVE: To determine if interleukin-8 (IL-8) is a normal constituent of seminal plasma and if leukospermia is a factor determining its elevation. DESIGN: Seminal plasma from 58 men obtained by masturbation was examined for the presence of IL-8 using an IL-8 specific sandwich ELISA. Semen samples were obtained from 34 infertile men without leukospermia, 10 infertile men with leukospermia, and 14 proven fertile men. The correlation of amount of IL-8 in seminal plasma with some spermiogram parameters and the amount of polymorphonuclear (PMN) elastase was statistically evaluated. RESULTS: Immunoreactive IL-8 was observed in the seminal plasma of all 58 subjects. The IL-8 titer in seminal plasma of patients with leukospermia (6.16 +/- 0.82 micrograms/L) was significantly higher than that in seminal plasma of patients without leukospermia (2.35 +/- 0.34 micrograms/L) and fertile men (1.64 +/- 0.29 micrograms/L). There was a high degree of correlation between PMN elastase and IL-8 levels in seminal plasma. CONCLUSIONS: These findings demonstrate IL-8 to be in seminal plasma and elevated IL-8 levels in infertile patients with leukospermia.

Humans↗

PubMed1992

Histogenetic analysis of ovarian germ cell tumors by DNA fingerprinting.

The histogenesis of ovarian germ cell tumors (11 mature teratomas, three malignant transformations of mature teratomas, two immature teratomas, and four dysgerminomas) was investigated genetically using minisatellite DNA probes 33.15 and 33.6 for person-specific restriction fragment length polymorphism (DNA fingerprint) analysis. The DNA fingerprints of six ovarian teratomas were identical with those of mononuclear cells from each host, while some polymorphic bands observed in the host mononuclear cells were lost in the DNA fingerprints of the other five cases. The cases of malignant transformation of mature teratoma and immature teratoma showed that some polymorphic bands of DNA fingerprints from the host mononuclear cells were absent in the tumor tissues. In four cases with dysgerminomas, the DNA fingerprints of tumors were completely identical with those of the respective host mononuclear cells. The present results suggest that mature cystic teratomas of the ovary arise from germ cells arrested at various stages of meiosis, while immature teratomas are derived from postmeiotic germ cells. Malignant transformation may occur exclusively in the mature teratomas arising from postmeiotic germ cells. Dysgerminomas develop from premeiotic oogonia (primordial germ cells). Thus, DNA fingerprints are a useful and sensitive tool for identifying the pathogenesis of germ cell tumours.

Adolescent↗

PubMed1992

Malignant cell-specific gelatinase activity in human endometrial carcinoma.

BACKGROUND: The protease activity leading to degradation of the extracellular matrix was compared between human endometrial cancer and normal uterine endometrium. METHODS: Conditioned medium from tumor cells and normal endometrial cells was subjected to electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gel containing gelatin as a substrate. After electrophoresis, the gel was stained with Coomassie blue, and then the enzyme activity, expressed as the zone of dye clearing, was analyzed by densitometry. RESULTS: Densitometric analysis showed that all the endometrial cancers expressed a very high molecular weight enzyme activity (Mr 220,000), which was not detected in medium from normal endometrial cells. The analysis also showed that in endometrial cancer the activity of a Mr 92,000 enzyme was always superior to that of a Mr 64,000 enzyme, which was in contrast to the situation for normal endometrium. CONCLUSIONS: These results indicate that the expression of Mr 220,000 enzyme activity and the higher activity of the Mr 92,000 enzyme than the Mr 64,000 enzyme are involved in the malignant phenotype of native endometrial cancer.

Adenocarcinoma↗

PubMed1992

Triplet pregnancy involving complete hydatidiform mole and two fetuses: genetic analysis by deoxyribonucleic acid fingerprint.

A case of a triplet pregnancy involving a dizygous twin pregnancy and a complete hydatidiform mole after therapy with human menopausal gonadotropin and human chorionic gonadotropin is reported. Two female fetuses, two placentas in one mass with two amnions and two chorions, and a tumor mass with a grapelike appearance were spontaneously delivered at 19 weeks of gestation. The deoxyribonucleic acid fingerprints of the two placentas and tumor tissue were compared with those of the parents. The fingerprints of the placentas showed patterns different from each other; however, all their polymorphic fragments could be traced back to either the father or mother. All polymorphic fragments of the tumor tissue were inherited only from the father (androgenesis). These results indicated that this triplet pregnancy involved a dizygous twin pregnancy and a complete hydatidiform mole.

Adult↗

PubMed1992

Estimation by an electrophysiological method of the expression of oxytocin receptor mRNA in human myometrium during pregnancy.

In order to evaluate the changes in uterine oxytocin receptor-specific mRNA during pregnancy, receptor expression in Xenopus oocytes are examined electrophysiologically following microinjection of mRNA from human uterus. In voltage-clamped oocytes injected with term myometrial mRNA, oxytocin elicited an inward current response. The amplitude of the oxytocin-induced current increased with increasing dose of oxytocin, but no current was elicited following stimulation with vasopressin. The oxytocin-induced current was completely eliminated as a result of pretreatment with a specific oxytocin antagonist. 21 of 27 oocytes injected with term myometrial mRNA showed a large amplitude (77.0 +/- 16.1 nA) reaction to oxytocin. In comparison, only 3 of 13 oocytes injected with early gestational myometrial mRNA exhibited a small amplitude (4.6 +/- 1.4 nA) reaction to oxytocin. No oxytocin response was observed in oocytes injected with non-pregnant myometrial mRNA. These results indicate that the striking increment in oxytocin sensitivity in term uterus depends on the increase in mRNA encoding oxytocin receptors.

Animals↗

PubMed1992

The fetus as an allograft: immunobiologic role of human trophoblasts for fetal survival.

OBJECTIVE: The hypothesis of this study is that trophoblasts contribute to the survival of the mammalian fetal allograft. STUDY DESIGN: Immunologic and molecular biologic studies were performed with human trophoblasts or trophoblastic tumor cells to investigate the expression of class I human leukocyte antigens, the susceptibility to natural killer and lymphokine-activated cells, the ontogeny of Fc gamma-receptors, and the production of immunosuppressive factors. RESULTS: Heterogeneous expression of class I human leukocyte antigens on trophoblasts was regulated at transcriptional level. Trophoblasts showed low susceptibility to natural killer and lymphokine-activated cells. Trophoblasts expressed natural killer cell-type Fc gamma-receptor III, which mediates phagocytosis. The trophoblast-derived immunosuppressive factor was very similar to transforming growth factor-beta. CONCLUSION: The trophoblasts, which ultimately form the fetoplacental interface, constitute a major immune barrier for the survival of the allogenic conceptus.

Female↗

PubMed1992

Interleukin-8 in cord sera: a sensitive and specific marker for the detection of preterm chorioamnionitis.

Interleukin-8 (IL-8) exerts chemotactic activity on neutrophils at inflammatory sites to eliminate invading bacteria. To investigate whether the preterm fetus with chorioamnionitis produces IL-8, the titers of IL-8 were examined in sera of babies with (n = 38) and without chorioamnionitis (n = 34) using an EIA kit specific for IL-8. The infected babies had a significantly higher IL-8 titer than those not infected at 22-36 gestational weeks. The IL-8 titer was increased even in the mild histologic stage of chorioamnionitis and became much higher in the more severe stage. The IL-8 elevation, however, was remarkably suppressed by infusion of a steroid into the mother to promote fetal lung maturation. This retrospective study demonstrated that titration of IL-8 in cord serum is a more useful marker for the early detection of chorioamnionitis, because of its higher sensitivity and specificity, than conventional markers such as C-reactive protein.

Anti-Bacterial Agents↗

PubMed1992

Human placenta constitutively produces interleukin-8 during pregnancy and enhances its production in intrauterine infection.

Interleukin-8 (IL-8) exerts unique chemotactic and activating activity on neutrophils. To address the significance of IL-8 in the fetoplacental unit during pregnancy, we cultured human placental explants that had been obtained by vaginal delivery, Caesarean section, or artificial abortion and then measured the IL-8 titer in the culture supernatants by enzyme immunoassay (EIA). Chorionic tissue from the first trimester produced a significant amount of IL-8 (2.2 +/- 0.4 ng/ml/10 mg, n = 5), while placentae in the second trimester (8.3 +/- 1.6 ng/ml/10 mg, n = 7) or at term (9.2 +/- 0.7 ng/ml/10 mg, n = 29) produced significantly higher amounts of IL-8. The presence or absence of labor did not affect the amount of placental IL-8 production. However, placentae with chorioamnionitis (25.2 +/- 1.6 ng/ml/10 mg, n = 9) showed significantly higher IL-8 production than those without chorioamnionitis (p less than 0.0001). Northern blot analysis of IL-8 mRNA expression demonstrated a constant level during pregnancy with or without chorioamnionitis, indicating the possibility that the major site of regulation of IL-8 synthesis in the placenta is posttranscriptional. Immunohistochemical analysis of first and third trimester placental tissues with rabbit anti-IL-8 antibody revealed the IL-8 producing cells to be trophoblasts and macrophage-like cells. IL-8 produced by the placental cells might contribute to potentiation of the immunocompetence of placental cells against bacteria invading the fetoplacental unit.

Blotting, Northern↗

PubMed1992

Tumor necrosis factor-alpha inhibits human chorionic gonadotropin secretion.

The placenta is a major source of tumor necrosis factor-alpha (TNF alpha) and is rich in TNF alpha receptors. TNF alpha inhibited hCG secretion by normal chorionic villi at 6 weeks gestation, but chorionic villi contain the heterogenous cell population. To investigate the direct effects of TNF alpha on trophoblasts, the NUC1 choriocarcinoma cell line was used as an in vitro placental cell model. TNF alpha also inhibited hCG secretion by NUC1 cells at concentrations from 1-100 U/mL. TNF alpha at concentrations of 1, 10, and 100 U/mL significantly decreased hCG secretion for 24 h to 88%, 81%, and 71% of the control level, respectively. The expression of hCG beta mRNA was also decreased to 23% of the control level after 24 h of TNF alpha treatment (100 U/mL). Inhibition occurred after 12 h of TNF alpha treatment (100 U/mL). Two measurements, trypan blue dye exclusion and 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide reduction, revealed that these inhibitory effects were not due to the cytotoxic activity of TNF alpha on NUC1. In conclusion, TNF alpha reduces hCG secretion in vitro.

Blotting, Northern↗

PubMed1992

Trophoblast-derived tumor necrosis factor-alpha induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6-receptor-dependent system in the normal human trophoblasts.

The titer of tumor necrosis factor-alpha (TNF alpha) secreted by placental blocks was determined by enzyme immunoassay. The source of placental TNF alpha was immunohistochemically demonstrated with monoclonal anti-TNF alpha antibody to be only trophoblasts. Purified trophoblasts produced 174.4 ng/L TNF alpha by 24 h of culture in vitro. To investigate the role of TNF alpha in placental hormonogenesis, purified trophoblasts were stimulated with recombinant TNF alpha (rTNF alpha) to determine the hCG titer by enzyme immunoassay. Trophoblasts stimulated with rTNF alpha released hCG in a dose-dependent fashion with kinetics similar to those of recombinant interleukin-1 (rIL-1)-stimulated trophoblasts. The stimulated trophoblasts released IL-6 before hCG, but failed to show hCG release when pretreated with anti-IL-6 receptor (anti-IL-6-R) monoclonal antibody PM-1. However, the pretreatment of trophoblasts with PM-1 did not interfere with rTNF alpha-induced IL-6 release, ruling out the possibility of a nonspecific toxic effect of PM-1 on trophoblasts. These results suggest that trophoblast-derived TNF alpha induced IL-6 release and then activated the IL-6-R system in trophoblasts to release hCG. Since IL-1 has also been demonstrated to induce similar release of IL-6 and hCG from trophoblasts, the effects of TNF alpha and IL-1 on these trophoblast functions were also examined. Simultaneous stimulation of trophoblasts with rTNF alpha and gamma IL-1 alpha resulted in synergistic enhancement of IL-6 release, subsequently leading to enhanced hCG release. Collectively, trophoblast-derived TNF alpha and IL-1 synergistically regulated the level of IL-6 secreted by trophoblasts, the magnitude of which determined the level of hCG released by activating the IL-6-R system in trophoblasts.

Antibodies, Monoclonal↗

PubMed1992

Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts.

Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.

Chorionic Gonadotropin↗

PubMed1992

Interleukin-1 (IL-1)-induced IL-6- and IL-6-receptor-mediated release of human chorionic gonadotropin by choriocarcinoma cell lines (Jar and HCCM-5) activates adenosine 3',5'-monophosphate-independent signal transduction pathway.

The status of preservation of the ability to secrete cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and IL-6, and the cytokine-mediated regulatory cascade was investigated in four choriocarcinoma cell lines. Each cell line constitutively produced IL-6, but not IL-1 alpha, IL-1 beta, or TNF alpha. Jar and HCCM-5 cells responded to IL-6, releasing hCG by direct activation of IL-6 receptors (IL-6-R) with IL-6. Both cell lines also responded to IL-1, but failed to responded to TNF alpha. When stimulated with recombinant IL-1 alpha, both cell lines released IL-6 and activated the IL-6-R system to release hCG, whereas stimulation with TNF alpha failed to release hCG. The experiments showed that both the Jar and HCCM-5 cell lines possessed a partially intact cytokine-mediated cascade, suggesting that IL-1-induced IL-6 release and IL-6-R activation operate in an autocrine manner. In contrast, NUC-1 and SCH cells failed to respond to IL-6, IL-1, or TNF alpha. Although 8-bromo-cAMP, which is a cAMP analog, stimulates hCG release by Jar cells, it failed to stimulate IL-6 release. Moreover, cAMP-mediated hCG release was not blocked by PM1, an anti-IL-6-R antibody. This suggests that elevation of the cytoplasmic cAMP level might activate a pathway different from the IL-6- and IL-6-R-dependent pathway. Moreover, IL-1- and IL-6-mediated hCG release was not blocked by H8, a cAMP-dependent kinase inhibitor, which further suggests that the IL-1- and IL-6-mediated pathway functions independently of the cAMP-dependent pathway in releasing hCG in Jar cells.

8-Bromo Cyclic Adenosine Monophosphate↗