Human Chorionic Gonadotropin Production Research Articles

In-vitro secretion of prostanoids by placental villous cytotrophoblasts in pre-eclampsia

Villous trophoblasts isolated from term placentae of normal pregnancies, and pregnancies complicated by chronic hypertension or pre-eclampsia, were examined over 7 days in primary culture. Low levels of prostaglandin E2 and prostacyclin (measured as 6-keto prostaglandin Flα) were secreted by trophoblast cells from all three clinical groups. Secretion was maximal at day 1 and decreased exponentially thereafter. Thromboxane secretion also fell sequentially from day 1. Thromboxane secretion by pre-eclampsic trophoblasts was three to four times that of cells from normal or chronically hypertensive subjects. Prostanoid secretion by isolated cultured cytotrophoblasts was not dependent on aggregation or morphological alteration, nor related to changes in progesterone or human chorionic gonadotrophin production. Because the local maternal circulation is exposed to substances secreted by this cell population, thromboxane could be the trigger for vasoconstriction and coagulation found within the maternal uteroplacental circulation in pre-eclampsia.

Ectopic hormone production by ovarian neoplasms

Ovarian neoplasms, producing ectopic hormones, other than struma ovarii, are extremely rare. We review such tumors that have been reported in the world9s literature during the last 15 years. Most patients presented with a clinical picture which was typical of the excess hormone produced. The clinical syndromes associated with ovarian neoplasms are: the Zollinger-Ellison syndrome, hypoglycemia, hyperthyroidism, hypercalcemia, Cushing9s syndrome, hyperprolactinemia, hypertension related to renin or aldosterone production, and ectopic production of human chorionic gonadotropin. The clinical characteristics of these patients, as well as the pathologic findings, are described. In most of these cases the tumor was not localized preoperatively and the patients underwent unnecessary extensive operative procedures. Regardless of benign or malignant histology, complete excision of the tumor practically offers cure to these patients. Although rare, the possibility of ectopic hormone production by ovarian neoplasms should be kept in mind when investigating a patient with a nonlocalized hormone-secreting tumor. A review of ovarian neoplasms producing ectopic hormones is herein presented along with the diagnostic and therapeutic dilemmas characterizing this entity.

Molecular interactions during pregnancy

Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein (Ad4BP), is a recently-described transcription factor, which has been shown to be important for the differentiation of steroidogenic tissues. In addition, SF-1 has been implicated in regulating the glycoprotein hormone alpha-subunit gene in a pituitary gonadotroph cell line. Considering that the human placenta produces both steroids and human chorionic gonadotrophin (HCG), we studied the expression of SF-1 in this tissue. Human first trimester and term placentas were collected at the time of therapeutic abortion and birth respectively. Messenger RNA was extracted, reverse transcribed, and used for polymerase chain reaction (PCR) amplification with primers specific for the human SF-1 cDNA sequence. A band of the expected size was obtained from both first and third trimester samples, indicating that SF-1 expression in the human placenta starts early in pregnancy and is maintained until birth. In addition to normal placental samples, JEG3 and JAR choriocarcinoma cells were also analysed and found to express SF-1 mRNA. The identity of the amplified products was confirmed by diagnostic restriction digest and Southern hybridization. SF-1 protein was localized mainly to the nuclei of the cyto- and syncytiotrophoblast and to some mesenchymal villous nuclei by immunocytochemistry using a specific antibody. We conclude that SF-1 is expressed in human first trimester and term placenta, where it could be implicated in the regulation of HCG production, in steroidogenesis, or both.

Soluble interleukin-6 (IL-6) receptor in the sera of pregnant women forms a complex with IL-6 and augments human chorionic gonadotropin production by normal human trophoblasts through binding to the IL-6 signal transducer

Soluble interleukin-6 (IL-6) receptor in the sera of pregnant women forms a complex with IL-6 and augments human chorionic gonadotropin production by normal human trophoblasts through binding to the IL-6 signal transducer

Comparative regulation of inhibin, activin and human chorionic gonadotropin production by placental trophoblast cells in culture

International Journal of Gynecology & ObstetricsVolume 50, Issue 3 p. 322-322 Citations from the literature (including the russian literature) experimental medicine Comparative regulation of inhibin, activin and human chorionic gonadotropin production by placental trophoblast cells in culture Keelan J.; Song Y.; France J.T. NZL Placenta 1994 15/8 (803–818) First published: September 1995 https://doi.org/10.1016/0020-7292(95)92806-CAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume50, Issue3September 1995Pages 322-322 RelatedInformation

Placental production of human chorionic gonadotrophin α and β subunits in early pregnancy as evidenced in fluid from the exocoelomic cavity

Cavernous nerves (CNs) injury is the main cause of erectile dysfunction (ED) following radical prostatectomy. Its restoration remains challenging.To investigate the feasibility of erectile function recovery by autologous vein graft after bilateral CNs being excised in a rat model.A total of 36 adult male Sprague-Dawley rats were randomized into three groups. A 5 mm segment of CN was excised bilaterally in group B and C. In group B, a 7-mm segment of autologous saphenous vein was interposed at the defect site bilaterally, with two nerve stumps inserted into the vein lumen. Group C underwent no repair. Group A was accepted a sham operation. 4 months later, apomorphine tests were performed on each rat, followed by injection of 4% fluorogold into bilateral corpus cavernous. 5 days later, after monitoring intracorporal pressure (ICP) changes induced by electrostimulation of CN, rats were sacrificed and their bilateral major pelvic ganglions were obtained for detection of fluorogold, and penile tissues of middle shaft were obtained for detecting nitric oxide synthase-containing nerve fibers in penile dorsal nerves.Erectile function was assessed by apomorphine test and ICP monitoring. CN regeneration was judged by fluoroglod tracing and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining.Apomorphine tests resulted in 58% rats with erectile responses in group B, whereas no erection was observed in group C. ICP monitoring also demonstrated a significant recovery in erectile function in group B compared with group C. Much more and brighter fluorogold coloring cells were examined in major pelvic ganglions of group B than those of group C. NADPH-diaphorase staining also showed much more positive fibers were detected in penile dorsal nerves in group B than in group C.Autologous vein graft could provide a guide channel to induce CN regeneration and successfully restore autonomic erectile function after CNs being excised in rats. Hu W, Cheng B, Liu T, Li S, and Tian Y. Erectile function restoration after repair of excised cavernous nerves by autologous vein graft in rats.

Cellular adaptation to chronic cadmium exposure: intracellular localization of metallothionein protein in human trophoblast cells (JAr).

Trophoblast cells are the first embryonic cells that modulate the transfer of a variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal to the fetal circulation in the human placenta. Human placental exposure to the toxic metal, cadmium (Cd) results in a decrease in the production of human chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to adapt to exposure to the toxic metal Cd has been considered crucial. In this study, the expression and intracellular localization of metallothionein (MT), a small molecular weight, metal binding protein, was examined in trophoblast cells (JAr) grown in normal media and in cells exposed chronically (6 months) to 2 microM CdCl2. Conventional and confocal fluorescence microscopy were used to examine the intracellular localization of MT protein in control cells and cells grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily perinuclear with low level, punctate expression in the cytosol. Following both chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3-fold in both chronic and acute exposures) and the protein was now concentrated inside the nucleus with a lacy, cytoskeletal pattern of expression in the cytosol. To determine if the nuclear accumulation of MT protein was dependent on new protein synthesis, control cells were exposed to CdCl2 (2 microM) and cycloheximide (2 micrograms/. ml) for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukemia inhibitory factor: A significant modulator of human chorionic gonadotropin production in first trimester human cytotrophoblasts

Leukemia inhibitory factor: A significant modulator of human chorionic gonadotropin production in first trimester human cytotrophoblasts

Comparative regulation of inhibin, activin and human chorionic gonadotropin production by placental trophoblast cells in culture

In the present study, we investigated the roles of cyclic adenosine monophosphate (cAMP), intracellular calcium, glucocorticoids, protein kinase-C and gonadotrophin-releasing hormone (GnRH) in regulating human chorionic gonadotrophin (hCG), inhibin and activin production in cultured human term placental trophoblast cells. Inhibin and hCG were measured in conditioned media by radioimmunoassay, while putative forms of inhibin and activin were characterized by western blotting using affinity-purified antisera directed against the inhibin alpha- and beta A-subunits. Inhibin and hCG secretion were stimulated by dexamethasone (0.2 microM), GnRH (5-25 microM), calcium ionophore A23187 (0.2-1 microM), phorbol-12-myristate-13-acetate (22 nM) and epinephrine (1 microM), with increasing response over successive 24-h treatment periods. Two molecules Mr approximately 30 and 32 kDa appeared to be the predominant dimeric forms of inhibin secreted by the cells, while 26 kDa activin was present in excess over inhibin. Large amounts of 40-44 kDa protein were detected by the alpha-directed antisera only, which may be a form of the inhibin alpha-subunit precursor protein. Secretion of activin was responsive to phorbol ester-mediated stimulation but not to the presence of GnRH or elevated cAMP concentrations. The divergence in maternal serum inhibin and hCG concentrations during late pregnancy remains unexplained by these findings.

The placental transfer and toxicity of selenite relative to cadmium in the human term perfused placenta

Selenite and cadmium both cause reproductive effects in animals. Cadmium is an acute placental toxicant, with apparent limited transfer to the fetus. This study examines the placental transfer of selenite, and the hypothesis that similar to cadmium, selenite may also be a direct placental toxicant. Using dual perfusion of the human term placental lobule, both non-protein bound (< 776 Da) selenite and cadmium equilibrated across the placenta within 4 h. The transfer of selenium, added as selenite, was not limited at concentrations from 2-40 nmol/ml. At initial maternal concentrations of 20 nmol/ml, selenium attained higher concentrations in the fetal perfusate compared with cadmium concentrations. Protein binding of cadmium in perfusates (45 per cent at 30 min) and placental cytosol (approx. 87 per cent) was greater than selenium (perfusate, 7 per cent at 30 min, cytosol, 50-60 per cent), which may partially account for the differences in placental transfer. Cadmium (20 nmol/ml) produced adverse effects on the production and release of human chorionic gonadotropin (hCG) in 4 h. No adverse effects were noted during 4 h exposures to selenite at initial concentrations of up to 40 nmol/ml. Thus, unlike cadmium, in which placental accumulation and direct placental toxicity contributed to acute reproductive effects, selenite at concentrations up to 40 nmol/ml was not a direct toxicant under these perfusion conditions.

Fertilization and early embryology: Embryonic human chorionic gonadotrophin secretion and hatching: poor correlation with cleavage rate and morphological assessment during preimplantation development in vitro

Of 593 bipronucleate eggs allowed to develop in vitro, 275 (46%) achieved the blastocyst stage and beyond, 124 (21%) initiated hatching, but only 49 (8%) fully hatched. About half of the pre-embryos (48%) which developed to these more advanced stages were incapable of secreting significant amounts (> 200 microIU) of cumulative human chorionic gonadotropin (HCG) up to day 14. HCG production does not appear to begin until the expanded stage and is independent of hatching. Assessing cleavage rate through successive stages and morphological grades up to the 8-cell stage had little bearing on the ability of a pre-embryo to hatch or secrete HCG. Progression through the stages of preimplantation development in vitro does not always appear to be accompanied by the necessary biochemical stages. If only 46% of pre-embryos with two pronuclei are capable of achieving the blastocyst stage, and of these only 52% are capable of secreting HCG, then it follows that only 24% of the original bipronucleate pre-embryos in vitro can be considered anatomically and biochemically competent. However, this is only applicable for pre-embryos not transferred or frozen, and is thus subject to a selection bias. Inability to detect HCG in vitro is not conclusive proof that a pre-embryo is developmentally incompetent. Similarly failure to hatch in vitro may not be taken as definitive evidence that hatching would have failed had fertilization and development been completed in vivo. Nevertheless, if pre-embryonic development in vitro is similar to that in vivo, this may be a contributory factor in the low pregnancy rates following in-vitro fertilization treatment.

Placental production of human chorionic gonadotrophin α and β subunits in early pregnancy as evidenced in fluid from the exocoelomic cavity

Levels of human chorionic gonadotrophin (hCG) and of its free alpha and beta subunits were measured using specific immunoradiometric assays in exocoelomic fluid (ECF) and maternal serum (MS) collected from five pregnant women at 6.6-8 weeks of gestation. Mean levels of hCG and its free subunits were significantly (P < 0.001) higher in ECF than in MS: 3.5-fold for hCG, 600-fold for free alpha hCG and 38-fold for beta hCG. There was no correlation between either hCG levels or levels of its free subunits in ECF and MS. On a molar basis, the quantity of free alpha hCG subunit expressed as a percentage of the total (free+combined) amount was 83% in ECF and 2.7% in MS (P < 0.001). The amount of free beta hCG subunit as a percentage of the total was 22% in ECF and 3.5% in MS (P < 0.001). The ratio of the total amounts of alpha- and beta hCG subunits amounted to 4.6 in ECF and 0.99 in MS (P < 0.001). The heterogeneity of hCG was further investigated by polyacrylamide gel electrophoresis followed by immunoblotting. Several bands with molecular mass ranging from 42 to 57 kDa, corresponding to hCG dimers, were immunodetected in ECF and MS with anti-alpha hCG and anti-beta hCG monoclonal antibodies. A free 35 kDa beta hCG immunoreactive band was found in ECF and MS. A free alpha hCG immunoreactive band was observed at 23 kDa in ECF and at 21 kDa in MS. These findings suggest that the exocoelomic cavity is a reservoir where hCG and its subunits produced by trophoblast accumulate directly.(ABSTRACT TRUNCATED AT 250 WORDS)

Eutopic production of human chorionic gonadotropin β (hCGβ) and luteinizing hormone β (hLHβ) in the human testis

The classical pregnancy and tumor marker hCG has long been considered to be only accidentally expressed ectopically, e.g. by tumors. The biological functions of low levels of bCGβ, hCGα and holo-hCG in the sera of nonpregnant healthy individuals remained unclear. Immunological analyses by our ultrasensitive time-resolved fluoroimmunoassays revealed a concentration gradient from < 5 pg hCG β ml in cubital vein serum versus up to 480 pg hCG β ml in the corresponding benign testicular hydrocele fluids. Moreover, hCGβ and its cognate molecule luteinizing hormone β (LHβ) were present in cytosolic extracts of normal human testes. Both hCGβ and hLHβ are eutopically produced as proven by RT-PCR and subsequent Southern and dot blot analyses. Thus, the view of a purely systemic hormonal function of hLH, and of hCG during pregnancy needs a reassessement as hCGβ and hLHβ are synthesized in the human testis and autocrine/paracrine actions seem to be likely.

Ectopic human chorionic gonadotrophin (HCG) production: is the detection by serum analysis of HCG of clinical relevance in transitional cell carcinoma of the bladder?

To assess the potential value of ectopic beta-human chorionic gonadotrophin (beta HCG) measurement in the clinical management of transitional cell carcinoma (TCC). A prospective serological study of 163 consecutive patients undergoing cystoscopy as new or review cases was performed to assess any correlation between beta HCG production and histological grading or stage. Ten per cent of patients with TCC had a raised beta HCG level but there was no correlation with tumour differentiation, staging or prognosis. beta HCG has no role as a tumour marker for TCC and therefore appears unlikely to play a part in the clinical management or treatment of urothelial tumours.

The effects of cytokines on human chorionic gonadotropin (hCG) production by a trophoblast cell line

The present study was conducted to investigate the effects of cytokines on human chorionic gonadotropin (hCG) and its alpha- and beta-subunit release as well as protein synthesis in a trophoblast cell line. The human choriocarcinoma cell line, Jar, was used as a trophoblast model. Jar cells were incubated for 24 h with varying concentrations (5 × 10 −4 −40 μg/ ml) of the following cytokines: I1-1, I1–2, I1–3, I1–4, I1–5, I1–6, IFN-gamma, tumor necrosis factor (TNF)-alpha, M-CSF and GM-CSF. Supernatants were assayed for hCG and its alpha- and beta-subunits by immunoradiometric methods. Cytotoxic effects were assessed by trypan blue staining. Protein synthesis was measured by [ 3H]leucine incorporation. The cytokines I1-1 and TNF-alpha significantly stimulated hCG release. The other cytokines had no significant effect on hCG production. Protein synthesis by the Jar cells was not significantly affected by either I1-1 or TNF-alpha. However, IFN-gamma (40 μg/ml) significantly suppressed protein synthesis by the Jar cells. Trophoblast viability in the presence of TNF-alpha (10 μg/ml) and IFN-gamma (40 μg/ml) was only 40% and 50%, respectively. These results suggest that cytokines may be important regulators of trophoblast function. I1-1 appears to have a stimulatory effect on trophoblast hCG release, while TNF-alpha and IFN-gamma appear to have cytotoxic effects on trophoblast cells.

Norepinephrine regulates human chorionic gonadotrophin production by first trimester trophoblast tissue in vitro

The effect of norepinephrine (NE) upon human chorionic gonadotrophin (hCG) production by 6-8 week gestation placental explants has been investigated. NE (5 micrograms/ml) enhanced hCG secretion significantly from the second day of treatment. The stimulatory effect of NE on hCG secretion could be abolished by the alpha 1-receptor specific antagonist prazosin (10(-4) M) and partly diminished by the beta 1-receptor specific antagonist atenolol (10(-4) M), but was not influenced by the alpha 2-receptor specific antagonist yohimbine (10(-4) M). The involvement of the alpha-receptor in the regulation of hCG secretion was further confirmed by addition of the alpha-receptor agonist clonidine (10(-6) M) which had a similar stimulatory effect on hCG release but the effect was antagonized by both prazosin and yohimbine. Further study showed that NE induced a significant increase in cyclic adenosine monophosphate (cAMP) production by trophoblast tissue. Cyclic AMP secretion in the NE-treated group was fivefold higher than that of the control group. Both the protein kinase C (PKC) specific activator 1-deoyl-2-acetyl-sn-glycerol (OAG) and the PKC non-specific activator phorbol-12-myristate-13-acetate (PMA) had a stimulatory effect on hCG secretion, while the PKC inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H7) diminished the hCG secretion stimulated by NE. The effect of NE was blocked by the voltage-dependent calcium channel blocker nifedipine but not by the voltage-independent calcium channel blocker gadolinium chloride (GdCl3). On the other hand, anti-gonadotrophin releasing hormone (GnRH) IgG and the GnRH antagonist (D-Phe2, D-Trp6)-GnRH did not influence the stimulatory effect of NE on hCG release. The results indicate that NE regulates hCG production in human first trimester trophoblast tissue. The effect of NE was mainly mediated by alpha 1 and partly by beta 1 receptors. Cyclic AMP, the PKC signal transduction pathway and the voltage-dependent calcium channels were involved in NE action.

Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy

Purpose : To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonatropin values treated with radiotherapy were analyzed. Methods and Materials : The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadtropin were found: 96 Stage I, 20 II A, 7 II B, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1–12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 II A, 5 II B and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also intial (3 Stage II B 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts). Results : The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group ( p < 0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 II B, 3 III and 1 IV). Of these, there were one infield recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotropin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage II A and 65% for Stage II B and III [ p < 0.001 between I and II B + III, p < 0.05 between II A and II B + III]). Four of the 7 recurrences were salvaged by chimiotherapy ± radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group ( p = 0.10). Conclusion : Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and II A seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low.

Fertilization and early embryology: Human chorionic gonadotrophin: embryonic secretion is a time-dependent phenomenon

Of 48 spare human pre-embryos achieving the expanded blastocyst stage, 22 (45.6%) secreted significant amounts of human chorionic gonadotrophin (HCG) (> 5 IU/l/day). Of these, nine remained intrazonal, seven partially hatched and six fully hatched. Embryonic production of HCG in vitro appeared to be time-dependent, starting after a certain minimum time (approximately 160 h post-insemination) and rising exponentially, with maximal HCG production around day 10. Hatching was not a prerequisite for HCG secretion, since similar amounts were produced by intrazonal blastocysts. Blastocysts derived from abnormally fertilized oocytes also began secreting HCG exponentially but secretion was delayed and the upper limit of maximum HCG secretion rate was comparatively low. The actual amount of HCG is thought to reflect the number of viable trophectoderm cells producing the hormone. HCG doubling times for blastocysts in vitro were rapid when compared to implanting blastocysts of a similar age in vivo, with 19/22 (86.4%) blastocysts having a doubling time of < 10 h. Provided a pre-embryo can secrete HCG and maintain an adequate doubling time, sufficient HCG should be produced for initial stages of embryonic recognition in vivo. Since intrazonal blastocysts are capable of fulfilling both of these criteria, the limiting factor in realizing their full potential may be escaping from the zona pellucida.

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

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

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.