Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo.

Tyrosine kinase inhibitors (TKIs) have emerged as a promising class of agents against thyroid cancer. The aim of the present study was to investigate the in vitro and in vivo activity of dasatinib against a panel of thyroid cancer cell lines and explore possible mechanisms of action, using various assays and western blotting. Our results showed that dasatinib exhibits prominent cytostatic activity both in vitro and in vivo against thyroid cancer cell lines with RET/PTC rearrangement (BHP2-7) and KRAS mutation (Cal62). Although dasatinib has primarily been described as an ABL/SRCfamily kinase inhibitor, the cytostatic activity observed in the present study is mediated by several off-target effects of dasatinib, some of which have not previously been reported. These effects include a reduction in phospho-FAK, FAK, RAS, Caveolin and SYK protein levels and an increase in ß-catenin protein expression, which leads to the induction of senescence, an increase in the adhesiveness of the cells, a decrease in reactive oxygen species level, and changes in the expression profile of molecules involved in cellular adhesion such as integrins. Therefore, we propose that dasatinib is an effective therapeutic agent for certain patients with thyroid cancer, and these candidate patients may be identifiable on the basis of standard genotypic analyses.

Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells.

Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor (TSHR). Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 beta (HNF3 beta)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein (C/EBP beta). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed decreased expression of HNF3 beta/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3 beta/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBP beta was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBP beta in the cytoplasm, suggesting that a large proportion of C/EBP beta protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cells.

Testosterone patches in the management of patients with mild/moderate systemic lupus erythematosus.

OBJECTIVES: Androgen deficiency has been associated with the development of systemic lupus erythematosus (SLE). The aim of this study was to test the efficacy of testosterone patches vs placebo in female SLE patients with baseline mild-to-moderate disease activity in a randomized, double-blind, single-centre placebo-controlled trial. METHODS: Patients received testosterone (150 microg) or placebo transdermal patches for 12 weeks. Patients were assessed at 4-weekly intervals for disease activity using the Safety of Oestrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), Systemic Lupus Activity Measure-Revised (SLAM-R) and The British Isles Lupus Assessment Group (BILAG) indices, physician global assessment (PGA), quality of life using the SF-36 survey and sexual functioning using the Derogatis score. Data were analysed using two sample t-tests to compare the mean difference from baseline to week 12 in the testosterone patch and placebo groups. RESULTS: Thirty-four patients were recruited in to each group. There was no significant baseline difference between the groups in age, race or marital status. There was no significant difference between treatment groups in the mean change in SELENA-SLEDAI (0.547 +/- 3.72, P > 0.60), nor in PGA or BILAG system scores. The mean change in SLAM-R score was statistically different (2.06, S.D. 3.3, P = 0.01) but was not considered clinically meaningful. Health transition also showed a small change (P < 0.03). There was no significant difference in the Derogatis scores or toxicity. CONCLUSIONS: Testosterone patches were safe but did not significantly affect disease activity, quality of life or sexual functioning. Increased use of steroids in the placebo group may have confounded the study results.

A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma.

Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.

Treatment of gynecomastia.

Gynecomastia is a common problem during puberty as well as later adulthood, and is caused by hormonal imbalance at the breast tissue level. Various medications and medical conditions can cause gynecomastia and when the drug is discontinued or medical condition cured, it will frequently resolve. Medical therapy can be tried for patients with persistent gynecomastia associated-tenderness or social embarrassment prior to contemplating surgical removal of the breast tissue.

Reevaluation of the impact of a stringent low-iodine diet on ablation rates in radioiodine treatment of thyroid carcinoma.

Prior analyses of the impact of stringent, preablative low-iodine diets (LIDs) on ablation in patients with differentiated thyroid cancer postthyroidectomy are dated. We retrospectively reviewed first-time, short-term ablation rates for 44 LID patients and 50 patients following a regular diet (RD) who were verbally instructed to avoid salt, seafood, and multivitamins containing iodine. Patients who had undergone ablation were given between 100 and 200 mCi of 131I, depending on the presence of metastases. We found a 68.2% ablation rate for LID patients, compared to a 62.0% rate for RD patients, a nonsignificant difference (p = 0.53). We observed a dose-response relationship for both patient groups, with higher ablation rates corresponding to higher doses of radioiodine administered. We also measured iodine levels in spot urine samples from 7 matched LID patients and 7 matched RD adherents (healthy volunteers) prediet and postdiet as well as 39 healthy volunteers. LID patients had a lower mean urinary iodine level postdiet (173.9 microg/L; range, 45-1,217 microg/L; standard deviation [SD] = 127.7) than the RD patients (mean, 381.4 microg/L; range, 140-630 microg/L; SD = 196.3) or the 39 normal controls (444.0 microg/L; range, 50-1,690 microg/L; SD = 413.4). Whereas the LID lowered urinary iodine levels by 69.4% from prediet values, the RD reduced urinary iodine by 23.6%. Although differences in the reduction of urinary iodine levels between the LID and the RD were substantial, both groups experienced equivalent outcomes. The level of iodine in the American diet has progressively decreased, and may be much lower now than when prior LID studies were conducted. We suggest that prescribing a refined, less stringent diet that avoids high-iodine-containing foods would offer equivalent outcomes with increased patient convenience.

The nonimpact of thyroid stunning: remnant ablation rates in 131I-scanned and nonscanned individuals.

Thyroid stunning has been reported as the temporary impairment of thyroid tissue after a 111-MBq or greater diagnostic 131I dose that decreases the final absorbed dose in ablative therapy. Concerns regarding the reality of stunning have arisen in part due to a flawed study design in prior reports. To assess whether a stunning effect has any impact on therapeutic outcomes, we compared initial treatment ablation rates in patients who received 111- to 185-MBq 131I diagnostic scans (n = 37) before ablative doses of 3700-7400 MBq with ablation rates in patients who did not receive any 131I before the initial treatment dose (n = 63). Ablation rates were 64.9% for scanned patients and 66.7% for nonscanned patients, a nonsignificant difference. Nonscanned patients with metastatic lesions (n = 23) were ablated at a higher rate (78.3%) than scanned patients (n = 9) (66.7%), but the difference was not significant (P = 0.50). It is possible that the reported stunning phenomenon, specifically its impact in temporarily impairing tissue, has been overemphasized.

The value of a hospitalist service: efficient care for the aging population?

BACKGROUND: We studied patients of a hospitalist teaching service and patients receiving routine private care (control subjects). We sought to evaluate whether inpatients cared for by an academic hospitalist service had lower lengths of stay and resource utilization rates. METHODS: Using monthly hospital census data, 477 hospitalist cases and 1,160 control cases were selected by explicit criteria from the Medicaid population of a large, university-affiliated, community medical center between July 1, 1996, and June 30, 1997. Outcomes in hospitalist faculty patients were compared to those of control patients under the care of private providers. RESULTS: Median length of stay was 4 days for control subjects and 3 days for the hospitalist service (p < 0.0001). Median total cost per case was $4,853 for control subjects and $4,002 for hospitalist patients (p < 0.0001). Only patients > or = 65 years old showed statistically significant reductions in both length of stay (p < 0.0001) and total cost (p = 0.002). Subspecialty consultation rates were 37.6% for control subjects and 16.6% for hospitalist cases (p < 0.0001). We noted increasing consultations for patients > or = 65 years old, especially in the control group (p = 0.001). No significant differences in mortality, 30-day readmissions, or interfacility transfers were observed. CONCLUSIONS: Patients cared for by an academic hospitalist service that includes actively participating medical residents appear to have lower lengths of stay, total costs, and consultation rates than patients receiving routine private care. The reductions are largely observed among patients > or = 65 years old.

Accuracy considerations when using early (four- or six-hour) radioactive iodine uptake to predict twenty-four-hour values for radioactive iodine dosage in the treatment of Graves' disease.

Although literature has offered methods to predict 24-hour radioactive iodine uptake values from early (4- to 6-hour) measurements, the resultant dosage errors have not been examined. Potential errors include underdosage, overdosage, and a failure to recognize rapid turnover patients (early-to-late uptake ratios > or = 1) who are at high risk for treatment failure and full-body radiation exposure. We developed and tested a novel method for minimizing error involved in using a single early uptake measurement to derive late uptake. From a retrospective analysis of 203 Graves' disease patients, receiver operating characteristic (ROC) curve analysis enabled us to identify patients likely to experience rapid turnover and therefore should receive 24-hour studies. Twenty-four-hour uptake measurements are necessary with 77% or more 4-hour uptake values and 80% or more 6-hour values. After eliminating these patients, we developed linear regression equations to predict the 24-hour uptake from 4-hour (n = 61) and 6-hour (n = 22) rule groups, testing their efficacy on separate 4-hour (n = 61) and 6-hour (n = 21) patient groups. We also used our test population to measure error in four early-to-late uptake conversion formulas presented in the literature. Error involved in these predictions ranged from a 10.6% overestimate for 4-hour calculations to a 5.9% underestimate for 6-hour calculations. When applied to two dosage formulas incorporating gland size, absorbed dose, and 24-hour uptake, average dosage error was 7%. In comparison to the other sources of error radioactive iodine (131I) dosimetry, potential error in predicting 24-hour uptake from 4- or 6-hour uptake values is low.

Transdermal testosterone treatment in women with impaired sexual function after oophorectomy.

BACKGROUND: The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. METHODS: Seventy-five women, 31 to 56 years old, who had undergone oophorectomy and hysterectomy received conjugated equine estrogens (at least 0.625 mg per day orally) and, in random order, placebo, 150 microg of testosterone, and 300 microg of testosterone per day transdermally for 12 weeks each. Outcome measures included scores on the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and a sexual-function diary completed over the telephone. RESULTS: The mean (+/-SD) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter (4.2+/-2.8 pmol per liter) during placebo treatment to 3.9+/-2.4 pg per milliliter (13.5+/-8.3 pmol per liter) and 5.9+/-4.8 pg per milliliter (20.5+/-16.6 pmol per liter) during treatment with 150 and 300 microg of testosterone per day, respectively (normal range, 1.3 to 6.8 pg per milliliter [4.5 to 23.6 pmol per liter]). Despite an appreciable placebo response, the higher testosterone dose resulted in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women (P=0.03 for both comparisons with placebo). At the higher dose the percentages of women who had sexual fantasies, masturbated, or engaged in sexual intercourse at least once a week increased two to three times from base line. The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose (P=0.04, P=0.03, and P=0.04, respectively, for the comparison with placebo), but the scores on the telephone-based diary did not increase significantly. CONCLUSIONS: In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being.

A familial risk profile for osteoporosis.

PURPOSE: To describe genetic epidemiologic aspects of osteoporosis. METHODS: 69 patients with osteoporosis were interviewed regarding personal and family histories of osteoporosis and related fractures. Family history information was obtained on 421 first degree and 748 second degree relatives. RESULTS: 45% of cases reported a family history of osteoporosis. Familial cases were characterized neither by an earlier age of diagnosis nor by a greater degree of phenotypic severity. Empiric risks for osteoporosis were highest for mothers, 33%, and were 19% for sisters. CONCLUSION: These results provide an initial genetic epidemiologic profile for osteoporosis and information useful for genetic counseling.

In vivo and in vitro regulation of thyroid leukemia inhibitory factor (LIF): marker of hypothyroidism.

Several cytokines regulate thyroid function and may be involved in the pathogenesis of thyroid disorders, including euthyroid sick syndrome. Leukemia inhibitory factor (LIF), a neuroimmune pleiotropic cytokine, was measured to assess its role in hypothalamic-pituitary-thyroid function. Mean circulating serum LIF levels in 10 hypothyroid patients [TSH, 23+/-0.5 mIU/L (mean+/-SEM); free T4, 0.77+/-0.1 ng/dL] was 0.29+/-0.04 ng/mL, 145% higher (P < 0.04) than in 20 normal subjects (LIF, 0.20+/-0.02 ng/mL; TSH, 2.23+/-0.21 mIU/L; free T4, 1.23+/-0.04 ng/dL) but was not different from those in 10 hyperthyroid patients (LIF, 0.21+/-0.03 ng/mL; TSH, 0.01+/-0.00 mIU/L; free T4, 3.63+/-0.51 ng/dL). Serum LIF concentrations linearly correlated with serum TSH in the 40 samples (r = 0.58, P < 0.001). When T4 (1-8 microg/kg x day) was administered to cynomolgus monkeys with methimazole-induced hypothyroidism, serum T4 and T3 levels increased appropriately, and TSH and LIF concentrations decreased. When methimazole was given alone, both serum TSH (146+/-30 mIU/L) and LIF (8.84+/-0.49 ng/mL) were markedly induced. When methimazole together with T4 (>2 microg/kg x day) was administered, both serum TSH (7.5+/-1.2 mIU/L) and LIF (6.22+/-0.31 ng/mL) were lowered (P < 0.01). Monkey serum LIF levels and log TSH levels also correlated (r = 0.72, P < 0.01). Cultured thyroid carcinoma cells produced LIF (9.2 ng/10(6) cells/48 h). TSH (100 mIU/mL) and interleukin (IL)-6 (10 nmol/L) stimulated in vitro LIF secretion from the cells by 170+/-12% (P < 0.05) and 261+/-8% (P < 0.05), respectively. Dexamethasone (1 micromol/L) inhibited basal LIF concentration by 83% (P < 0.05), whereas TSH and IL-6 stimulated LIF by 52% (P = 0.04) and 42% (P = 0.03), respectively. However, using Northern blot analysis, we could not observe induction of LIF mRNA by TSH, suggesting that LIF regulation by TSH may be due to stimulation of secretion. The results show that the thyroid gland is a source of LIF production; TSH, IL-6, and glucocorticoid influence thyroid cell LIF expression. The correlation between TSH and LIF suggests that LIF may participate in the physiologic regulation of hypothalamic-pituitary-thyroid function.

Aromatase and gynecomastia.

An imbalance between estrogen action relative to androgen action at the breast tissue level results in gynecomastia. Enhancement of aromatization of androgens to estrogens is important in the pathogenesis of gynecomastia associated with obesity, aging, puberty, liver disease, thyrotoxicosis, 17-oxosteroid reductase deficiency. Klinefelter's syndrome, and neoplasms of the testes, adrenals and liver. A primary aromatase excess syndrome with exuberant gynecomastia had been found both sporadically and in a familial setting. Although aromatase inhibition would appear to be an important class of drugs to treat gynecomastia, relatively little published data with these drugs exist and most concern the use of delta1-testolactone, which reduces the size of the breast glandular tissue, but does not completely ameliorate the problem. Studies with the newer generation of more potent aromatase inhibitors need to be carried out.

Human chorionic gonadotropin production by the pituitary gland in a premenopausal woman.

OBJECTIVE: Our purpose was to investigate the source of human chorionic gonadotropin production in a nonpregnant, premenopausal woman. STUDY DESIGN: A case of human chorionic gonadotropin production by the pituitary gland in a premenopausal woman is described. RESULTS: Our results confirm that a biologically active human chorionic gonadotropin-like molecule was secreted in a nonpregnant woman. CONCLUSIONS: Our results indicate that the pituitary gland was the most likely source of human chorionic gonadotropin production.

Measurement of leukemia inhibitory factor in biological fluids by radioimmunoassay.

Leukemia inhibitory factor (LIF) exhibits multiple biological activities in various tissues, and we have shown that LIF activates POMC gene transcription in response to immune signals. As higher serum levels of LIF have been reported in septicemia, we measured LIF values in biological fluids by RIA. Immunoreactive LIF was detected in 303 of 428 human serum samples. Circulating LIF detection rates were 69% in acute inflammatory diseases, 83% in chronic inflammatory diseases, 61% in noninflammatory diseases, and 90% in cancer patients. Serum concentrations of human LIF was higher in patients with inflammatory disease than in noninflammatory disease (0.80 +/- 0.10 vs. 0.53 +/- 0.02 ng/mL; P < 0.05) or in cancer patients (0.44 +/- 0.06; P < 0.05). Higher serum human LIF levels were found in septicemia (0.78 +/- 0.14 ng/mL), pneumonia (0.80 +/- 0.10 ng/mL), acute bronchitis (0.88 +/- 0.09 ng/mL), other infections (1.01 +/- 0.17 ng/mL), and systemic lupus erythematosus (SLE; 0.79 +/- 0.06 ng/mL). In 7 septicemia patients, Gram-negative infection was associated with higher LIF levels (1.06 +/- 0.16 ng/mL) than was Gram-positive infection (0.58 +/- 0.14 ng/mL). In patients with acute inflammatory disease, serum LIF levels decreased within several days after hospitalization. To test circulating mouse (m) LIF changes in response to inflammatory stress, lipopolysaccharide (LPS) was injected ip to mice. LPS increased serum mLIF values concordantly with ACTH levels. After i.p. injection of 80 microg LPS, serum mLIF increased by 144% (P < 0.05), 173% (P < 0.05), and 134% at 30, 90, and 120 min respectively. In vitro, however, LPS did not increase ACTH and mLIF secretion from dispersed mouse primary pituitary cells. These results suggest that LIF is an important participant in the pathogenesis of the acute inflammatory response. The elevated serum LIF levels observed in inflammation do not appear to originate from the pituitary.

Decidual leukemia inhibitory factor production and action on human chorionic gonadotropin secretion at different stages of gestation in vitro.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine essential for uterine blastocyst implantation. We investigated human LIF production and action on human chorionic gonadotropin (hCG) secretion at different stages of gestation. Decidual and chorionic tissues were obtained at the first and second trimesters of pregnancy, and at term. Decidual and trophoblast cells were isolated and cultured separately and medium LIF or hCG levels were measured by radioimmunoassay. Decidual cells derived from the first and second trimester, and term were cultured for 72 h in serum-containing medium and produced 374 +/- 162 (mean +/- SEM), 140 +/- 14 and 466 +/- 134 ngLIF/mg protein, respectively. Pregnant mare serum gonadotropin (10 U/ml) did not affect LIF production from first-trimester decidual cells, but inhibited second-trimester LIF production to 37% of that of controls (p < 0.05), and stimulated LIF production from term decidual cells to 125% of that of controls (p < 0.05). First-trimester trophoblast cells treated with 10 nmol/l hLIF for 72 h in serum-free medium increased hCG secretion by 125% (p = 0.05). Conversely, hLIF dose-dependently inhibited basal and cAMP-stimulated hCG secretion in trophoblasts derived during the second trimester and at term, as well as in cultured JEG-3 choriocarcinoma cells. LIF exhibited more potent inhibitory action in the second trimester, maximally reducing hCG production by 37% from that of control values (p < 0.05) at a dose of 10 nmol/l. These findings indicate that (1) LIF is produced by decidual cells throughout pregnancy and may play a different regulatory role of hCG production at different stages of gestation; and (2) gonadotropin synthesized in trophoblasts may, in part, regulate LIF production through a paracrine pathway.

Gynecomastia: pathomechanisms and treatment strategies.

Gynecomastia is common in adolescents and adults, and reflects an underlying imbalance in hormonal physiology in which there is an increase in estrogen action relative to androgen action at the breast tissue level. Most patients have persistent pubertal gynecomastia or breast glandular enlargement from medications, age-related reduction in testicular function, or idiopathic causes. Gynecomastia must be differentiated from pseudogynecomastia due to increased breast adipose tissue, as well as from breast carcinoma. The evaluation of the causes of gynecomastia can be accomplished through history, physical examination and a few laboratory tests. Painful gynecomastia of recent onset may respond to antiestrogen therapy. Surgical removal is the mainstay for long-standing gynecomastia or glandular enlargement that is unresponsive to medical therapy.

Comparison of production of choriogonadotropin inhibitory protein, prolactin and insulin-like growth factor binding protein-1 by human decidua in vitro.

We have previously demonstrated that human decidua produces a protein (decidual choriogonadotropin inhibitory protein, DCIP) that inhibits human chorionic gonadotropin (hCG) secretion from primary trophoblasts and JEG-3 choriocarcinoma cells. The present study was undertaken to examine the relationship of DCIP production to that of cell protein, prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1). Term decidual cells, isolated from placental membranes by enzyme digestion and density gradient centrifugation, were incubated for 12 days in serum-free CMRL-1066 medium which was changed daily. At the end of each experiment the DCIP in the decidual culture medium was measured by bioassay: the percentage reduction, from control, of hCG production by JEG-3 cells exposed to 30% DCIP-containing decidual culture medium. Prolactin, IGFBP-1 and hCG were measured by radioimmunoassay. The DCIP activity was maximal during the first 3 days in culture. The bioactivity of decidual culture medium collected after the 5th day of culture gradually decreased and medium obtained from the final day of culture actually stimulated hCG secretion in the bioassay. Decidual cell protein gradually declined from 100% on day 1 to 56% on the last day of culture. The concentrations of protein, PRL and IGFBP-1 in the decidual culture medium gradually decreased during the first 4-6 days, followed by a rise. In contrast, glucose increased with time in culture. Production of PRL, IGFBP-1 and decidual culture medium protein exhibited a significant quadratic effect over the 12 days in culture. There was a negative relationship between decidual cell protein and glucose (r = -0.95) and a positive correlation between cell protein and protein in the decidual culture medium (r = 0.58). The DCIP activity was related to cell protein (r = 0.39), protein concentration in decidual culture medium (r = 0.36), and inversely related to the glucose level (r = -0.41). There was no relationship between DCIP activity and PRL or IGFBP-1. These results indicate that maximal DCIP production occurs during the first several days in short-term culture of decidual cells and is related to decidual-cell viability. As decidual-cell viability decreases, there is less glucose consumption in the decidual culture medium and the higher glucose levels may be responsible for the stimulatory effect of medium collected at the end of the study on JEG-3 hCG secretion.