A double-antibody radioimmunoassay method was used for serial determinations of a tumor-antigen (TA-4) of cervical squamous cell carcinoma, and the correlation of serum antigen levels with the disease progess was investigated in 23 patients with cervical squamous cell carcinoma. Ten cases with widespread metastases received radiotherapy and/or chemotherapy. Nine of these cases who showed progression of the disease had a corresponding increase in serum antigen levels, while one case who had regression of the disease showed a corresponding decrease in serum antigen levels. Thirteen patients received radical surgery, and in all of these, high pretreatment antigen levels declined to undetectable levels 1 or 2 weeks after surgery. A panel of coded sera from the NCI-Mayo Clinic Serum Bank was also studied for evaluating the specificity of the assay. Thirteen of 25 patients (52%) with cervical squamous cell carcinoma showed positive serum antigen levels, while only one of 58 control cases (1.7%) showed false-positive result. These results suggest that serial TA-4 determinations may provide a useful method for evaluating regression or progression of the disease.
Effects of domperidone, a dopaminergic antagonist, on serum prolactin levels were studied in 6 normal men and 6 normal cyclic women at the different phases of their menstrual cycles (i.e., the follicular, the preovulatory and the luteal phases). Domperidone (10 mg, i.v.) caused significant increases in serum prolactin in all cases within 15 min after the injection. The prolactin response was significantly (p<0.01) higher in women than in men, and there was no significant difference in the prolactin responses among the three phases of the menstrual cycles. These results indicate that domperidone may be an effective stimulator of serum prolactin secretion in human beings.
The effect of the nongravid part of the uterus on corpus luteum (CL) activity was studied in rats bearing a single conceptus during midpregnancy. On day 7 (day 1 = insemination), the number of conceptuses was reduced to one by aspirating all but one conceptus (the aspiration group), by removing all of of the uterus except that containing a single conceptus (the hysterectomy group), or by aspirating conceptuses, as in the aspiration group, plus ligating the uterus, as in the hysterectomy group, but without removing the uterus (the sham hysterectomy group). Rats with a full complement of conceptuses (the intact control group) served as additional controls. Blood samples were obtained on days, 10, 12, and 15, to determine the effects of these procedures on the increase in serum progesterone that normally occurs between days 12 and 15 and to observe any related changes in serum LH between days 10 and 15. On day 15, the mean serum prgesterone concentrations and weights of the CL in the aspiration and sham hysterectomy groups were significantly lower than those in the intact control group. In the hysterectomy group, however, serum progesterone was even higher than in the intact control group, although the CL were significantly smaller than in the intact control group and were not different from those in the aspiration or sham hysterectomy groups. Serum LH on day 10 was significantly lower in the hysterectomy group than in any of the other groups; the latter were not significantly different from each other. By day 15, serum LH in the intact group had fallen to less than 50% of the value on day 10, while in the aspiration group, it remained as high as on day 10. In the hysterectomy group, there was no significant difference in serum LH concentrations between days 10 and 15. These results suggest that the nongravid part of the uterus inhibits progesterone secretion, and that in its absence, even a single conceptus can increase progesterone secretion after day 12 as much as can a full complement of conceptuses, but without also increasing the size of the CL. The uterus may exert this effect either through the pituitary or in cooperation with a pituitary factor, possibly LH.
On days 5, 10, 15 and 20 of pregnancy, rat corpora lutea (CL) were dissected and dissociated into single cell suspensions by enzyme treatments. The suspended luteal cells were allowed to sediment in a BSA gradient at 4 degrees C for 3.5 hours. Five fractions were collected from the top (Fraction (Fr.) 1) to the bottom (Fr. 5) of the gradient. Cells were incubated in serum-free DME-F12 for 20 hours with or without hCG (100 ng/ml) to test them functionally, and the accumulation of progesterone and testosterone was determined by radioimmunoassay. To assess 3,3-hydroxysteroid dehydrogenase (HSD) activity, a histochemical suspension-staining procedure was used. Cells were examined by light microscopy, and the percentage of cells containing dark blue formazan deposits and their diameters were determined in at least 40 microscopic fields. The number of cells staining for 3 beta-HSD did not vary by day 15 but decreased from 141.6 +/- 16.5 X 10(3) cells/CL on day 15 to 113.8 +/- 13.2 X 10(3) cells/CL on day 20 of pregnancy. However, 3 beta-HSD-positive cells maintained the same levels of progesterone secretion until the advent of luteolysis, then they increased in size progressively throughout pregnancy. In BSA gradients, the relatively larger 3 beta-HSD-positive cells migrated faster than the smaller 3 beta-HSD-positive cells on each day of pregnancy. The diameters of 3 beta-HSD-positive cells differed significantly in Frs. 2, 3, 4 and 5 on days 15 and 20 of pregnancy. On day 15 of pregnancy, less progesterone accumulated in wells containing 3 beta-HSD-positive cells from Fr. 2 (mean diameter; 24.96 microns) than from Fr. 3, Fr. 4 and Fr. 5 (mean diameters; 27.20, 30.79 and 31.28 microns, respectively) but the Fr. 2 cells responded more to hCG stimulation. Fr. 2 also showed a higher ratio of testosterone accumulation to progesterone accumulation than the other fractions. The response to hCG stimulation of cells in Fr. 2 tended to be higher than that in Fr. 3 on day 20 of pregnancy. These data suggest that the steroidogenic rat luteal cells are comprised of morphologically and functionally different cell types after day 15 of pregnancy. No stimulating nor inhibiting effects were observed in co-incubation of cells from Fr. 2 with cells from Fr. 3 or Fr. 4 on days 15 and 20 of pregnancy.
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