Single follicles and fragments of perifollicular stroma from normal human ovaries were separately incubated in vitro with labeled C19 neutral steroids, the tissues used in any one experiment being derived from the same ovary. The comparative utilization by these tissues of dehydroepiandrosterone-4-14C for the formation of androgens and estrogens and the interconversions of androstenedione-4-14C and testosterone-1,2-3H and their aromatization by the 2 types of tissues was studied in these experiments. Dehydroepiandrosterone-4-14C was transformed to androstenedione by both types of tissues and to a much lesser extent to testosterone. The extent of these transformations was different in tissues obtained from different ovaries. The transformation of testosterone→androstenedione was observed to be quantitatively greater than the reverse reaction in both the ovarian compartments studied. The aromatization capacity of the follicles was rather limited (about 0.2% of the substrate) and the stromal tissue was inactive in this respect.
ABSTRACT We have previously reported that the LH-induced decrease in the concentration of ovarian cyclic GMP (cGMP) in the rabbit was accompanied by a drop in ovarian guanylate cyclase activity. The present experiments were carried out to see if the increase in cGMP concentration that occurs in immature rat ovaries after stimulation with pregnant mare serum gonadotrophin (PMSG) is also accompanied by changes in guanylate cyclase activity. Total ovarian cGMP, along with ovarian weight, was found to be increased at 16 h after PMSG treatment. Ovarian concentrations of cGMP, however, increased only after that period (at 20, 24 and 48 h) and the increase was progressive. Guanylate cyclase activity was found in both the cytosol and 100 000 g particulate fractions of the immature rat ovaries. Forty-three hours after PMSG treatment, activity in the particulate fraction was found to be significantly increased. This increase in guanylate cyclase activity was also found at 20 h but not at 16 h. Thus, the increase in ovarian cGMP concentration in immature rats after PMSG treatment was accompanied by increased guanylate cyclase activity. J. Endocr. (1985) 107, 77–81
An optimal amount of labile zinc (Zn 2+ ) is essential for proliferation of human cells, where Zn 2+ levels that are too high or too low cause cell cycle exit. Tumors of the breast have been characterized by high levels of total Zn 2+ . Given the role of Zn 2+ in proliferation of human cells and elevation of zinc in breast cancer tumors, we examined the concentration of total and labile Zn 2+ across a panel of 5 breast cancer cell lines, compared to the normal MCF10A cell line. We found that three cell lines (MDA-MB-231, MDA-MB-157, and SK-Br-3) showed elevated labile Zn 2+ in the cytosol, while T-47D showed significantly lower Zn 2+ , and MCF7 showed no change compared to MCF10A cells. There was no change in total Zn 2+ across the cell lines, as measured by ICP-MS, but we did observe a difference in the cells ability to accumulate Zn 2+ when Zn 2+ in the media was elevated. Therefore, we examined how proliferation of each cell line was affected by increases and decreases in the media. We found striking differences, where three cancer cell lines (MDA-MB-231, MDA-MB-157, and MCF7) showed robust proliferation in high Zn 2+ at concentrations that killed MCF10A, T-47D, and SK-Br-3 cells. We also discovered that 4 of the 5 cancer cell lines demonstrate compromised proliferation and increased cell death in low Zn 2+ , suggesting these cells may be addicted to Zn 2+ . Overall, our study suggests significant differences in Zn 2+ homeostasis and regulation in different types of breast cancer cells, with consequences for both proliferation and cell viability.
The intravenous infusion of 18-hydroxycorticosterone in a normal adult unanesthetized duck produced an important and significant increase in the volume and on the total output of sodium by the salt gland.
ABSTRACT The in vitro biosynthesis of androgenic steroids by surviving human normal and »Stein-Leventhal type« ovarian slices was studied. The tissue slices were incubated in a Krebs-Ringer-phosphate-glucose medium ( p H : 7.4) with pregnenolone, progesterone, 17α-hydroxyprogesterone and androstenedione added as substrates. The incubations were supplied with HCG as cofactor (1000 IU/vessel) and the reactions left to proceed for 6 or 24 hours. After incubation, the medium was extracted with chloroform and transformation products isolated by paper chromatography. Individual substances were characterized by chromatographic mobility studies, preparation of derivatives and spectrophotometric techniques. The following results were obtained: qualitatively no differences could be noted between the metabolic activity of ovarian slices of either origin. Quantitatively, »Stein-Leventhal type« slices showed an accelerated rate of production in all intermediary reactions, especially in the production of androstenedione and testosterone. In addition to the direct intermediaries, four C20 reduced transformation products of progesterone and 17α-hydroxyprogesterone were isolated from experiments involving both normal and micropolycystic ovarian slices.
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