We have identified two regions of non-random purine/pyrimidine strand asymmetry that were nearly identical in sequence in the 5' flanking (promoter) regions of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene and the human MUC1 gene. These regions contain perfect mirror repeat elements, a sequence motif previously found to be associated with the formation of H-DNA conformations. In this report we demonstrate that a single-stranded non-B DNA conformation exists at low pH in supercoiled plasmids containing the similar mirror repeat elements, and that S1 nuclease digestion maps the single-stranded region to the position of the mirror repeats. In addition, we identify a nuclear protein of approximately 27 kD that binds to single-stranded oligonucleotides corresponding to the purine-rich strand of this region, but not to the pyrimidine-rich strands or to double-stranded oligonucleotides with corresponding purine/pyrimidine strand asymmetry.

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The concentration of oestradiol-17beta was measured by radioimmunoassay in the milk and blood of lactating buffaloes after insemination. The concentration of oestradiol-17beta in milk was observed to be two to three times higher when compared with that in plasma samples. Major peaks of oestradiol-17beta in milk coincided with similar but smaller peaks occurring in plasma samples. In animals which were not pregnant, the major peak of oestradiol-17beta was recorded on the day of oestrus.

Similar imperfect purine/pyrimidine mirror repeat (PMR) elements have previously been identified upstream of the human MUC1 mucin and CFTR genes. These elements confer S1 nuclease sensitivity on isolated plasmid DNA at low pH. We now present a detailed characterization of the non-B DNA structure responsible for S1 nuclease sensitivity upstream of the MUC1 gene. A ϳ90-base pair (bp) DNA fragment containing a 32-bp PMR element termed M-PMR3 was subcloned into a recombinant vector. This fragment conferred S1 nuclease sensitivity on the resulting supercoiled plasmid. High resolution mapping of sites reactive to S1 and P1 nucleases demonstrates that cleavage occurs within the M-PMR3 element. High resolution mapping with chemical agents selective for non-B DNA provides evidence that M-PMR3 adopts an H-DNA structure (intramolecular triple helix) in the less common H-y5 isomer at low pH. This result is observed in the presence or absence of Mg 2؉. Mutation of the native M-PMR3 element to create perfect homopurine/homopyrimidine mirror symmetry alters the preferred folding to the more common H-y3 triplex DNA isomer. These results demonstrate that imperfections in mirror symmetry can alter the relative stabilities of different H-DNA isomers.

Acta Obstet Gynecol Scand 1992; 71 Suppl 155: 31-38 During the last two decades, considerable experimental evidence has been collected indicating that epithelial ovarian cancer might be gonadotropin dependent. LH and FSH receptors have been described in some of these tumors. The proliferation of ovarian cancer cells could be stimulated in vitro by gonadotropins. Suppression of endogenous LH and FSH secretion by GnRH-agonist treatment inhibited the growth of experimental or heterotransplanted ovarian cancers in various animal models. A number of recent phase II clinical trials have shown that the application of GnRH-agonists can lead to remission or stable disease in patients with relapsed advanced ovarian cancer. At present, prospective controlled clinical studies are being performed to assess the efficacy of GnRH-agonist treatment in addition to conventional surgical and cytostatic therapy in ovarian cancer in FIGO stages III and IV. Also, direct effects of GnRH analogues on ovarian cancer seem possible: a GnRH-like protein has been found in the human ovary. Our group discovered and partially characterized a specific GnRH-binding site (mol. wt 63.2 kDa) in ovarian cancer which is very similar to other human extrapituitary GnRHbinding sites of the low affinity, high capacity type, e.g. in breast cancer or the placenta. Recently, other groups have described also high affinity GnRH-agonist binding sites in ovarian cancer as well as in other extra pituitary tissues. First results from our laboratory indicate that the proliferation of certain ovarian cancer cell lines in vitro is reduced by both agonistic and antagonistic analogues of GnRH. Other authors were able to inhibit gonadotropin-induced in vitro proliferation of ovarian cancer cell lines by co-incubation with a GnRH-agonist. Thus GnRH -or a related compound -might act as an autocrine regulator of ovarian cancer proliferation, a finding which might be useful for the development of new therapeutic approaches.For more than a century it has been known that married women are much less likely to develop ovarian cancer (DC) than are unwed females (1). Some authors believed that this phenomenon was due to the suppression 'of the libido in unmarried women, causing hyperemia of the genital organs. Most gynecologists at that time, however, supposed that the higher incidence of DC in female celibates was caused by menstrual hyperemia, which occurred naturally more often in this population than in married women who had fewer menstruations due to pregnancies, child-bed and lactation (for review, see 2).Since the 1970s it has been shown by several investigators that the number of pregnancies and the duration of oral contraceptive use are significantly inversely related to the incidence of OC (e.g. 3-6). Fathalla (3) was the first to suggest that the incessant monthly ovulation which is characteristic of our species, in the 20th century at least, is a causal factor for the development of DC, due to the repeated rupture Acta Obstet Gynecol Scand Suppl J55