GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 85,000,000 nucleotides in 67,000 entries from a total of 3,000 organisms. The input stream of data coming into the database is primarily as direct submissions from the scientific community on electronic media, with little or no data being keyboarded from the printed page by the databank staff. The data are maintained in a relational database management system and are made available in flatfile form through on-line access, and through various network and off-line computer-readable media. The data are also distributed in relational form through satellite copies at a number of institutions in the U.S. and elsewhere. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

Electronic data publishing and GenBank.

GenBank, the national repository for nucleotide sequence data, has implemented a new model of scientific data management, which we term electronic data publishing. In traditional publishing, both scientific conclusions and supporting data are communicated via the printed page, and in electronic journal publishing, both types of information are communicated via electronic media. In electronic data publishing, by contrast, conclusions are published in a journal while data are published via a network-accessible, electronic database.

GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 56,000,000 nucleotides in 45,000 entries. The input stream of data coming into the database has largely been shifted to direct submissions from the scientific community on electronic media. The data have been installed in a relational database management system and are made available in this form through on-line access, and through various network and off-line computer-readable media. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis.

The concentrations of a small number of mRNAs in the rat ventral prostate increase after castration and then decrease upon androgen treatment. Since the repression of specific gene expression may be important in the regulation of organ growth, we have cloned a cDNA for an androgen-repressed mRNA, the concentration of which increased 17-fold 4 days after castration, and this increase was reversed rapidly by androgen treatment. By sequence analysis the androgen-repressed mRNA was identified as that coding for sulphated glycoprotein 2.

The effect of oestriol and tamoxifen on oestradiol induced prolactin secretion in anaesthetised rats.

In ovariectomized rats oestradiol and oestriol administered sc for 5 days increased basal plasma prolactin in a dose related manner to similar maximal values. The data fitted log dose-response curves. Oestradiol was about 12 times more potent than oestriol. These dose response relationships were retained on thyrotrophin releasing hormone (TRH) administration (50 ng iv, blood sampled 5 min post TRH). In addition, significantly higher maximal response values for both oestradiol and oestriol were now seen. The relative potency also increased in oestradiols favour. We subsequently examined the effect of co-administering oestriol with oestradiol on plasma secretory responses to a single dose of oestradiol in young male rats: Oestriol (30 micrograms) potentiated increases in basal plasma prolactin, TRH stimulated prolactin secretion and radioimmunoassayable pituitary prolactin in rats in response to a single sc injection of oestradiol (10 micrograms). Tamoxifen, administered once also potentiated these responses to a single sc injection of oestradiol. However, if the tamoxifen was administered sequentially i.e. 48 and 24 h before or 48 and 24 h before and simultaneous with the oestradiol the potentiation was completely reversed.

Sequence and expression of human estrogen receptor complementary DNA.

The mechanism by which the estrogen receptor and other steroid hormone receptors regulate gene expression in eukaryotic cells is not well understood. In this study, a complementary DNA clone containing the entire translated portion of the messenger RNA for the estrogen receptor from MCF-7 human breast cancer cells was sequenced and then expressed in Chinese hamster ovary (CHO-K1) cells to give a functional protein. An open reading frame of 1785 nucleotides in the complementary DNA corresponded to a polypeptide of 595 amino acids and a molecular weight of 66,200, which is in good agreement with published molecular weight values of 65,000 to 70,000 for the estrogen receptor. Homogenates of transformed Chinese hamster ovary cells containing a protein that bound [3H]estradiol and sedimented as a 4S complex in salt-containing sucrose gradients and as an 8 to 9S complex in the absence of salt. Interaction of this receptor-[3H]estradiol complex with a monoclonal antibody that is specific for primate ER confirms the identity of the expressed complementary DNA as human estrogen receptor. Amino acid sequence comparisons revealed significant regional homology among the human estrogen receptor, the human glucocorticoid receptor, and the putative v-erbA oncogene product. This suggests that steroid receptor genes and the avian erythroblastosis viral oncogene are derived from a common primordial gene. The homologous region, which is rich in cysteine, lysine, and arginine, may represent the DNA-binding domain of these proteins.