Time-courses of the appearance/disappearance of nuclear androgen + receptor complexes in the brain and adenohypophysis following testosterone administration/withdrawal to castrated male rats: relationships with gonadotropin secretion

We characterized the temporal dynamics of brain and pituitary cell nuclear androgen receptor binding and serum androgen and gonadotropin levels associated with the implantation and removal of testosterone (T)-filled Silastic capsules into performed s.c. flank pouches of castrated, awake male rats. These capsules produced serum T levels in the physiologic range. The number of cell nuclear androgen + receptor complexes, as measured in an exchange assay using [3H]R1881, increased 15-fold at 0.5 h after capsule insertion in the HPAS (combined hypothalamus, preoptic area, amygdala and septum) and anterior pituitary gland, but then showed a second progressive rise within the next 8 h. This pattern suggests that T exerts an initial action in the tissues to alter the affinity and/or number of available androgen receptors. There was a lag time of 2-4 h to the first indication of negative feedback suppression of LH secretion. Serum LH levels declined only slightly at 4 h after capsule insertion but continued to fall thereafter, reaching undetectable values by 24 h. In contrast, serum FSH levels declined only slightly after 24 h of T exposure. After removal of the T capsules, serum T levels declined to castrate values within 2 h at which time the level of androgen + receptor complexes had fallen to 60% in the brain and pituitary. Serum LH and FSH concentrations were unchanged at 2 h after capsule removal, but rose significantly within the next 2 h. The data indicate that the occupation of androgen receptors rapidly changes in response to variations in circulating T in a fashion that implicates their involvement in the expression of this steroid's negative feedback actions on gonadotropin secretion.     

Studies on the Methyl Green-DNA complex and its dissociation by drugs.

Spectrophotometric results indicated that Methyl Green bound stably to native calf thymus DNA and to poly[d(A-T)] but to a lesser extent to phiX 174 DNA, tRNAs, and poly(dG-dC), a copolymer that exists preferentially in the A conformation. Exposing the Methyl Green-DNA complex to graded concentrations of ethyl alcohol liberated part of the dye slowly by a zero-order reaction; higher alcohol concentrations which cause the B leads to A transition of DNA released the bulk of Methyl Green. The viscosity of the Methyl Green-DNA complex was significantly lower than that of the uncomplexed DNA. The dye was progressively liberated from DNA by 1.5 x 10(-1) M NaCl and by much lower concentrations of Mg2+; in its stoichiometric complex with DNA, it increased Tm by approximately 12 degrees C. A series of DNA-complexing drugs displaced Methyl Green from DNA at exponential rates and to end points which were correlated. End points of displacement correlated with the abilities of drugs to unwind supercoiled DNA, to labilize ribosomes to heat, and to eliminate a kanamycin resistance determinant from an R factor carried by Salmonella typhimurium. Additional correlations between Methyl Green displacement and biochemical-biological activities of displacing drugs are cited. In conjunction with these findings, our results suggest that Methyl Green displacement analysis is a useful biochemical screen for the detection or development of biologically active compounds which bind to DNA.     

Significant non-existence of sequences in genomes and proteomes

Minimal absent words (MAWs) are minimal-length oligomers absent from a genome or proteome. Although some artificially synthesized MAWs have deleterious effects, there is still a lack of a strategy for the classification of non-occurring sequences as potentially malicious or benign. In this work, by using Markovian models with multiple-testing correction, we reveal significant absent oligomers, which are statistically expected to exist. This suggests that their absence is due to negative selection. We survey genomes and proteomes covering the diversity of life and find thousands of significant absent sequences. Common significant MAWs are often mono- or dinucleotide tracts, or palindromic. Significant viral MAWs are often restriction sites and may indicate unknown restriction motifs. Surprisingly, significant mammal genome MAWs are often present, but rare, in other mammals, suggesting that they are suppressed but not completely forbidden. Significant human MAWs are frequently present in prokaryotes, suggesting immune function, but rarely present in human viruses, indicating viral mimicry of the host. More than one-fourth of human proteins are one substitution away from containing a significant MAW, with the majority of replacements being predicted harmful. We provide a web-based, interactive database of significant MAWs across genomes and proteomes.     

Protein and energy self-selection of turkey hens. Serum prolactin and luteinizing hormone concentrations.

1. The incidence of broodiness was four times as high among turkey hens fed a complete control diet than among hens allowed to self-select their diet from two different feed sources, one being relatively high in protein and the other relatively high in energy (i.e. split-diet). 2. Among non-broody birds, hens fed the split-diet had a significantly lower serum prolactin concentration in the third month of production as compared to control hens. 3. Hens in their second season of egg production had significantly lower serum luteinizing hormone concentrations during the latter stages of egg production than did first season hens.