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B F Hales

Publications and source records attributed to B F Hales.

70 records · Page 4Linked to original sources
PubMed1982

Regulation of epididymal glutathione S-transferases: effects of orchidectomy and androgen replacement.

Glutathione S-transferases, a family of enzymes that catalyze the conjugation of glutathione to a variety of substrates, are present in rat epididymis. In order to study the hormonal regulation of these enzymes in this tissue, adult rats were orchidectomized and implanted with empty or androgen-filled polydimethylsiloxane capsules. Orchidectomy alone significantly decreased caput-corpus epididymal glutathione S-transferase activity toward 2 substrates, 1-chloro-2,4-dinitrobenzene and trans-4-phenylbut-3-en-2-one, but had no effect on transferase activity toward the third substrate, 1,2-dichloro-4-nitrobenzene. In contrast to these results, orchidectomy did not alter glutathione S-transferase activity towards these substrates in the cauda epididymidis. Androgen replacement with testosterone prevented the orchidectomy-induced decrease in caput-corpus glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene and trans-4-phenylbut-3-en-2-one and had no effect on transferase activity toward 1,2-dichloro-4-nitrobenzene. The effects of 5 alpha-reduced metabolites of testosterone were also studied. Both dihydrotestosterone and 5 alpha-androstan-3 alpha, 17 beta-diol maintained caput-corpus glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene, although a lower dose of dihydrotestosterone was sufficient; these 1 androgens were unable to maintain activity toward trans-4-phenylbut-3-en-2-one and caused a suprastimulation of activity toward 1,2-dichloro-4-nitrobenzene above control values. The third 5 alpha-reduced androgen studied, 5 alpha-androstan-3 beta, 17 beta-diol had no effect on the transferase activity toward any of the 3 substrates. These results demonstrate that the epididymal glutathione S-transferases are under separate control and are differentially regulated by testosterone and its 5 alpha-reduced metabolites.

Androgens↗
PubMed1980

The presence and longitudinal distribution of the glutathione S-transferases in rat epididymis and vas deferens.

The presence of the glutathione S-transferases, enzymes that catalyse the conjugation of glutathione with a variety of compounds, is reported here, for the first time, in the mammalian epididymis-vas deferens. These glutathione S-transferases, approx. 50% of those from rat liver on a per-mg-of-protein basis, are resolved by isoelectric focusing into six peaks, each with a characteristic isoelectric point and substrate specificity. By these same criteria, the first three peaks (pI 8.9, 8.2 and 7.8) can be identified as transferases B, A and C respectively. The fifth peak (pI7.2) may correspond to transferase M; the fourth (pI7.5) and sixth (pI7.0) peaks do not correspond to previously described transferases. The distribution of transferase activity towards any one substrate studied differs in sequential sections of the epididymis and vas deferens; in addition, the longitudinal-distribution pattern differs for each of the three substrates studied. Isoelectric focusing of the cytosol fractions of the different sections further substantiates these observations. The potential significance of these enzymes and of their distribution in terms of epididymal function, maturation of spermatozoa, is discussed.

Animals↗
PubMed1978

Isoelectric focusing of glutathione S-transferases from rat liver and kidney.

The glutathione S-transferases that were purified to homogeneity from liver cytosol have overlapping but distinct substrate specificities and different isoelectric points. This report explores the possibility of using preparative electrofocusing to compare the composition of the transferases in liver and kidney cytosol. Hepatic cytosol from adult male Sprague-Dawley rats was resolved by isoelectric focusing on Sephadex columns into five peaks of transferase activity, each with characteristic substrate specificity. The first four peaks of transferase activity (in order of decreasing basicity) are identified as transferases AA, B, A and C respectively, on the basis of substrate specificity, but the fifth peak (pI6.6) does not correspond to a previously described transferase. Isoelectric focusing of renal cytosol resolves only three major peaks of transferase activity, each with narrow substrate specificity. In the kidney, peak 1 (pI9.0) has most of the activity toward 1-chloro-2,4-dinitrobenzene, peak 2 (pI8.5) toward p-nitrobenzyl chloride, and peak 3 (pI7.0) toward trans-4-phenylbut-3-en-2-one. Renal transferase peak 1 (pI9.0) appears to correspond to transferase B on the basis of pI, substrate specificity and antigenicity. Kidney transferase peaks 2 (pI8.5) and 3 (pI7.0) do not correspond to previously described glutathione S-transferases, although kidney transferase peak 3 is similar to the transferase peak 5 from focused hepatic cytosol. Transferases A and C were not found in kidney cytosol, and transferase AA was detected in only one out of six replicates. Thus it is important to recognize the contribution of individual transferases to total transferase activity in that each transferase may be regulated independently.

Animals↗
PubMed1976

A sex difference in hepatic glutathione S-transferase B and the effect of hypophysectomy.

The glutathione S-transferases are a group of proteins with overlapping substrate specificities and ligand-binding capacities. This report examines certain approaches to the measurement of transferase B (ligandin) in the rat liver. The ratio of catalytic activities toward 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene gives some indication of the relative proportions of the various transferases present in 100 000 g supernatants. The fraction of catalytic activity towards 1-chloro-2,4-dinitrobenzene, due to transferase B, was best measured by immunoprecipitation with anti-(transferase B). Male rat liver exhibited three times more activity towards 1,2-dichloro-4-nitrobenzene than female tissue; however, the activities towards 1-chloro-2,4-dinitrobenzene were almost identical. By assuming a specific activity of 11 mumol/min per mg, immunoprecipitable transferase B comprised 4.5 +/- 0.2% of total protein in the 100 000 g supernatant of female rat liver, and 70% of the transferase activity towards 1-chloro-2,4-dinitrobenzene. The amount of transferase B in the 100 000 g supernatant from male rat liver is significantly lower with respect to both fraction of total protein (3.3 +/- 0.2%) and overall transferase activity towards 1-chloro-2,4-dinitrobenzene (48%). Hypophysectomy eliminated this sex difference in the hepatic concentration of glutathione S-transferase B.

Animals↗
PubMed1976

Developmental aspects of glutathione S-transferase B (ligandin) in rat liver.

The postnatal development in male Sprague-Dawley rats of hepatic glutathione S-transferase B (ligandin) in relation to the other glutathione S-transferases is described. The concentration of glutathione S-transferase B in 1-day-old male rats is about one-fifth of that in adult animals. The enzyme reaches adult concentrations 4-5 weeks later. When assessed by substrate specificity or immunologically, the proportion of transferase B relative to the other glutathione S-transferases is high during the first week after birth. At this age, 67.5% of the transferase activity towards 1-chloro-2,4-dinitrobenzene is immunoprecipitable by anti-(transferase B), compared with about 50% in adults and older pups. Between the second and the fifth postnatal week, the fraction of transferase B increases in parallel fashion with the other transferases in hepatic cytosol. Neither L-thyroxine nor cortisol induce a precocious increase in glutathione S-transferase activity. Phenobarbital did induce transferase activity towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene in both pups and adults. The extent of induction by phenobarbital was a function of basal activity during development such that the percentage stimulation remained constant from 5 days postnatally to adulthood.

Animals↗
PubMedDate not supplied

Paternal cyclophosphamide treatment of rats causes fetal loss and malformations without affecting male fertility.

The use of cytotoxic, mutagenic and carcinogenic agents as treatment for various types of cancer may be particularly hazardous in men of reproductive age as there exists the possibility that this may lead to congenital malformations in the progeny. Such agents can affect fertility and other aspects of male reproductive function, for example, treatment with anti-cancer drugs such as cyclophosphamide has been associated with oligozoospermia, azoospermia and increased levels of serum follicle-stimulating hormone (FSH). Depending on the cumulative dose and the duration of treatment, spermatogenesis often returns but this may take years. The relevance of the effects of such chemicals on the male reproductive system to the offspring is poorly understood. We have set out to determine whether present tests of male reproductive function (that is, endocrine status, numbers of spermatozoa, fertility) can predict deleterious effects of a paternally administered agent on the offspring. Here, we report that chronic administration in rats of low doses of the widely used drug cyclophosphamide had minimal effects on the male reproductive system and fertility, but resulted in malformations and retardation of growth in the surviving fetuses and a high frequency of fetal death. Thus, adverse effects on the fetus cannot be predicted from the effects of a drug on the male reproductive system.

Abnormalities, Drug-Induced↗