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C Chubb

Publications and source records attributed to C Chubb.

49 records · Page 3Linked to original sources
PubMed1984

Cytoplasmic malic enzyme and testicular steroidogenesis in mice.

The malate shuttle has been hypothesized as a source of the intramitochondrial NADPH required for cholesterol side-chain cleavage. In the present report, the role of the malate shuttle in testicular steroidogenesis was investigated by employing mouse mutants deficient in cytoplasmic malic enzyme, a required component of the shuttle. Androgen-dependent parameters plus testosterone secretion by in vitro perfused testes were similar for the mutants and their normal siblings. The data suggest that an active malate shuttle is not required for cholesterol side-chain cleavage in mouse testes.

Animals↗
PubMed1983

In vitro perfusion of isolated mouse testes: a model system for investigating testicular steroidogenesis.

1. A procedure was developed to perfuse isolated mouse testes in vitro and investigate testosterone secretion. 2. The perfused testis preparation was validated by determining organ edema, glucose uptake, enzymatic and morphological indices of cellular integrity, and testosterone secretion in the absence and presence of LH and other pituitary peptides. 3. The results establish that this procedure can be exploited as a model system to investigate biochemical, physiological, and genetic aspects of steroidogenesis and Leydig cell function in the mouse, and presumably other small rodents as well.

Animals↗
PubMed1983

Steroid secretion by mouse testes perfused in vitro.

We determined the concentration of steroids in blood plasma of CBF1 male mice and the steroidogenic potential of the mouse testis. Steroid secretion rates are based on measuring selected C18, C19, and C21 steroids in the venous effluent of testes perfused with a defined medium containing luteinizing hormone. Steroids were isolated by thin-layer and/or column chromatography and quantified by radioimmunoassay. These include pregnenolone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, 3 alpha-androstanediol, and 3 beta-androstanediol. Testosterone is the primary steroid secreted by mouse testes perfused in vitro and is the chief androgen present in blood plasma. Pregnenolone, an obligatory intermediate in steroid synthesis, is converted to testosterone via two separate steroidogenic pathways in approximately equal proportions. This is unlike other species in which testosterone biosynthesis proceeds preferentially via either the delta 4 or the delta 5 pathway. Our results, taken together, provide the first comprehensive assessment of Leydig cell steroidogenic activity in the mouse, demonstrate putative enzymatic pathways subserving androgen biosynthesis, and establish the predominant steroids in the peripheral circulation of adult mice.

Androgens↗
PubMed1982

Vasculature of the mouse, rat, and rabbit testis-epididymis.

The arrangement of blood vessels serving the testis-epididymis vas investigated microscopically in the mouse, rat, and rabbit. Blood vessels were visualized by infusing liquid silicone rubber into the vessels and subsequently clearing the surrounding tissue. Comprehensive illustrations of the vasculature were prepared from three-dimensional examinations. Arterial and venous vessels serving the testis-epididymis follow similar routes in all three species. However, the arrangements and characteristics of the blood vessels demonstrate dramatic species differences. For example, arteries within the testes have tight coils in the mouse and artery-artery anastomoses in the rat. Veins form vascular pathways that connect the testis and efferent ductules in all three species but also form a connection between the testis and cauda epididymidis in the rabbit only. Testosterone concentrations were determined in blood obtained by micropuncture of selected testis-epididymal veins. The measurements establish that the highest levels of testosterone are found in testicular surface veins. Also, vas deferential veins of the rabbit had significant amounts of testosterone. Studies of the blood-vessel volumes suggested that the volumes of arteries and veins in the testis are similar, whereas venous volumes exceed arterial volumes in all of the other organs examined. The studies provide comprehensive information about the architecture and physiology of blood vessels serving the testis-epididymis in the mouse, rat, and rabbit. Each species exhibits diversity in the vasculature and testosterone content of the veins. Veins connecting the testis to the efferent ductules and cauda epididymidis may provide for the preferential delivery of testicular secretions to androgen-dependent organs before the secretions are metabolized or diluted in the systemic blood.

Animals↗
PubMed1981

Assessment of testicular testosterone production and Leydig cell structure.

Advances in two techniques have made the problem of assessing the acute and/or chronic effects of toxic agents on Leydig cell structure and testosterone synthesis and secretion amenable to study. First, in vitro testicular perfusion has been perfected to a point where it closely resembles in situ testosterone secretion. Second, now it is possible to quantify the proportion of Leydig cell cytoplasm occupied by the cellular organelles which contain steroidogenic enzymes. Herein, we report that inhibition of Leydig cell steroidogenic enzymes is reflected by reduced testosterone secretion by in vitro perfused rat and rabbit testes. Moreover, the activity of specific steroidogenic reactions can be monitored by measuring the secretion of reaction substrate(s) and product(s) from in vitro perfused testes. Testosterone secretion by in vitro perfused testes from five species is highly and positively correlated with the volume density of smooth endoplasmic reticulum in Leydig cell cytoplasm. Exploitation of these findings will allow toxicologists to quantitatively assess the effect of toxicants on Leydig cell testosterone biosynthesis and secretion, to identify the specific steroidogenic enzymes affected, to assess whether the membranous environment of the steroidogenic enzymes is compromised, and perhaps even to predict the deleterious effect of a toxic agent on Leydig cell steroidogenic function from a stereological assessment of Leydig cell ultrastructure.

Aging↗
PubMed1980

Mathematical model of steroidogenesis in rat and rabbit testes.

The purpose of this study was to develop a mathematical model of testicular steroidogenesis which could not only predict steroid secretion but also could be implemented to test the validity of assumptions used in studies of testicular testosterone biosynthesis in rats and rabbits. Since the two predominant fates of testicular steroids are metabolism and secretion, we hypothesized that the data for construction of the model could be observed testicular steroid secretions and that these data could then be used to elucidate intratesticular steroid conversions. Equations based on steroid secretion by testes perfused in vitro were developed to estimate transition probabilities corresponding to steroid secretion or conversion. The model was tested by comparing the predicted steroid secretion rates with those observed for control testes perfused in vitro. In addition, the transition probabilities determined by the model were used to indicate the predominant series of reactions for converting pregnenolone to testosterone. The results presented herein confirm the capability of the model to predict steroid secretion rates and to predict preferred pathways for testosterone biosynthesis in maximally stimulated testes perfused in vitro. Moreover, the model construction required only algebra and steady-state measurements.

Animals↗
PubMed1979

Steroid secretion by in vitro perfused testes: testosterone biosynthetic pathways.

Alternative metabolic pathways for the biosynthesis of testosterone from pregnenolone exist in mammalian testes. The following experiments were designed to identify the preferred testosterone biosynthetic pathway in rat and rabbit testes. The experimental protocol included the infusion of steroidogenic reaction inhibitors and testosterone biosynthetic intermediates into testes perfused in vitro. Under these conditions, the testicular steroid secretions were a measure of specific reaction activities. Infusion of medrogestone (6,17-dimethyl-4,6-pregnadiene-3,20-dione, Ayerst), an inhibitor of delta5-4isomerization, permitted the reactions converting pregnenolone to androstenediol to be studied separately from those converting progesterone to testosterone. For example, the activity of the pregnenolone vector 17alpha-hydroxypregnenolone reaction was measured as the total of the 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol secreted by medrogestone-inhibited testes. The reactions convering delta5-3beta-hydroxysteroids to delta4-3-ketosteroids were studied in testes infused with SU-10603 (7-chloro-3,4-dihydro-2-[3-pyridyl]-1(2H)-naphthalenone. Ciba-Geigy), an inhibitor of 17alpha-hydroxylation and C-17, C-20 cleavage reactions. The results indicated that preferred testosterone biosynthetic pathways are present and different in rat and rabbit testes.

Animals↗
PubMedDate not supplied

Genetically defined mouse models of male infertility.

The review has four objectives. The first objective is to summarize our studies of gene mutations that induce infertility in male mice. The second objective is to stress the power of mouse genetics and its application to male reproductive biology. The third objective is to provide useful references to the literature about gene mutations affecting male mouse fertility. Our goal is to cite references that can be used as a starting point for reading, not to present a comprehensive list of references. The fourth objective is to present a summary of selected data collected from mice representing 21 mouse strains.

Animals↗
PubMedDate not supplied

Oligotriche and quaking gene mutations. Phenotypic effects on mouse spermatogenesis and testicular steroidogenesis.

The phenotypic actions of the oligotriche gene mutation on testicular function have not been elucidated, although it is known that male mice homozygous for the mutation are infertile. In the present study, the effect of the oligotriche gene mutation on mouse testicular function was analyzed by comparing normal and mutant mice. Spermatogenesis was analyzed by enumerating germ cells in seminiferous tubules at specific stages of spermatogenesis and by electron microscopy. Steroidogenic potential was estimated by radioimmunometric determination of testosterone secreted by testes perfused in vitro. Parallel studies were completed for male mice homozygous for the quaking gene mutation, a mutation known to cause male mouse sterility by disrupting sperm tail development. The experimental results suggest that the oligotriche and quaking gene mutations interfere with sperm tail formation by different mechanisms. Testicular steroidogenesis was not affected by either gene mutation. The results provide the first evidence that the oligotriche gene mutation induces male mouse sterility by effecting the complete absence of a sperm tail. This phenotypic action is different from that of the quaking gene mutation.

Animals↗