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Biomedical subjects

J M Davidson

Publications and source records attributed to J M Davidson.

At least 163 records · Page 9Linked to original sources
PubMed1982

Effects of a potent dopamine receptor agonist, RDS-127, on penile reflexes and seminal emission in intact and spinally transected rats.

Administration of RDS-127 (3.0 mg/kg) induced seminal emission within three minutes of IP injection and suppressed the display of penile reflexes in intact and spinally transected rats. In Experiment 1, RDS-127 was administered to intact, sexually experienced rats in a protocol previously demonstrated to selectively lower the ejaculatory threshold of copulating animals. The incidence of seminal emission was significantly elevated by RDS-127 but penile reflexes were present in only 8% of the drug-treated rats, compared to 59% of controls. In Experiment 2, seminal emission was induced 2.3 +/- 0.4 (S.E.) minutes from injection of RDS-127. Animals which responded to RDS-127 with multiple emissions had significantly lower ejaculation latencies during copulatory tests conducted prior to drug treatment than animals which had no or only single seminal emissions following RDS-127 injection. Spontaneous seminal emission in the 3 day period initiated 2 hours after RDS-127 injection was unaffected by the drug. Spontaneously produced plugs were approximately twice the weight of those induced by RDS-127. In Experiment 3, seminal emission was induced in spinally transected rats 1.7 +/- 0.4 minutes following RDS-127 administration, whereas drug treatment attenuated the enhancement of penile reflexes observed following midthoracic spinal transection. These experiments suggest that a spinally-mediated dopaminergic mechanism is capable of stimulating seminal emission acutely in the rat and inhibiting the display of penile reflexes by the supine animal.

Animals↗
PubMed1982

Effects of a novel dopamine-receptor agonist RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane), on hormone levels and sexual behavior in the male rat.

Selective changes in the mating pattern occurred 30 minutes following administration of RDS-127 (3.0 mg/kg, IP) to sexually experienced adult male rats. Marked decreases in intromission frequency and ejaculation latency were observed. These data indicate a potent effect upon conummatory mechanisms underlying copulatory behavior. The lack of effect upon arousal state was further demonstrated utilizing a "mounting test" (in which the penis is anesthetized by topical application of tetracaine hydrochloride). No difference in mounting behavior was seen. Seminal plugs were noted in a large percentage of treated animals at the time of anesthetic application. Additionally, a six-fold decrease in plasma prolactin and a lesser decrement in plasma luteinizing hormone were evident. Finally, in sexually experienced castrate animals, RDS-127 induced mounting in two thirds and intromissive and ejaculatory patterns in one third of the treated animals, 35 days postcastration. These effects were greatly attenuated by 56 days postcastration. The selective alteration of consummatory mechanisms, with little or no effect upon arousal status, suggests a neurochemical separation of these two components in the intact male rat.

Animals↗
PubMed1982

Hormonal replacement and sexuality in men.

Only in the last few years has the scientific study of hormonal replacement therapy for hyposexuality begun in earnest with the advent of appropriately controlled experiment studies. Dose-response relationships can be demonstrated between testosterone (T) and sexual measures, but these have not yet been investigated in detail. Some aspects of sexual function are maintained in the presence of androgen levels well below the normal range, but preliminary evidence suggests that within a normal population high levels of T are correlated with more vigorous responses to visual erotic stimuli. Though T (and to a greater extent free T) declines with aging in parallel with the decline of sexual function, these hormonal changes contribute only to a minor extent to the behavioural change. Some non-aromatizable androgens may be less effective in stimulating sexual behaviour than T, but initial data on effects of dihydrotestosterone suggests that the capacity of an androgen to be aromatized (converted to oestrogen) is not a requirement for its sexual action. While T apparently increases the incidence of all types of male sexual activity, recent data contradict the belief that it directly facilitates the erectile mechanism in men, even though erection frequency is greatly reduced in untreated hypogonadal men. At the present juncture, it appears that the initial action of T may be on libido factors which lead in turn to the stimulation of other aspects of sexuality. Specifically, we propose that androgen acts through stimulating genital sensations and/or other pleasurable awareness of sexual response rather than directly through cognitive processes such as sexual imagery.

Adult↗
PubMed1982

The molecular aspects of elastin gene expression.

This report summarizes recent advances in the understanding of the molecular mechanisms which provide the basis for the regulation of elastin synthesis. Methods are available for the direct quantitation of elastin messenger RNA activity and absolute levels of elastin messenger RNA. Current evidence suggests, that at least for some systems, regulation of elastin synthesis primarily occurs at a pretranslational level. Recent advances in the cloning of elastin cDNA and elastin genes will permit the determination of elastin and elastin gene primary structure. These cloned elastin genes will also provide useful probes for the further analysis of the control of elastin gene expression in development and disease states.

Animals↗
PubMed1981

Modulation of tropoelastin production and elastin messenger ribonucleic acid activity in developing sheep lung.

During fetal development of the sheep lung, elastin content continually increases. For examination of the processes controlling this elastin accumulation, an explant culture system was characterized with respect to changes in tropoelastin production in sheep lung during fetal and early postnatal development. Relative tropoelastin production in cultured lung explants, quantitated by immunoprecipitation, was about 0.3% of total [14C] valine incorporation during the period from 55 to 104 days after conception. This percentage began to increase by 112 days after conception, reached a maximum value of about 1.0% by 135 days after conception, and then declined to 0.5% soon after birth. The absolute rate of tropoelastin production paralleled these changes in relative tropoelastin production. For evaluation of the processes controlling tropoelastin production in the developing sheep lung, total cellular RNA prepared from 68-day-old fetal, 107-day-old fetal, and 147-day-old fetal lung was translated in a rabbit reticulocyte lysate system. Elastin mRNA activity, expressed as the amount of elastin precursor translated per microgram per microgram of DNA, increased about 3-fold during fetal lung development, and elastin precursor synthesis, expressed as a proportion of total translational activity, increased in parallel. It appears, therefore, that elastin production in developing fetal lung is modulated, at least in part, by the amount of available translatable elastin mRNA present in the tissue.

Animals↗
PubMed1981

Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema.

This study suggests one mechanism by which alveolar macrophages accumulate in the lung in pulmonary emphysema: elastin fragments generated at the diseased sites are potent chemoattractants for monocytes, the precursors of the macrophages. The most chemotactic elastin fragments have a molecular weight between 10,000 and 50,000 and are active at concentrations as low as 3 nanograms per milliliter. By comparison, elastin fragments with higher molecular weights and desmosines are active at concentrations greater than 0.3 microgram per milliliter. In addition, preincubation of monocytes with the 10,000- to 50,000-dalton elastin impairs the ability of the cells to migrate toward elastin fragments but not toward activated serum. Fragments of tropoelastin are not chemotactic for monocytes. Because elastin, but not tropoelastin, contains lysyl-derived cross-links, these structures may be the active chemotactic site on the elastin fragments.

Cells, Cultured↗
PubMed1981

Endocrine and behavioral effects of continuous exposure of male rats to a potent luteinizing hormone-releasing hormone (LHRH) agonist: evidence for central nervous system actions of LHRH.

Continuous exposure of intact male rats to [6-D-(2-naphthyl)-alanine]LHRH, a highly potent LHRH agonist, diminished testis and pituitary weights and decreased basal plasma levels of testosterone and LH. In addition, treatment with this analog abolished the pituitary hypertrophy and LH hypersecretion normally associated with castration. Alterations of male sex behavior were also noted in these animals. Analog-treated intact rats showed longer intromission latencies and mount latencies in early tests and ceased to show sexual behavior 6-8 weeks after initiation of treatment. In addition, the gradual decline in behavior normally observed after castration was markedly accelerated by analog administration. Castrates bearing 5-mm Silastic testosterone-containing capsules which maintained copulatory performance displayed behavioral deficiencies when given the peptide. No significant effect of analog was noted in rats with 30-mm Silastic implants, which provide a higher level of testosterone replacement. Continuous analog treatment promotes endocrine effects consistent with complete antagonism of the effects of endogenous LHRH. The behavioral disruption associated with this manipulation suggests a role for endogenous LHRH in maintaining sex behavior in a low testosterone environment.

Animals↗
PubMed1981

Developmental regulation of elastin synthesis.

The regulation of elastin production has been evaluated and compared in two systems in the developing sheep: nuchal ligament and lung. Absolute rates of production in explant culture were estimated by immunoprecipitation of newly synthesized elastin and determination of precursor pool specific activities. Lung elastin production increased about 2.5-fold while nuchal ligament production increased about 9-fold during the latter half of gestation. In comparison, the activities of elastin messenger RNA(mRNAE) of these tissues were determined in a cell-free system by immunoprecipitation. The increases in mRNAE activity largely paralleled the rises in elastin production, suggesting that elastin synthesis in these tissues is regulated, at least in part, by the availability of translationally active mRNAE.

Aging↗
PubMed1980

Effects of centrifugation stress on pituitary-gonadal function in male rats.

The effects of centrifugation for various lengths of time were investigated on circulating levels of luteinizing hormone (LH) and testosterone in male rats. In a chronic 52-day experiment, centrifugation at 4.1 G significantly reduced LH and testosterone levels for the entire period. Centrifugation at 2.3 G had less effect inasmuch as LH levels were not significantly decreased and testosterone levels were significantly reduced only during the first few days of centrifugation. In more acute experiments, centrifugation at 4.1 G for 4 h resulted in reduced testosterone levels, whereas centrifugation for 15 min did not significantly alter the hormone levels. These results indicate that centrifugation can decrease circulating LH and testosterone levels if the gravitational force is of sufficient magnitude and is maintained for a period of hours. Chronic centrifugation may also inhibit the acute excitatory response of LH to handling and ether stress.

Animals↗
PubMed1980

Gonadotropin regulation in middle-aged male rats.

Gonadotropin regulation was compared in middle-aged (13 months old) and young adult (3 months old) male rats. Two experiments were conducted on castrated animals given testosterone in Silastic capsules; the dimensions were adjusted to insure equivalent circulating testosterone levels in the two age groups, as validated by RIA. Plasma LH and FSH were also measured by RIA. In Exp 1, each animal was implanted immediately after castration with multiple capsules sufficient to maintain tonic suppression of LH. One capsule was removed each week, thereby reducing testosterone levels in 0.4 ng/ml steps, in order to determine the testosterone level (threshold) at which LH is released from tonic suppression. Middle-aged animals had a threshold 50% lower than young animals, requiring much less testosterone to maintain tonic LH levels. They also showed an attenuated rise in LH and FSH after release from tonic suppression. In Exp 2, long term castrates were given capsules which produced plasma testosterone levels of approximately 1.5 ng/ml in order to evaluate the negative feedback effects of testosterone on elevated LH levels. The testosterone was more effective in suppressing LH in middle-aged rats than in young animals. These results indicate that: 1) middle-aged male rats develop an increased sensitivity to the feedback effects of testosterone, and this increased sensitivity is operative within the normal physiological range of LH and testosterone; and 2) middle-aged animals have a reduced capacity to increase LH and FSH levels after release from tonic suppression. These changes in gonadotropin regulation can account, to a large extent, for the pituitary-testicular decline which develops during middle age in male rats.

Aging↗
PubMed1979

Procollagen processing. Limited proteolysis of COOH-terminal extension peptides by a cathepsin-like protease secreted by tendon fibroblasts.

An enzymatic activity, capable of removing the COOH-terminal extensions of type I chick procollagen, has been demonstrated in embryonic chick tendons and in cultured tendon fibroblasts utilizing two new methods of analysis. The protease was purified by a combination of ultrafiltration concanavalin A affinity chromatography and gel filtration. The isolated protein has an apparent Mr of 43,000 by gel filtration and sodium dodecyl sulfate gel electrophoresis. The enzyme shows a major pH optimum at 4.2 and is susceptible to inhibitors such as pepstatin and leupeptin; it therefore seems related to the cathepsins. The possibility that this enzyme plays a role in the limited proteolytic processing of procollagen is discussed.

Animals↗