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J M Davidson

Publications and source records attributed to J M Davidson.

At least 127 records · Page 7Linked to original sources
PubMed1987

Plasma oxytocin increases in the human sexual response.

The purpose of this study was to determine whether plasma oxytocin (OT) levels change during human sexual responses and, if so, to demonstrate the temporal pattern of change. Plasma OT levels were measured by RIA before, during, and after private self-stimulation to orgasm in normal men (n = 9) and women (n = 13). Blood samples were collected continuously through indwelling venous catheters. The subjects pressed a signal to indicate the start and finish of orgasm/ejaculation. Objective assessment of sexual arousal and orgasm was obtained by measuring blood-pulse amplitude and electromyographic activity, recorded continuously throughout testing from an anal device containing a photoplethysmograph and electromyograph electrodes connected to a polygraph located in an adjacent room. These measures allowed collection of data from men and women of changes in blood flow and muscle activity in the lower pelvic/pubic area. Plasma OT levels increased during sexual arousal in both women and men and were significantly higher during orgasm/ejaculation than during prior baseline testing. We suggest that the temporal pattern of secretion could be related to smooth muscle contractions of the reproductive system during orgasm.

Adult↗
PubMed1986

Developmental changes in collagen and elastin biosynthesis in the porcine aorta.

Elastin and collagen are the principal scleroproteins of the aortic wall, and they largely determine its physical and mechanical properties. During perinatal development of the aorta, elastin and collagen accumulate rapidly, being present as inverse gradients by the time of birth. Elastin is most prevalent in the thoracic aorta, decreasing distally, while collagen shows the opposite trend. The present studies have determined the relative and absolute rates of collagen and elastin synthesis in the porcine aorta between 60 days of fetal development (mid-gestation) and 110 days after birth. Although there was measurable elastin synthesis in the upper thoracic aorta at the earliest time evaluated, there was a fourfold increase in relative elastin synthesis (from 4 to 16% of total protein synthesis) between 60 fetal days and birth. Elastin synthesis was maximal in successively distal segments between 1 and 3 weeks after birth. Relative collagen synthesis progressively increased in distal aortic regions between 90 fetal days and 60 days postpartum. Greater than twofold increases over thoracic levels were measured. Both elastin and collagen synthesis largely subsided by 110 days of development. When expressed as absolute rates of protein synthesis, these scleroproteins were maximally expressed in the first 3 postnatal weeks. Elastin mRNA levels were determined with a cloned sheep gene fragment by molecular hybridization. Gradients of elastin message were present at 60 fetal days and at 4 and 14 days after birth, elastin mRNA levels being maximal in the upper thoracic aorta at 14 days after birth. The differentiation of the aortic wall thus follows discrete patterns of phenotypic change which may be coupled to the rheologic stresses accompanying development of the circulatory system.

Age Factors↗
PubMed1986

Differential interactions of "prosexual" drugs with 5-hydroxytryptamine1A and alpha 2-adrenergic receptors.

Radioligand binding studies were used to analyze the interactions of six "prosexual" drugs with 5-hydroxytryptamine1A (5-HT1A) and alpha 2-adrenergic receptors in rat brain membranes. Three drugs that facilitate seminal emissions and/or ejaculations [8-hydroxy-2-n-propylaminotetralin (8-OH-DPAT), 5-methoxy-dimethyltryptamine, and RDS-127] are potent and selective inhibitors of [3H]8-OH-DPAT binding to 5-HT1A receptors. By contrast, three drugs with primary sexual arousal effects (yohimbine, imiloxan, and idazoxan), are potent agents at alpha 2-adrenergic receptors labeled by [3H]yohimbine. These data suggest that radioligand binding analysis of prosexual agents may elucidate the pathophysiology of sexual behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Elastin production in human skin fibroblast cultures and its decline with age.

Recent studies have established that cultured human skin fibroblasts secrete the soluble precursor of elastin, tropoelastin (TE). The present studies evaluate, by an enzyme-linked immunosorbent assay, the stability of the TE phenotype and the effect of culture conditions and donor age on TE accumulation by human skin fibroblasts. Tropoelastin was maximally produced by 2 control fibroblast strains at early confluency (32-49 X 10(3) molecules/cell/h), and its serum-dependent accumulation in the medium was linear for at least 72 h. Inhibition of cross-linking had no effect on the rate of elastin production. Optimum serum concentrations for TE production differed for fibroblast cell strains derived from foreskin and trunk skin fibroblasts. Production of TE by human skin fibroblasts was stable through nearly 30 population doublings after which there was a greater than 2-fold decline in the rate of accumulation. In a cohort of donor strains, TE production appeared to decline at donor ages greater than or equal to 70 years. Under standard culture conditions, cell strains from normal donors of various ages produced TE at rates ranging from 25-69 X 10(3) molecules/cell/h. Rates of TE accumulation in medium were not significantly altered by degradation of TE, as a variety of cell strains tested exhibited minimal cell-associated elastolytic activity. Based on the demonstration of a stable elastin phenotype, skin fibroblast cultures provide a new system for studying regulation of elastin biosynthesis and evaluating potential defects in elastin metabolism associated with certain connective tissue disorders.

Adolescent↗
PubMed1985

Stimulation of spinal serotonergic receptors facilitates seminal emission and suppresses penile erectile reflexes.

Penile erection and ejaculation are produced by spinal reflexes subject to tonic control from the brain. This study examines the possible involvement of serotonergic transmission in the supraspinal modulation of such reflexes. The effects of two drugs which facilitate serotonergic transmission by different mechanisms, namely the direct receptor agonist, 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), and the reuptake inhibitor, zimelidine, were compared in intact and spinal rats. Results show that serotonergic stimulation in intact rats by either drug produces a dose-related increase in the incidence of seminal emission as well as a definite decrease of the display of erectile responses. In the spinal animals 5-MeODMT treatment reproduced both effects. By contrast, zimelidine, which needs functional nerve endings to exert its agonistic action, was ineffective in the spinal rats. This is interpreted to exclude a peripheral mechanism for the effects of the serotonin agonists on penile reflexes of intact animals and makes a strong case for a spinal site of action. We postulate the existence of serotonergic receptors located in the lower segments of the spinal cord which, when stimulated, trigger seminal emission and suppress erection.

Animals↗
PubMed1985

Longitudinal gradients of collagen and elastin gene expression in the porcine aorta.

The physical and chemical properties of the mammalian aorta are known to vary as a function of distance from the heart. These properties are highly dependent collagen and elastic fibers. In order to evaluate the mechanisms which regulate the accumulation of these two connective tissue proteins, gene expression was evaluated at both the biosynthetic and messenger RNA levels. Short-term (3 h) explant cultures of the medial portion of four segments of the descending aorta in newborn pigs were incubated in the presence of [3H] proline. Collagen production was quantified by collagenase digestion and elastin production was determined by immunoprecipitation. Between the conus arteriosus and the bifurcation of the iliac arteries, relative collagen synthesis increased 2-fold (from 5.8 to 12.0% of total protein synthesis), while relative elastin synthesis declined 10-fold (from 16.4 to 1.6% of total protein synthesis). Similarly, collagen production increased more than 7-fold (from 6.7 to 49.8 X 10(3) molecules/cell/h) while elastin production was reduced more than 3-fold (from 71.8 to 21.0 X 10(3) molecules/cell/h) along this developmental gradient. Elastin synthesis appeared to be controlled to a significant extent by the availability of elastin mRNA, since both cell-free translation and molecular hybridization to a cloned elastin gene probe showed gradients of elastin gene expression. Similarly, collagen synthesis was apparently regulated, at least in part, by an inverse gradient of collagen mRNA, as measured with a cloned cDNA for the pro-alpha 1(I) collagen gene. Marked changes in the amount of non-elastin protein synthesis accompanied differentiation and accounted for larger changes in relative synthesis. These results suggest that the phenotype of the cells of the porcine artery wall is distinct in different regions of this organ at this developmental stage.

Aging↗
PubMed1985

Effects of estrogen treatment on sexual behavior in male-to-female transsexuals: experimental and clinical observations.

The effects of oral estrogen treatment on sexual physiology and behavior were examined in seven presurgical male-to-female transsexuals engaged in cross-living. Subjects were studied prior to hormone treatment, during long-term hormone treatment, and during an experimental double-blind period in which the effects of their usual hormone regimen were compared to those of placebo during successive 4-week periods. Subjects maintained daily logs of their spontaneous erections, sexual activity (masturbation), and feelings throughout the study. Nocturnal penile tumescence was measured, using home monitors, in order to estimate estrogen-induced changes in erectile capacity. Erectile response to sexually arousing stimuli (erotic films and self-generated fantasy) was also assessed in the laboratory. Blood samples were taken at intervals for testosterone and sex-hormone-binding globulin measurements and free testosterone levels were calculated. Estrogen treatment inhibited sexual activity, spontaneous erections, and nocturnal penile tumescence. No significant effects on psychophysiological response to film and fantasy or frequency of sexual feelings were found, but the psychophysiological data were very variable. Testosterone levels were suppressed by estrogen, but not to the extent that free testosterone levels were. It appears that declining free testosterone level is associated with inhibition of spontaneous erections (during both sleep and waking) and of sexual activity, though the latter relationship is less clear. No evidence of an effect on film or fantasy-induced erections was obtained.

Adult↗
PubMed1985

Relationships among sexual behavior, hot flashes, and hormone levels in perimenopausal women.

Forty-three perimenopausal women kept daily records of menstrual cycles and sexual activity. Data on hot flashes and plasma estradiol and testosterone levels were obtained at two points during the menopausal transition. The prospective data yielded a significant negative association between hot flash ratings and regularity of sexual intercourse at both time points. A significant negative correlation was found between estradiol (in the early part of the cycle) and hot flashes ratings at the first data point only, and positive correlations were found between hot flashes and ratio of testosterone to estradiol (T/E) at both. Frequency of sexual intercourse and level of plasma estradiol were higher, and T/E and hot flash ratings were lower in "early" perimenopausal women who were still having cycles at least once every 30 days, as compared with "late" perimenopausal women who were cycling less often. It was concluded that a close association exists between increasing irregularity of menstrual cycles, hot flashes, declining estradiol levels, and declining frequency of intercourse during the perimenopause. Causal relationships remain to be established.

Adult↗
PubMed1985

Analysis of the 3' region of the sheep elastin gene.

The nucleotide sequences of a 1279-bp sheep elastin cDNA clone, pcSEL1 [Yoon et al. (1984) Biochem. Biophys. Res. Commun. 118, 261-269], and a 1230-bp sheep elastin genomic subclone, pSS1 [Davidson et al. (1984) Biochem. J. 220, 643-652], corresponding to a portion of the cDNA clone, were determined. These analyses permitted determination of the 100 amino acids at the carboxy terminus of sheep tropoelastin. A portion of this sequence showed strong homology to known sequences of pig tropoelastin, but most of the sequence had not been previously determined through protein sequencing. Novel aspects of the tropoelastin molecule which have been revealed by the present analyses are (i) the presence of an unusual sequence, KPPKP, which may contribute to crosslink formation; and (ii) the finding of cysteine within a sequence, CLGKSCGRKRK, at the putative carboxy terminus of tropoelastin. Because of the presence of these sequences, it is speculated that the carboxy-terminal region may be of importance in crosslinking tropoelastin molecules to themselves or to other matrix macromolecules. The nucleotide analyses revealed that sheep elastin mRNA contains a 974-bp untranslated sequence at the 3' end, which appears to be strongly conserved among species.

Animals↗
PubMed1985

Testosterone is not required for the enhancement of sexual motivation by yohimbine.

Yohimbine HCL (2 mg/kg, 20 min prior to testing) administration was followed by significant decreases in the latencies to initial mount, intromission and ejaculation in castrated male rats bearing 2 mm testosterone-containing Silastic capsules 51 days after castration. Further, yohimbine stimulated copulatory activity in castrated, nonhormone-treated male rats up to 91 days after castration. Finally, yohimbine induced mounting in intact, nonreceptive female rats. These observations indicate that testosterone is not required for the enhancement of sexual motivation by yohimbine and support the suggestion that alpha 2-adrenoceptors are involved in the modulation of sexual arousal.

Animals↗
PubMed1985

Reproductive physiology and behavior in the male rat following acute and chronic peripheral adrenergic depletion by guanethidine.

The effect of guanethidine, an adrenergic neuron blocking agent, on sexual behavior, penile reflexes, and spontaneous seminal emission (SSE) in the rat was studied by acute (i.e., 4 hours prior to testing) and daily IP injection of a low (5 mg/kg) and moderately high (25 mg/kg) dose of the drug. Acute low dose treatment eliminated the expulsion of a seminal plug with behavioral ejaculation without affecting sexual behavior; while acute high dose administration significantly decreased the number of intromissions preceding ejaculation and eliminated emission in copula and SSE for 3 days, with no evidence of retrograde ejaculation. Acute high dose treatment also increased the number of long flips displayed in the penile reflex test, and resulted in significant depression in plasma testosterone (T) and luteinizing hormone (LH) levels. Daily injection with the low dose eliminated emission in and ex copula for 4 weeks, without altering sexual behavior or penile reflexes. Seminal emission in copula reappeared more rapidly after stopping injections than SSE. Chronic high dose treatment was also without effect on copulatory activity. There was a partial recovery of emission in copula by the fourth week of treatment, suggesting that a nonadrenergic mechanism had assumed this function. In penile reflex tests conducted after 4 and 8 weeks, significantly fewer erections were displayed by drug-treated animals. During the period of initial recovery of emission in copula, emission during the reflex test was markedly increased, but SSE was decreased. Plasma T was significantly suppressed after two and four weeks of daily injections, but not thereafter, while plasma LH levels were not affected by the drug.

Animals↗
PubMed1985

Central effects of RDS-127: sexual behavior after intracerebroventricular administration and in vitro receptor binding studies.

RDS-127, in a dose-related manner, induced seminal emission ex copula after intracerebroventricular (i.c.v.) administration. In mating tests initiated 6 min after i.c.v. administration, RDS-127 induced decreases in ejaculation latency and intromission frequency, with some rats ejaculating on the initial intromission. Additionally, penile reflexes were eliminated by 150 micrograms and 600 micrograms, but not by an intermediate dose. In in vitro radioligand binding studies, RDS-127 potently displaced [3H]DPAT binding to 5-HT1A sites in rat cortex (Ki = 14 +/- 4 nM) and was only moderately effective in displacing [3H]spiperone binding to dopaminergic D2 sites in rat striatum. RDS-127 was essentially ineffective at 5-HT1B sites labeled by [3H]5-HT in rat striatum (Ki = 13 000 +/- 4 000 nM). These data demonstrate that centrally administered RDS-127 mimics the previously reported alterations in sexual behavior after systemic treatment and that RDS-127 is a high affinity 5-HT1A agent with low affinity at the 5-HT1B binding site.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

A longitudinal study of the effects of menopause on sexuality.

From an initial group of 39, 16 cycling peri-menopausal women completed a longitudinal study in which they recorded menstrual and sexual behavior daily and were interviewed at roughly 4-mth intervals until 1 yr or more without cycling. At each interview women gave 20-ml blood samples, completed sexuality questionnaires, and rated themselves for menopausal symptoms. As predicted, the difference in weekly rate of sexual intercourse before and after the cycle showed a significant decline (P less than 0.05). For each subject, mean weekly rates of sexual intercourse for 13-wk periods over the entire transition period were plotted and the slope of the line was calculated. Overall, the mean slope was negative, as predicted, and was significantly different from zero (P less than 0.05). The questionnaire data showed that compared with their pre-menopause data, the women had fewer sexual thoughts or fantasies (P less than 0.01), suffered more from lack of vaginal lubrication during sex (P less than 0.01), and were less satisfied with their partners as lovers (P less than 0.05) after menopause. While estradiol (E) and testosterone (T) levels showed significant declines (P less than 0.02), testosterone showed the most consistent association with coital frequency. The findings generally supported our initial hypothesis of a decline in sexual interest and coital frequency after menopause.

Coitus↗
PubMed1985

Sustained release of epidermal growth factor accelerates wound repair.

Epidermal growth factor (EGF) is a potent mitogen in vitro, but its biological role is less clear. The vulnerary effects of EGF were evaluated in a model of wound repair, the polyvinyl alcohol sponge implanted subcutaneously in rats. EGF was purified to homogeneity by reverse-phase HPLC and quantified by receptor binding assay and amino acid analysis. Preliminary data showed moderate promotion of granulation tissue formation by daily injections of 10 micrograms of EGF. To test the hypothesis that long-term exposure to EGF is required for complete cellular response, the factor was incorporated into pellets releasing 10 or 20 micrograms of biologically active EGF per day, and the pellets were embedded within the sponges. Slow release of EGF caused a dramatic increase in the extent and organization of the granulation tissue at day 7, a doubling in the DNA content, and 33% increases in protein content and wet weight, as compared with placebo controls. Although collagen content was also increased by almost 50%, the relative rate of collagen synthesis remained the same, suggesting that the morphological and biochemical increase in collagen resulted from increased numbers of fibroblasts rather than a specific stimulation of collagen synthesis. These results indicate that the local sustained presence of EGF accelerates the process of wound repair, specifically neovascularization, organization by fibroblasts, and accumulation of collagen.

Animals↗
PubMed1985

Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor.

Cartilage-derived growth factor (CDGF), a cationic polypeptide of approximately 18,000 mol wt, was prepared from bovine articular cartilage; other sources were bovine and human scapular and costal cartilage. Previous studies have shown that CDGF stimulates the proliferation of cultured mouse fibroblasts as well as chondrocytes and endothelial cells from various sources. In this study, CDGF was shown to stimulate dose-dependently the accumulation of DNA and collagen by rat embryo fibroblasts and a population of fibroblasts derived from granulation tissue. CDGF also stimulated the proliferation of cultured bovine capillary endothelial cells dose-dependently. To evaluate the effects of CDGF in vivo, we implanted polyvinyl alcohol sponges subcutaneously in rats. 6 d postimplantation, sponges were injected with 300 micrograms of partially purified CDGF, a dose which takes into account the cell numbers in the sponges as compared with cell cultures. CDGF rapidly disappeared from the sponges and only approximately 10% of the initial dose was present at 4 h. Despite its transient presence, CDGF caused a relative increase in sponge DNA content of 2.6-fold at 48 h and 2.4-fold at 72 h. We repeated the sponge experiment by using 500-ng injections of CDGF purified to near homogeneity by heparin-Sepharose chromatography. Purified CDGF caused significant increases in sponge collagen, protein, and DNA content at 48 and 72 h after a single injection. The effects of CDGF were abolished by heat and unaffected by reduction of disulfide linkages. Morphologically, CDGF did not evoke an inflammatory response, and its effect on proliferating endothelial cells and fibroblasts was, therefore, probably direct. However, increases in DNA content of sponges could not be fully accounted for by increased DNA synthesis, which suggests that recruitment may be an important component of the in vivo response. Taken together, the effects of CDGF on cultured cells and granulation tissue suggest that the sustained presence of CDGF in vivo may greatly enhance its effects upon wound repair.

Animals↗
PubMed1985

Blockage of tropoelastin secretion by monensin represses tropoelastin synthesis at a pretranslational level in rat smooth muscle cells.

The blockage of protein secretion in the R22 cultured rat aortic smooth muscle cell strain with monensin repressed tropoelastin gene expression at the mRNA level by ca. 50-fold as measured by biosynthetic pulse-labeling, in vitro translation, and hybridization with a tropoelastin genomic DNA probe. These results suggest that tropoelastin gene expression is autoregulated, and they represent the first reported effect of monensin on gene expression.

Animals↗
PubMed1985

Evidence for the modulation of sexual behavior by alpha-adrenoceptors in male rats.

Clonidine, a commonly used antihypertensive agent believed to act by stimulation of central alpha-adrenoceptors, produced a dose-related suppression of ejaculatory behavior in sexually vigorous male rats throughout the range of treatment (0.0125-0.5 mg/kg). Treatment with 0.25 mg/kg virtually eliminated ejaculatory behavior, without altering the number of animals mounting and intromitting. These effects were maintained for at least 4 h after treatment. Prazosin, another antihypertensive (but acting by blockade of alpha 1-adrenoceptors), increased latencies to initiation of copulation, to ejaculation, and to reinstatement of copulation following ejaculation. Additionally, prazosin (1 mg/kg) pretreatment failed to attenuate or prevent the clonidine-induced suppression of ejaculation. In contrast, yohimbine, a drug which preferentially blocks alpha 2-adrenoceptors (2 mg/kg, 20 min prior to mating tests), caused a facilitation of copulatory behavior as evidenced by drastic decreases in ejaculation latency and intercopulatory and postejaculatory intervals. Pretreatment with yohimbine completely prevented the clonidine-induced suppression of ejaculation, while clonidine attenuated the facilitatory effects of yohimbine, suggesting a competitive interaction. These data lead to the suggestion that increased excitatory adrenergic activity results in increased sexual arousal either by blockade of alpha 2-or stimulation of alpha 1-adrenoceptors. Alternatively, stimulation of alpha 2-or blockade of alpha 1-adrenoceptors results in diminished sexual motivation. While the precise implications of this animal research for the clinic are as yet unclear, further research could lead to important developments in the pharmacological treatment of sexual dysfunctions.

Animals↗