Showing papers by "Worcester Foundation for Biomedical Research published in 1978"
TL;DR: In seven men the mean +/- SE value for the fractional conversion of androstene tissue was 0.0007 +/-0.0001 for muscle and 0.0012 +/- 0.0002 for adipose tissue, both of these values were significantly less than the respective values of and Frostenedione aromatization to estrone.
Abstract: [7-3H]Androstenedione and [4-14C]es-trone or [7-3H]testosterone and [14C]estradiol were infused at constant rates into brachial arm veins of 15 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle, and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In seven men the mean ± SE value for the fractional conversion of androstenedione to estrone was 0.013 ± 0.004 for muscle and 0.014 ± 0.002 for adipose tissue. In eight men the mean SEvalue for the frac-tional conversion of testosterone to estradiol was 0.0007± 0.0001 for muscle and 0.0012 ± 0.0002 for adipose tissue. Both of these values were significantly (P < 0.01) less than the respective values of androstenedione aromatization to estrone. If constancy of tissue aromatization throughout the body is assumed, the muscle accounts for 25-30% and adipose tissue for 10-15% of the total extragonadal aromatization of androgens to estrogens. (J Cli...
391 citations
TL;DR: Several brain areas showing the most drastic residua of early protein malnutrition are pinpointed and are beginning, by use of morphometric, electro-ontogenetic, biochemical development and behavioral studies, to define brain locales and basic mechanisms by which these insults produce their effects.
329 citations
TL;DR: The results support the notion of two anatomically distinct olfactory systems and demonstrate two previously unreported pathways through which the limbic system may modulate sensory processing in the Olfactory bulb.
271 citations
TL;DR: The possible involvement of mono-oxygenase in biotransformation in methoxychlor into estrogenic metabolites in vivo is discussed and the demethylated products were resolved by thin-layer chromatography into three chromatographically distinct components more polar than methoxy chlor.
223 citations
TL;DR: The notion that olfactory bulb interneurons may be assigned to two functional groups associated with two distinct levels of integration is discussed in relation to the notion thatOlfactory bulbs may be assign to twofunctional groups associatedwith two distinct level of integration.
201 citations
TL;DR: The review suggests that the regulation of testicular steroidogenesis depends on a complex of adenohypopyhseal hormones that FSH and PRL are both important components of this complex and that steroidogenesis regulation in the testis resembles steroidogenesis Regulation in the ovary.
Abstract: The action of pituitary hormones on testicular steroidogenesis is reviewed with particular focus on follicle stimulating hormone (FSH) and prolactin (PRL). Production of androgens by the testis depends on luteinizing hormone (LH) and the action of LH on the Leydig cells. There is evidence that FSH augments the action of LH on plasma testosterone (T) levels and on the growth of androgen-dependent male accessory reproductive glands. During sexual maturation FSH has a physiological role in increasing the responsiveness of the testes to LH stimulation. PRL augments the effect of endogenous or exogenous LH on testicular steriodogenesis. The effects of PRL seem to indicate direct action on the Leydig cells. PRL also seems to increase stores of cholesterol ester to provide a pool of precursors for steroidogenesis. PRL may be very important in sexual maturation. The review suggests that the regulation of testicular steroidogenesis depends on a complex of adenohypopyhseal hormones that FSH and PRL are both important components of this complex and that steroidogenesis regulation in the testis resembles steroidogenesis regulation in the ovary.
110 citations
TL;DR: Depressed men and women who fail to respond to conventional antidepressant treatment show significant alleviation of depressive symptoms when treated with high doses of gonadal steroids, suggesting that depression in men is accompanied by a high production of estradiol and women are accompanied by higher production of testosterone.
Abstract: 1. 1. Depressed men and women who fail to respond to conventional antidepressant treatment show significant alleviation of depressive symptoms when treated with high doses of gonadal steroids (conjugated oral estrogen in women; mesterolone in men). 2. 2. Depression in men is accompanied by a high production of estradiol; and depression in women is accompanied by higher production of testosterone. Whether these findings are related to the therapeutic effects of gonadal hormones upon depression are unknown.
82 citations
TL;DR: It was concluded that laboratory grade methoxychlor contained a contaminant that was potentially estrogenic and suggested an extremely high affinity for uterine cytosolic E2 receptors.
Abstract: Laboratory grade methoxychlor (99% pure), base-washed methoxychlor, and a metabolite of methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), were tested for their ability to compete with [3 H] estradiol-17 beta ([3 H]E2) for specific binding to the estrogen receptor from immature rat uterine cytosol. The binding was determined on 10--30% sucrose gradients and by a dextran-coated charcoal assay and subsequent Scatchard plot analysis. On gradients, laboratory grade methoxychlor, but not base-washed methoxychlor, suppressed [3 H]E2 binding to the 8S estrogen receptor. However, the base-soluble fraction from washing of laboratory grade methoxychlor caused suppression o[3 H]E2 binding on sucrose gradients at a concentration as low as 3.6 ppm. Scatchard plot analysis indicated that the inhibition of binding observed with laboratory grade methoxychlor was competitive in nature and not caused by receptor destruction. It was concluded that laboratory grade methoxychlor contained a contaminant that was potentially estrogenic. HPTE, an in vivo metabolite of methoxychlor, caused a marked suppression of [3 H]E2 binding in the 85 region of the gradients. Analysis by Scatchard plot indicated that the effect of HPTE was not to decrease the number of E2 binding sites but merely to alter the affinity of binding to the receptor, presumably in a competitive manner. The low K1 value for HPTE suggested an extremely high affinity for uterine cytosolic E2 receptors.
76 citations
TL;DR: It appears that the THC-induced reduction in plasma T levels observed in vivo is due to an inhibition of pituitary LH release, and to a direct effect on the testicular responsiveness to LH stimulation, and the reduction in copulatory behavior observed after acute exposure to THC may be secondary to a reduction in peripheral T concentration.
Abstract: In mouse testes incubated with hCG, addition of Δ 9 -tetrahydrocannabinol (THC) resulted in a significant inhibition in the accumulation of testosterone (T) and progesterone. The concentrations of 17α-OH progesterone, androstenedione, and estradiol were not changed. The inhibition of T production in this in vitro system by THC was dependent upon the presence of hCG in the medium, suggesting that THC may interfere with gonadotropin stimulation of testicular steroidogenesis. In contrast, suppression of T secretion by cannabinol (CBN) also occurred in the absence of hCG. In the in vivo studies, administration of a single oral dose of THC to adult male mice resulted in a reduction in plasma T, LH and FSH levels, as well as an increase in the concentration of esterified cholesterol in the testis. In contrast, a single dose of CBN produced no significant changes in either plasma T or gonadotropin levels. Treatment with THC, but not with CBN, resulted in a pronounced reduction in the level of copulatory activity in adult male mice. It appears that the THC-induced reduction in plasma T levels observed in vivo is due to an inhibition of pituitary LH release, and to a direct effect on the testicular responsiveness to LH stimulation. The reduction in copulatory behavior observed after acute exposure to THC may be secondary to a reduction in peripheral T concentration.
75 citations
TL;DR: The current review focuses on the inheritance and expression of chicken genes that code for avian leukosis sarcoma virus (ALSVs) or viral products, referred to as endogenous viral genes.
Abstract: Three different groups of avian C-type viruses have been shown to contain RNA-directed DNA polymerases (Table 1). Each of these groups has characteristic but unrelated RNA, structural proteins, and reverse transcriptase (Halpern et al., 1973; Mizutani and Temin, 1973; Kang and Temin, 1973; Moelling et al., 1975; Hanafusa, T. et al., 1976). The genetic information for these viruses is found in viral RNA as well as in cellular DNA. The current review focuses on the inheritance and expression of chicken genes that code for avian leukosis sarcoma virus (ALSVs) or viral products. These cellular genes will be referred to as endogenous viral genes. Viral genes that are carried in virus and introduced into cells by infection will be referred to as exogenous viral genes.
70 citations
TL;DR: Treatment of HeLa cells in suspension culture with [14C]arachidonic acid led to a rapid incorporation of this fatty acid into cellular phospholipid pools, which could have direct effects on cell membrane structure and alter the biosynthesis of prostaglandins and related metabolites of arachidsonic acid.
TL;DR: Zona-free eggs were introduced to fresh or preincubated sperm suspensions and the penetration of eggs by foreign spermatozoa was examined, as evidenced by enlargement of the sperm head and formation of the male pronucleus.
Abstract: Zona-free eggs were introduced to fresh or preincubated sperm suspensions and the penetration of eggs by foreign spermatozoa was examined, as evidenced by enlargement of the sperm head and formation of the male pronucleus. It was found that zona-free hamster eggs can be penetrated by guinea-pig, deer mouse and rabbit spermatozoa but zona-free rat, mouse and rabbit eggs cannot be penetrated by guinea-pig spermatozoa. Furthermore, zona-free rat and mouse eggs cannot be penetrated by spermatozoa from two species of deer mice and the Mongolian gerbil. The zona pellucida of a few intact rat eggs can be penetrated by mouse (6%) and by P. leucopus spermatozoa (14%) but enlargement of the sperm head and formation of pronuclei were observed in the former but not in the latter. It seems that (1) sperm capacitation is required for the penetration of zona-free eggs, (2) the attachment of foreign spermatozoa to eggs may indicate their potential ability of penetration in some cases, (3) there is a certain affinity between the vitellus of one species and spermatozoa from another species, (4) the block to the entry of foreign spermatozoa is not only in the zona pellucida but also in the vitelline membrane, (5) zona-free hamster eggs can be penetrated by spermatozoa of six species, (6) mouse spermatozoa can penetrate zona-free eggs of three species, and (7) fertilization of intact P. maniculatus eggs can be achieved in vitro.
TL;DR: It is speculated that spectrin phosphorylation state may be regulated 1) by metabolic intermediates and other internal chemical signals that modulate kinase and phosphatase activities per se or determine their intracellular localization and 2) by membrane deformation that alters enzyme-spectrin interaction locally.
Abstract: The phosphorylation of spectrin polypeptide 2 is thought to be involved in the metabolically dependent regulation of red cell shape and deformability. Spectrin phosphorylation is not affected by cAMP. The reaction in isolated membranes resembles the cAMP-independent, salt-stimulated phosphorylation of an exogenous substrate, casein, by enzyme(s) present both in isolated membranes and cytoplasmic extracts. Spectrin kinase is selectively eluted from membranes by 0.5 M NaCl and co-fractionates with eluted casein kinase. Phosphorylation of band 3 in the membrane is inhibited by salt, but the band 3 kinase is otherwise indistinguishable operationally from spectrin kinase. The membrane-bound casein (spectrin) kinase is not eluted efficiently with spectrin at low ionic strength; about 80% of the activity is apparently bound at sites (perhaps on or near band 3) other than spectrin. Partitioning of casein kinase between cytoplasm and membrane is metabolically dependent; the proportion of casein kinase on the membrane can range from 25% to 75%, but for fresh cells is normally about 40%. Dephosphorylation of phosphorylated spectrin has not been studied intensively. Slow release of 32Pi from [32P] spectrin on the membrane can be demonstrated, but phosphatase activity measured against solubilized [32P] spectrin is concentrated in the cytoplasm. The crude cytoplasmic phosphospectrin phosphatase is inhibited by various anions – notably, ATP and 2,3-DPG at physiological concentrations. Regulation of spectrin phosphorylation in intact cells has not been studied. We speculate that spectrin phosphorylation state may be regulated (1) by metabolic intermediates and other internal chemical signals that modulate kinase and phosphatase activities per se or determine their intracellular localization and (2) by membrane deformation that alters enzyme–spectrin interaction locally. Progress in the isolation and characterization of spectrin kinase and phosphospectrin phosphatase should lead to the resolution of major questions raised by previous work: the relationships between membrane-bound and cytoplasmic forms of the enzymes, the nature of their physical interactions with the membrane, and the regulation of their activities in defined cell-free systems.
TL;DR: The presence of small amounts of dimethyl disulfide can account for much of the ability of whole vaginal discharge to attract males to the odor source even when this compound is assayed in the presence of large amounts of inactive biological odorants.
TL;DR: Although hnRNA has an overall ribonucleoprotein structure, the double-stranded regions have a particularly protein-free and accessible organization within the hnRNP particle, in which some regions of hn RNA are much more extensively complexed with protein than others.
TL;DR: A novel method of directly determining both the phases of the X-ray reflections and an absolute electron density scale is described, and how the method has been successfully tested on lecithin/cholesterol bilayers.
Abstract: THE principal aim in X-ray diffraction studies of biological membranes and lipid bilayers is to determine the electron density profile across the membrane and to interpret this in terms of the distribution of the component molecules. The derivation of such electron density profiles requires a knowledge of both the amplitudes of the X-ray reflections and their corresponding phase angles. Although the relative amplitudes can be easily determined from a diffraction pattern, the phases of the reflections cannot be directly observed. The determination of these phases has proved to be one of the most difficult and contentious aspects of the membrane diffraction field1–9. In addition, because of the difficulty in measuring absolute intensities10,11, the profiles are, almost invariably, calculated on a relative electron density scale. The lack of an absolute scale has often greatly hindered the interpretation of membrane profiles, particularly with regard to the distribution of the protein molecules9,12–16. We describe here a novel method of directly determining both the phases of the X-ray reflections and an absolute electron density scale, and how the method has been successfully tested on lecithin/cholesterol bilayers.
TL;DR: Motility and the expression of fertilizing ability by cauda epididymal rat spermatozoa were demonstrated to differ in their dependence on Ca2+ ions, indicating that sperm motility may not have to be maximized for fertilization to occur.
Abstract: SummaryMotility and the expression of fertilizing ability by cauda epididymal rat spermatozoa, incubated in a chemically defined medium, were demonstrated to differ in their dependence on Ca2+ ions. Motility was optimal at 1.7 mM Ca2+, whereas fertilization rates were significantly higher at 2.6 and 3.4 mM Ca2+. These results are interpreted as indicating that sperm motility may not have to be maximized for fertilization to occur.
TL;DR: The red cells from patients with PNH and G6PD deficiency had the shortest survival in vivo and produced the smallest amount of fragmentation and myelin forms in vitro, whereas xerocytosis with only mild to moderate hemolysis in vivo was associated with the highest amount ofMyelin forms and membrane fragments in vitro.
TL;DR: This chapter discusses chromatin structure and gene transcription in eukaryotic-genome biology, and the existence of two forms of interphase chromatin, euchromatin and heterochromatin.
Abstract: Publisher Summary This chapter discusses chromatin structure and gene transcription. A long-standing problem in the field of eukaryotic-genome biology is the question of how chromatin structure is related to transcription. The axis of modern chromosome research has had two partially overlapping phases. The first, which received particular emphasis in the 1960s, deals with the relationship of transcriptional activity to the degree of chromatin-fiber packing within the interphase nucleus. The second phase has focused on the extent to which transcriptional activity is related to local changes in the nucleoprotein structure of chromatin fibers themselves. In almost all eukaryotic cells, interphase chromatin exists as two distinct morphotypes: euchromatin and heterochromatin. Although these terms are sometimes also applied to biochemical fractions, they properly belong only in the vocabulary of cytology and, by extension, cytogenetics. The existence of two forms of interphase chromatin has been known for at least half a century.
TL;DR: This chapter describes methods for the isolation of these ribonucleoprotein (RNP) particles from eukaryotic cells and discusses some properties of heterogeneous nuclear RNA (hnRNA) particles isolated from HeLa cell nuclei.
Abstract: Publisher Summary This chapter describes methods for the isolation of these ribonucleoprotein (RNP) particles from eukaryotic cells and discusses some properties of heterogeneous nuclear RNA (hnRNA) particles isolated from HeLa cell nuclei. RNP particles containing hnRNA have been identified both cytologically and biochemically in eukaryotic cell nuclei. The method developed for isolation of HeLa hnRNP particles involves the isolation of nuclei followed by their mechanical disruption and purification of hnRNP particles by sucrose gradient centrifugation. The method of disrupting HeLa cell nuclei permits the high recovery of heterogeneous nuclear RNA in the presence of large amounts of nucleohistone. An understanding of the specificity of RNA-protein interactions in native hnRNP particles is impeded by the nucleotide sequence complexity of hnRNA and by the analytical complexity of the proteins. The specific association of protein with poly (A)-rich hnRNA sequences is demonstrated.
TL;DR: The number of concanavalin A (Con A) binding sites were determined in mouse blastocysts before and during implantation and it was found that a more than twofold increase in the Con A binding sites occurs in the mouse Blastocyst during implants.
Abstract: The number of concanavalin A (Con A) binding sites were determined in mouse blastocysts before and during implantation. In intact pregnant mice (Day 1 = day of finding vaginal plug), the Con A binding sites per blastocyst were increased from 169 million on Day 4 morning to 1160 million on Day 5 morning when implantation was under way. In pregnant mice ovariectomized on Day 3 and treated daily with 1 mg progesterone, the Con A binding sites per blastocyst on Day 9 (inactive) were 363 million; if the mice had received an additional injection of estradiol 24 hours earlier to induce implantation, the Con A binding sites were increased to 1211 millions. Thus, a more than twofold increase in the Con A binding sites occurs in the mouse blastocyst during implantation.
TL;DR: The results indicate that 4-acetoxy-A, an arOmatase inhibitor, effectively inhibits fertility by preventing estrogen production required for ovulation and implantation.
Abstract: Acetoxy-4-androstene-3,1 7-dione (4-acetoxy-A) was demonstrated to be an effective aroma- tase (estrogen synthetase) inhibitor in vitro. To study the effect of the compound on estrogen-dependent processes, rats were treated with silastic wafers containing 4-acetoxy-A (75 mg). These were inserted under the skin on Day 1 of diestrus. When housed continuously with male rats from the expected day of proestrus, 7/8 rats did not mate after 6-15 days of cohabita- tion. Other groups of rats were treated with silastic wafers containing 4-acetoxy-A (100 mg) together with s.c. injections twice daily (12.5 mg/kg). This treatment decreased the magnitude of the proestrus estrogen surge 87% as indicated by estrogen concentrations measured in ovarian vein blood. The subsequent LH surge was also inhibited over 90% as determined by measuring peripheral levels by radioimmunoassay. None of the rats mated as long as treatment lasted (4 days). When estradiol (100 �zg) was added to the wafers containing 4-acetoxy-A, the effect on mating could be reversed and mating occurred at the normal time in 9/10 rats. Treatment of mated rats with multiple injections of 4-acetoxy-A either prevented or delayed implantation. The effect was more marked at the higher dose (100 mg/kg/day). In contrast to the rat, the hamster is believed not to require estrogen for implantation. This process occurred normally in all hamsters treated with 50 mg/kg/day 4-acetoxy-A and in 73% of animals treated with 100mg/kg/day. Our results indicate that 4-acetoxy-A, an arOmatase inhibitor, effectively inhibits fertility by preventing estrogen production required for ovulation and implantation.
TL;DR: It is concluded that malnutrition during development does not exert a uniform effect on all classes of seizure phenomena.
TL;DR: The effect of certain DDT analogs on the binding of 3H-estradiol to the 8--9S estrogen binding protein of rat testicular cytosol was studied by sucrose sedimentation analysis.
TL;DR: Bilateral ablation of the middle pedal nerves suggests that the central program for pedal locomotion is distributed to each individual pedal nerve, eliminating the possibility of communication between nerves via a peripheral nerve net.
TL;DR: Rabbit antiserum to denuded eggs or isolated zona pellucida of mice is neither strain nor species specific, and fertilization in vitro was not significantly inhibited in the rat and hamster by anti-egg serum, but was inhibited in hamster eggs in cumulus.
Abstract: The effects of rabbit antisera against denuded eggs (anti-egg) and isolated zona-pellucidae (anti-zona) on fertilization were studied in different strains of mice, rats and hamsters. Treatment of denuded eggswith either anti-egg or anti-zona serum caused a more pronounced precipitate on the zona pellucida of the mouse than on that of the rat or hamster eggs. The time required to dissolve the zona pellucida by Pronase was different between the two antisera treatments and the species studied. In the mouse, in Vitro fertilization was completely inhibited by unabsorbed antizona or anti-egg serum absorbed with liver and kidney but not by anti-egg serum absorbed with ovary. Fertilization in vitro was not significantly inhibited in the rat and hamster by anti-egg serum, but was inhibited in hamster eggs in cumulus or in denuded rat and hamster eggs by anti-zonaserum. A complete inhibition of in Vivo fertilization in different strains of mice was observed after a single injection of anti-zona or anti-egg serum. A single injectionof female rats with 10-30 mg of unabsorbedanti-eggserum or 0.3 ml anti-zona serum resulted in complete to partial inhibition of fertilization, however, similar treatment failed to inhibit fertilization in hamsters. It seems that rabbit antiserum to denuded eggs or isolated zona pellucida of mice is neither strain nor species specific.
TL;DR: Results showed no group differences between protein malnourished and control animals in locomotor responsiveness to d- or l-amphetamine, recovery from behavioral asymmetry produced by a unilateral lesion of the substantia nigra, or in the development of response patterns indicative of denervation supersensitivity, suggesting that a class of brain dopamine receptors may be impaired or may have undergone homeostatic modification as a result of the undernutrition procedure.
Abstract: Four experiments were performed to evaluate the effects of developmental protein deprivation on the behavioral response of adult rats to treatments known to affect central nervous system catecholamine systems. Results showed no group differences between protein malnourished and control animals in locomotor responsiveness to d- or l-amphetamine, recovery from behavioral asymmetry produced by a unilateral lesion of the substantia nigra, or in the development of response patterns indicative of denervation supersensitivity. However, a dose-dependent diminution in the ability of apomorphine to produce stereotyped behavior was noted in the malnourished group, suggesting that a class of brain dopamine receptors may be impaired or may have undergone homeostatic modification as a result of the undernutrition procedure.
TL;DR: A suppression of testosterone, 5o-dihydrotestosterone, 5n-DHT, androstenedione and progesterone in the blood serum and a marked decrease of these steroid contents in the testicular tissue were observed.
Abstract: Cadmium chloride (CdCl2) given s.c. as a single injection of 1 mg/hamster significantly reduced the weights of the testes and epididymides 7 days after treatment. A suppression of testosterone (T), 5o-dihydrotestosterone (5n-DHT), androstenedione (�1� A) and progesterone (�4 P) in the blood serum and a marked decrease of these steroid contents in the testicular tissue were observed.