Showing papers by "Worcester Foundation for Biomedical Research published in 1973"
TL;DR: Large and irregular changes in plasma levels of T are unlike the fairly stable levels observed in the human but bear certain resemblance to the pulsatile release of T described in bulls and rams and perhaps also to the social dominance related differences in plasma T levels in Rhesus monkeys.
Abstract: Testosterone (T) levels in the plasma of male laboratory rats and mice were measured by radioimmunoassay. There was a striking individual variation with values ranging from less than 1 ng/ml to over 30 ng/ml in mice of the same age and strain housed under identical conditions. Using chronic indwelling catheters inserted into a jugular vein, blood was collected from adult conscious male rats every 24 hr for 4 or 8 days and every 30 min for 2l/2 or 8 hr. Considerable differences in plasma T levels were observed between different animals, and 2– to 5–fold fluctuations of T concentrations in the plasma were detected between samples collected from the same animal at different times. These large and irregular changes in plasma levels of T are unlike the fairly stable levels observed in the human but bear certain resemblance to the pulsatile release of T described in bulls and rams and perhaps also to the social dominance related differences in plasma T levels in Rhesus monkeys. (Endocrinology 92: 1223, 1973)
325 citations
TL;DR: Structural features of over 100 steroids and some non—steroids were evaluated systematically as inhibitors of estrogen biosynthesis in human placental microsomes and the 17–keto was superior to the 17P—hydroxy group in providing inhibitory properties in all cases.
Abstract: Structural features of over 100 steroids and some non—steroids were evaluated systematically as inhibitors of estrogen biosynthesis in human placental microsomes. The microsomes were preincubated with and without potential inhibitors, and then were incubated with [4–14C] androst–4–ene–3,17–dione or [4–14C]3P—hydroxyandrost— S—en—17–one (DHA) and an NADPH generating system. After adding tritiated estrogens as recovery markers, the estrogens were isolated by thin—layer chromatography and were assayed using dual—label scintillation counting to determine percent conversion and inhibition produced. C10 A4–3–keto compounds were better inhibitors than the corresponding ring A reduced (5
294 citations
TL;DR: Serum testosterone concentration was decreased in many of these subjects without consistent abnormalities in the other hormones, suggesting that decreased sexual function in male addicts may be partially due to a decrease in serum testosterone concentration.
128 citations
TL;DR: Values obtained for E2 in aliquots from a single pool of serum measured by RIA, by protein binding using uterine cytosol and by double isotope derivative methods were 3000 pg/ml, 170 pg/ML, and 82 pg/ ml, respectively, indicating that the bulk of the displacement in the RIA was due to substances other than Eo (spurious E2).
Abstract: Using radioimmunoassay (RIA) to determine the levels of estradiol (E2) and estrone (E1) in sera from immature female rats between 1–24 days of age, extremely high values were obtained. Maximum levels for E2 were found at 10 and 18 days and for E1 at 10 days. (E2 day 10, mean = 2235 pg/ml, range 924-5500; day 18, mean = 1691 pg/ml, range = 282–1898. E1: day 10, mean = 1060 pg/ml, range = 282–1898 pg/ ml.) An injection of 100 Hg testosterone propionate (TP) at 5 days of age suppressed the peaks of E2 and E1(Values obtained for E2 in aliquots from a single pool of serum measured by RIA, by protein binding using uterine cytosol and by double isotope derivative methods were 3000 pg/ml, 170 pg/ml, and 82 pg/ml, respectively, indicating that the bulk of the displacement in the RIA was due to substances other than Eo (spurious E2). In contrast the values obtained by the 3 assay techniques for E, were similar (940 pg/ml, 1045 pg/ml, and 780 pg/ml, respectively). To determine the source of the spurious E2 and of th...
118 citations
TL;DR: The relative ability to respond to exogenous gonadotropins appears to be preserved despite ageing and loss of libido and potentia, and the absolute response is somewhat less in old men as compared to young.
103 citations
TL;DR: Results in the present study clearly indicate that subcutaneous injections of indomethacin to the pregnant mice on days 1,2,3 and 4 of pregnancy terminate pregnancy in 100 percent of the animals.
101 citations
TL;DR: It is suggested that hydrolysis of cholesterol esters present in the testis is required for normal production of androgenic steroids.
83 citations
TL;DR: Olivetol, which represents a partial structure for all of the compounds tested, showed high activity, indicating that the inhibitory power of the cannabinoids resides in the aromatic portion of the molecule.
80 citations
73 citations
TL;DR: It is concluded that more eggs are penetrated in a short period of time followed late transfers because there is tile ilnmediate posSii)ility of egg and sperm Ineeting.
Abstract: Unfertilized eggs recovered fronu donor ral)bits shortly after ovulation induced by injection of HCG were transferred to the oviducts of mated recipients or recipients inseminated with 200 nuillion spermatozoa and injected with HCG at known times. It was found that although only 407r of such eggs were penetrated in 1.5 h following transfer to mated recipients at 9-9.75 h after mating, 58 and 66� were penetrated during the same period if transfers were delayed until 13.75-14.25 and 19.5-20.0 h after mating, respectively. By 24 h after nuating the percentage of eggs penetrated had fallen again to 43%. It was shown by ligation of the oviduct at the uterotubal junction that adequate sperm were in the oviduct by 9.25-9.75 h after inselllinatiOn to ensure this enhanced fertilization following transfer at 14 or 17 h hut not 20 lu after insemination. Tiuese results implied that although spernu continued to migrate from the utenis into the oviduct, more sperm in the oviduct at later times was not responsible for this plsenomellon. Further experiments in which ligation was done at the anipullar-isthmic junction or the middle of the isthnuls showed that sperm were retaiiued in the proxilnal isthmus just above the uterotuhal junction for several hours. When whole ovidncts were fixed and serially sectioned and the number .‘.nd distribution of sperm determined, it waS fnund that at 9 h after insemination few sperm were at the site of fertilization. In the oviducts of animals killed at 14 or 20 h after insemination, the spernu in tlue oviduct (irrespective of whether tile uterotubal junction luad been ligated or not) had become redistributed with many more found at the site of fertilization. It is concluded that more eggs are penetrated in a short period of time (1.5 h) followed late transfers because there is tile ilnmediate posSii)ility of egg and sperm Ineeting.
62 citations
TL;DR: Prostaglandins PGE 2 and PGF 2α depressed significantly the plasma testosterone levels when given subcutaneously to mature male rats at a dose of 500 μgm/rat/injection, b.i.d.
TL;DR: The data supports the suggestion of others that Ca2+ may be crucially involved in the transmission of the signal arising from ACTH-receptor interaction to the adenyl cyclase, and indicates that in the action of ACTH the Ca2- requirement is greater for the events before the formation of cyclic AMP.
TL;DR: It is demonstrated that rat sperm do need capacitation in the female tract before they are capable of penetrating the egg and that eggs obtained from superovulated mature and immature females were as fertilizable in vitro as were those recovered from the naturally ovulated females.
Abstract: Rat eggs were recovered from oviducts and inseminated with sperm collected from either the uterus of mated females or the cauda epididymis of males. A mixture of a modified Krebs-Ringer bicarbonate solution and rat serum (4:1) was usually used to incubate the sperm and eggs for 8-12 h. The presence of bovine serum albumin and rat serum in the medium appeared to be very important for the fertilization of rat eggs in vitro. When eggs recovered 1-5 h after ovulation were inseminated with sperm recovered from the uterus of females mated 0.5-1, 4-5, and 10-11 h previously, the proportions of eggs penetrated were 4-7, 85-95, and 32-55%, respectively. Eggs obtained from superovulated mature and immature females were as fertilizable in vitro as were those recovered from the naturally ovulated females. Sperm penetration, however, was not observed when preincubated epididymal sperm were used under the present experimental conditions. This fact and the significantly higher proportions of eggs penetrated by sperm recovered from the uterus at 4-5 and 10-11 h than at 0.5.-i h after mating demonstrated that rat sperm do need capacitation in the female tract before they are capable of penetrating the egg. The time required for capacitation of rat sperm in the female tract appeared to be about 4-5 h. Polyspermy and the presence of supplementary sperm in both the fertilized and unfertilized eggs were very frequently observed.
TL;DR: It is suggested that in human subjects the rise of fetal cortisol is a result of the stress of labor.
TL;DR: The data appear to indicate that activation of the ventral pathway induces electrocortical arousal, while depletion of amines within this pathway may induce somnolence.
TL;DR: The interfollicular tissue of animals treated with testosterone propionate accumulated very little lipid between postnatal days 5 and 7 and exhibited very little 3β-hydroxysteroid dehydrogenase activity.
Abstract: The development of the interstitial tissue and of the steroidogenic capability of the infantile rat ovary were examined by light microscopy, by histochemistry and by in vitro incubation. Ovaries from 5, 7, 10, 12 and 14-day-old normal rats and from rats that had received 100μg testosterone propionate or sesame oil at 5 days of age were utilized. The structural development of the infantile rat ovary was examined in 0.5 μ sections of Epon-embedded tissues which had been fixed with glutaraldehyde and osmium. The lipid content of interstitial tissue in untreated animals was minimal at 5 days of age and then increased. The greatest change occurred between postnatal days 5 and 7. 3β-Hydroxysteroid dehydrogenase activity also became prominent at this time. The interfollicular tissue of animals treated with testosterone propionate accumulated very little lipid between postnatal days 5 and 7 and exhibited very little 3β-hydroxysteroid dehydrogenase activity. Fibroblasts rather than interstitial cells were the pred...
TL;DR: F fertilization of intact rat eggs in vitro and the results obtained are reported.
Abstract: AFTER the recognition of “capacitation of sperm” by Austin1 and Chang2, successful in vitro fertilization of mammalian eggs was achieved in many species3–17. Although fertilization of rat eggs in vitro has been attempted1,18–20, incorporation of sperm into the vitellus was observed only after the dissolution of zona pellucida by chymotrypsin19. Here we report fertilization of intact rat eggs in vitro and the results obtained.
TL;DR: The results clearly support the thesis that intravascular detoxification plays a dominant role in the increased resistance of tolerant animals to endotoxin.
Abstract: We designed this study to determine the contribution to host defense of the humoral detoxifying mechanism in endotoxin-tolerant animals. Compared with normal serum, sera from tolerant rabbits proved to be a much more potent medium for the detoxification of endotoxins. A fivefold increase in the activity of heatstable, organophosphate-resistant esterase in tolerant serum was shown to be associated with the low-density lipoprotein fraction. The response of tolerant rabbits to challenge with endotoxin was immediate and was manifested by a sharp drop in ionized calcium in serum and a rapid formation of endotoxin-lipoprotein (esterase) complexes in the circulation. Tolerant rabbits were capable of effecting a rapid intravascular detoxification of endotoxin in spite of total occlusion of blood flow to the liver and spleen. These results clearly support the thesis that intravascular detoxification plays a dominant role in the increased resistance of tolerant animals to endotoxin.
TL;DR: The effects of methamphetamine and chlordiazepoxide were studied in a situation in which the same motor response, licking a water-filled tube, served as a schedule-controlled and as an adjunctive behavior.
Abstract: The effects of methamphetamine (0.03–1.7 mg/kg) and chlordiazepoxide (3.0–30.0 mg/kg) were studied in a situation in which the same motor response, licking a water-filled tube, served as a schedule-controlled and as an adjunctive behavior. Rats responded under a 3-min fixed-interval (FI) schedule of food presentation in which the required response was a lick on the tube (schedule-controlled); licking also occurred following every food presentation (adjunctive). Adjunctive licking occurred at a high, steady rate, but schedule-controlled licking was emitted at a changing rate over time, characteristic of FI schedules. Both drugs had little effect on overall adjunctive licking, except for decreases at the highest doses, but there were changes in the pattern of adjunctive licking. Methamphetamine produced only decreases in schedule-controlled licking, but chlordiazepoxide produced dose-dependent increases. In general, the magnitude of drug effect on local rates of responding within the FI was related to control rates of responding within the same periods, but there were instances in which the magnitude of effect depended also on whether licking was adjunctive or schedule-controlled.
TL;DR: The fertilization of hamster eggs in vivo by uterine insemination of epididymal spermatozoa treated with natural trypsin inhibitors or synthetic protease inhibitors and embryonic development following such treatment of spermatozosa are described.
Abstract: The fertilization of hamster eggs in vivo by uterine insemination of epididymal spermatozoa treated with natural trypsin inhibitors or synthetic protease inhibitors and embryonic development following such treatment of spermatozoa are described. Fertilizing capacity of hamster epididymal spermatozoa was inhibited by treatment with synthetic protease inhibitors such as N-alpha-rho-tosyl-L-lysin chloromethyl ketone hydrochloric acid or L-1-tosylamide-2-phenyl-ethyl-chloromethyl ketone but not by the natural trypsin inhibitors such as soybean or ovomucoid trypsin inhibitors. The number of living fetuses was significantly (p<.05) reduced by treatment of spermatozoa with .003-.005% synthetic protease inhibitors but the appearance and the weight of fetuses were not affected.(AUTHORS MODIFIED)
TL;DR: Es konnte gezeigt werden, dass die 2 schnell sedimentierende Komponenten, isoliert aus Kaninchensamenflüssigkeit von verschiedenen Zonen eines unterbrochenen Sucrosegradienten in elektronenmikroskopischen Aufnahmen vesikuläre Strukturen darstellen.
Abstract: Es konnte gezeigt werden, dass die 2 schnell sedimentierende Komponenten, isoliert aus Kaninchensamenflussigkeit von verschiedenen Zonen eines unterbrochenen Sucrosegradienten in elektronenmikroskopischen Aufnahmen vesikulare Strukturen darstellen. Die langsamer sedimentierende Komponente (85S) hat einen kleineren Durchmesser (507 A) und ist weniger dicht (1.16 g/cm3) als die schneller sedimentierende Komponente mit einem durchschnittlichen Durchmesser von 609 A und einer Dichte von 1.20 g/cm3. Die Dekapazitationsaktivitat in Samenflussigkeit kommt beiden zu und nicht nur wie bis jetzt angenommen wurde, der 85S Komponente. Zwei verschiedene Vesikeltypen wurden auch in der Samenflussigkeit von Mensch und Stier gefunden.
TL;DR: It is concluded that for the production of PGF 2α both estrogen and progesterone are necessary and that the pretreatment with progester one followed by estrogen results in the maximum production ofPGF 2 α.
TL;DR: The correspondance between the regional levels of brain biogenic amines and the occurrence of the sleep states is poor since REM and slow-wave were normal on the third day after reserpine, i.p., while norepinephrine and serotonin levels were depressed by about 50% at that time.
Abstract: Cats receiving 0.15 mg/kg of reserpine, i.p., had rapid eye movement (REM) sleep suppressed for two days and showed increased ponto-geniculo-occipital (PGO) spikes in waking and slow-wave sleep; these effects were not reversed by administration of dopa. Reserpine (0.125 mg) given intraventricularly, however, significantly increased REM sleep and did not change the frequency of PGO spikes in waking and slow-wave sleep. The differences in sleep characteristics seen between i.p. and central administration of reserpine are probably due to (a) the marked peripheral autonomic side effects accompanying reserpine, i.p., and (b) the much smaller central depletion of brain monoamines following intraventricular reserpine. Also, the correspondance between the regional levels of brain biogenic amines and the occurrence of the sleep states is poor since REM and slow-wave were normal on the third day after reserpine, i.p., while norepinephrine and serotonin levels were depressed by about 50% at that time.
TL;DR: The effect of prostaglandins E1, E2 and F2α on sperm transport and fertilization were studied in the rabbit and there was a significant difference in fertilization rates in control animals.
TL;DR: In contrast to findings reported with other species, inhibition of glycolysis with 2-deoxy-D-glucose does not increase feeding in cats, but produces dose-dependent decreases in food intake, suggesting glucostatic control of feeding may be qualitatively different in cats than in other species.
TL;DR: A detailed evaluation of the results obtained by the numerous investigators gave us no definitive clue as to the nature of the discrepancies and decided to run similar studies with greater emphasis on placebo and time controls with respect to steady-state concentrations and rates of synthesis of serotonin and 5-HIAA.
Abstract: Serotonin levels in rabbit brain were reported to be decreased by single doses of ethanol in viv0.'~~~~~25 Subsequently, several groups were unable to confirm this finding in rabbit brain12J3.21,29 or in rat brain.8,9.31,33 Other groups reported an increase in rat brain serotonin levels under the influence of ethanol and other anesthetic~.2,3,~6,~~ Recent studies of the effect of single doses of ethanol on serotonin steady-state concentrations and rates of biosynthesis as determined by the MAO-inhibitorinduced increase in serotonin are just as contradictory. Tyce and colleague^^^-^^ first reported that the concentration and turnover of serotonin in brain was normal in ethanol-intoxicated rats; but, later, Tyce and associates38 qualified the statement to indicate that although the steady-state concentration was not altered, the rate of serotonin accumulation after pargyline was decreased by ethanol. Palaic and colleaguesz7 reported that the levels of serotonin in rat brain were markedly increased at one hour and six hours after ethanol administration and still elevated at 24 hours after the single dose and that the rate of serotonin accumulation after pargyline was increased by ethanol. Reichle and c o w ~ r k e r s ~ ~ also reported that acute amounts of ethanol increased brain serotonin levels. Kuriyama and associatesz3 found no difference in brain serotonin levels in mice after ethanol and a slight but not significant decrease in the pargyline induced serotonin accumulation. They also reported that single doses of ethanol had no significant effect on mouse brain tryptophan-5hydroxylase consistent with the observation that ethanol had no effect on serotonin synthesis. Tyce and colleagues38 reported that ethanol did not alter the brain concentration of 5-HIAA and slightly but significantly blocked the pargylineinduced decrease in 5-HIAA. Palaic and associates27 reported that ethanol induced a decrease in the brain 5-HIAA levels and an acceleration of the pargylineinduced decrease in 5-HIAA. A detailed evaluation of the results obtained by the numerous investigators gave us no definitive clue as to the nature of the discrepancies. We therefore decided to run similar studies with greater emphasis on placebo and time controls with respect to steady-state concentrations and rates of synthesis of serotonin and 5-HIAA.
TL;DR: Results suggest substantial turnover of DNA and RNA at the non-permissive temperature, and might explain the apparent low incidence of mutants recovered in studies thus far.
TL;DR: Fenfluramine produced a dose-dependent, biphasic effect on sleep-waking patterns in cats and Serotonin was significantly reduced in the neocortex, pyriform lobe, cerebellum and hindbrain at the time of the drug's peak effect on SWS suggesting that the fen fluramine-induced increase in SWS is mediated via serotonin dependent mechanisms.
Abstract: Fenfluramine produced a dose-dependent, biphasic effect on sleep-waking patterns in cats. At low doses (0.4 mg/kg) fenfluramine elicited an increase in total waking time and a marked reduction in REM sleep, similar to that seen after administration of amphetamine, without affecting SWS. At anorectic doses (5.0 mg/kg) fenfluramine almost completely suppressed REM sleep, reduced waking time and increased SWS, an effect similar to that seen after administration of 5-HTP, the precursor of serotonin. The fenfluramine-induced increase in SWS was facilitated by 5-HTP and blocked by LSD, a serotonin antagonist. Serotonin was significantly reduced in the neocortex, pyriform lobe, cerebellum and hindbrain at the time of the drug's peak effect on SWS suggesting that the fenfluramine-induced increase in SWS is mediated via serotonin dependent mechanisms.
TL;DR: From this study it appears that the hamster ovary unlike that of the rat secretes appreciable quantities of estrogens during pregnancy and PSP, which may explain why hamsters are much more susceptible to luteolytic agents compared to rats and resistant to antifertility effects of estrogen.
TL;DR: Antibodies to the F metabolite 9α, 11α-dihydro-15-keto-prostanoic acid, produced in the rabbit, do not cross react with any of the primary PGs, and preliminary data are presented on levels of these F metabolites (I and III).