Showing papers by "Worcester Foundation for Biomedical Research published in 1969"
842 citations
TL;DR: The changes in estrogen concentration in ovarian venous plasma were similar but the major peak on the day of proestrus was sharper, being at about 1000 to 1500 hr on account of changes in blood flow.
Abstract: Estrogen levels in rat ovarian venous plasma were determined by an intravaginal bioassay. During the estrous cycle, estrogen secretion rate rose in the afternoon of diestrus (the day prior to proestrus) and continued to rise gradually throughout the night of diestrus. Maximal secretion rate was observed between 0500 and 2000 hr of proestrus: 9–11 ng estradiol equivalent (E.E.)/ovary/hr. A major fall in secretion rate was observed between 2000 and 2300 hr of proestrus. Slight rises in secretion rate were observed in the afternoons of estrus and metestrus. The changes in estrogen concentration in ovarian venous plasma were similar but the major peak on the day of proestrus was sharper, being at about 1000 to 1500 hr on account of changes in blood flow. During pregnancy, estrogen secretion rate was generally low except near term. A significant increase in estrogen secretion rate was observed in the afternoon of Day 4 (2.3 ng E.E./ovary/hr); secretion had fallen by the night of the same day. Near term, a rapi...
424 citations
TL;DR: The concentration of estradiol showed a biphasic curve throughout the menstrual cycle rising from a mean value of 2.9±0.7 during menstruation to a maximum of 31.8±2.7 around midcycle, indicating the increasing predominance of estra...
Abstract: The concentrations of unconjugated estrone and estradiol in 20 ml samples of plasma from ambulant human subjects were measured using a double-isotope derivative method (1). The concentration of estradiol (ng/100 ml plasma ±se) showed a biphasic curve throughout the menstrual cycle rising from a mean value of 2.9±0.7 during menstruation to a maximum of 31.8±2.7 around midcycle. There was a sharp fall (11.7±2.0) in the few days following ovulation, with a smaller secondary rise (19.1±2.0) in the midluteal phase. The rise in concentration of estrone was less marked than that of estradiol (4.0±0.4 during menstruation to 17.0±1.3 at midcycle). The ratio of estradiol/estrone rose significantly from 0.67±0.13 during menstruation to 1.90±0.12 around midcycle, indicating the increasing predominance of estradiol throughout the menstrual cycle. In contrast, the concentration of estrone in men (5.7±0.8), castrate (11.6±4.5) and postmenopausal women (7.1±2.7) was approximately 3-fold higher than that of estra...
176 citations
TL;DR: Small doses of prostaglandins increased steroidogenesis in the superfused adrenal glands obtained from hypophysectomized rats, mimicked in part by both adrenocorticotropin and its postulated intracellular intermediate adenosine 3', 5'-cyclic monophosphate; all three responses were inhibited by cycloheximide.
Abstract: Prostaglandins and their C20: ω 6 fatty acid precursors are present in rat adrenal glands. Small doses of prostaglandins (PGE 1 , PGE 2 , or PGF 1∞ 1.4 to 2.4 micromolar) increased steroidogenesis in the superfused adrenal glands obtained from hypophysectomized rats. This effect was mimicked in part by both adrenocorticotropin and its postulated intracellular intermediate adenosine 39, 59-cyclic monophosphate; all three responses were inhibited by cycloheximide.
134 citations
TL;DR: The procedures which may be and are being used to provide a basis for the analysis of submicrogram quantitities of prostaglandins are surveyed.
Abstract: PIP: The procedures which may be and are being used to provide a basis for the analysis of submicrogram quantitities of prostaglandins are surveyed. Discussion is focused on the following: 1) sources of standards; 2) properties (effect of different pH values, effect of blood, metabolism, solubility); 3) extraction; 4) detection; 5) estimation (ultraviolet, optical rotatory dispersion, densitometry, radioimmunoassay, enzymatic assay, isotopic methods, bioassay); 6) separation of prostaglandins (separation of PGE, PGF, and PGA with PGB compounds, separation of PGA and PGB compounds, and separation of individual prostaglandins); and 6) structural identification. Methods of prostaglandin analysis, with the required sensitivity for application to individual tissue and fluid specimens, are still in the developmental state. Although prostaglandins may be ubiquitous throughout the animal kingdom, no systematic study of their distribution has been made to date. Recent work has shown that PGE1 has a potent effect on the formation of 3',5' cyclic adenosine monophosphate (cyclic AMP) which is widely believed to be an intracellular intermediate in hormone action.
99 citations
TL;DR: It is demonstrated that mouse sperm can be capacitated in vitro to fertilize mouse eggs in the presence of bovine follicular fluid.
Abstract: SINCE the recognition of “capacitation of sperm” in the female tract1,2, fertilization in vitro of eggs has been successfully conducted by insemination of sperm recovered from the uterus for the rabbit3,4, hamster5 and mouse6. Successful fertilization of golden hamster eggs in vitro by epididymal (uncapacitated) hamster sperm5, in the presence of follicular fluid of hamster7 or cow8, or in the presence of rabbit tubal cyst fluid (our unpublished work), and that of Chinese hamster eggs in the presence of follicular fluid of golden hamster9, encouraged us to carry out the following experiment which demonstrated that mouse sperm can be capacitated in vitro to fertilize mouse eggs in the presence of bovine follicular fluid.
95 citations
TL;DR: The foregoing data, together with previous data on such other tests as the chick embryo and pertussis-treated mouse, indicate that the Limulus gel test is the most sensitive test available for the detection of endotoxin in its toxic or undegraded state.
Abstract: SummaryThe foregoing data, together with previous data on such other tests as the chick embryo and pertussis-treated mouse (7), indicate that the Limulus gel test is the most sensitive test available for the detection of endotoxin in its toxic or undegraded state. The test appears to be specific for endotoxin, since the amebocyte lysate is not clotted by normal blood or plasma or the individual vasoactive constituents known to be present in plasma of rabbits, dogs, or man. Because of its advantages in cost, simplicity, and sensitivity over all other available tests, it is to be preferred for monitoring a known endotoxemia, and for the detection of spontaneous endotoxemia.
87 citations
TL;DR: The hypothesis that p-ClPhe, a specific depletor of brain serotonin, reduces emotionality rather than increases learning ability is supported.
66 citations
TL;DR: Chromosome studies on human cells in vitro have shown that the artificial sweeteners, sodium and calcium cyclamate, can induce chromosome breaks in vitro in human cells, in both leukocyte and monolayer cultures.
Abstract: Chromosome studies on human cells in vitro have shown that the artificial sweeteners, sodium and calcium cyclamate, can induce chromosome breaks in vitro in human cells, in both leukocyte and monolayer cultures.
59 citations
TL;DR: As many as nine isoenzymes of liver alcohol dehydrogenase have been observed, and some of them seem to be hybrid forms and Steroids and ethanol may react at different subunits in the hybrid forms.
Abstract: As many as nine isoenzymes of liver alcohol dehydrogenase have been observed, and some of them seem to be hybrid forms. Steroids and ethanol may react at different subunits in the hybrid forms.
58 citations
TL;DR: It is concluded that it is unnecessary to invoke secretion of estrogen either from the ovaries or from the adrenals for induction of implantation in hamsters.
Abstract: Ten groups, five to ten animals per group were used in demonstrating that progesterone plus cortisol acetate can induce implantation and maintain embryonic growth in hamsters subjected to ovariectomy and adrenalectomy on Day 1 or on Day 4 of pregnancy, Fetal weights on Day 14 were, however, significantly lower than in sham-operated control animals, although they were not different from those in animals only ovariectomized and given progesterone. It is concluded, therefore, that it is unnecessary to invoke secretion of estrogen either from the ovaries or from the adrenals for induction of implantation in hamsters.
TL;DR: The identity of tetrahymanol and wallichiniol, isolated from Tetrahymena pyriformis and Oleandra wallichii, is established and the presence in O.wallichii of a non-oxidative squalene cyclase system similar to that operating in T. p Pyriformis is suggested.
TL;DR: Mature mice were induced to ovulate by injections of PMS and HCG and their eggs were prepared, using an air-dry technique, for the examination of chromosomes during the first and second meiotic divisions, indicating that a certain length of time may be required for capacitation of mouse sperm.
Abstract: Mature mice were induced to ovulate by injections of PMS and HCG and their eggs were prepared, using an air-dry technique, for the examination of chromosomes during the first and second meiotic divisions Sixty percent of 72 eggs recovered from follicles between 10 and 85 hours before ovulation were at prophase, whereas 91%–64% of 139 eggs were at metaphase I from 7 to 3 hours before ovulation Anaphase I and telophase I were seen in 17 eggs 45–0 hours before ovulation The bivalents were clumped together in a single mass at the earliest stage of diakinesis Separate, extended bivalents which underwent contraction up to metaphase I were observed later Counts of bivalents in 82 eggs at diakinesis and metaphase I revealed no deviation from the haploid number (n = 20) The dyads in the first polar body were usually extended and somewhat diffuse in appearance, whereas those in the egg were not A total of 295 eggs were examined from 24 females inseminated 15 hours after ovulation At 3, 35, 45 and 55 hours after ovulation 3%, 20%, 26% and 43% of recovered eggs respectively were penetrated by sperm, indicating that a certain length of time may be required for capacitation of mouse sperm Approximately 90% of eggs with an intact sperm head (Type I) were at metaphase II and nearly 100% of eggs with a swollen sperm head (Types III and IV) were at telophase II Four distinct configurations of metaphase II, “spread,” “clumped,” “compact,” and “granular” were seen in 384 unfertilized eggs recovered from 36 females at various times after induced ovulation The haploid number of dyads was observed in all of 70 eggs counted at metaphase II in the “spread” configuration The proportion of unfertilized eggs with a “compact” metaphase II increased from 2% at 5–7 hours to 12% at 24–315 hours after ovulation, while the proportion of eggs with a “granular” metaphase II increased from 11% to 47% over the same period The second meiotic metaphase exhibited these degenerative changes mainly at the end of the fertilizable period of the egg
TL;DR: As the rise in plasma activity is evident even with normal anticoagulant doses of heparin, care should be exercised in whole animal experiments when potential substrates for diamine oxidase, such as histamine and putrescine, are being studied.
TL;DR: The estrogen surge was found to occur not later than 10:00 hr on Day 4 of pseudopregnancy, rather than during the latter part of the afternoon as has been reported by other workers using biological criteria for estrogen.
Abstract: Estradiol was measured in rat ovarian venous blood plasma at different stages of pseudopregnancy by radioimmunoassay. Estradiol levels on Days 2 and 3 of pseudopregnancy were less than 50 pegs/mI plasma. On Day 4 the assay showed a mean peak value of 682 pcgs-’ml at 10:00-12:00 hr. The values then gradually declined. They were 610 pegs/mI at 14:00-16:00 hr. 467 pegs/mI at 18:00-20:00 hr, and 225 pegs/mI at 22:00-24:00 hr. At 10:00-12:00 hr on Day 5, the values were 297 pegs/mI. There was, however, no significant difference between the values at 22:00-24:00 hr on Day 4 and 10:00-12:00 hr on Day 5. The values determined at various times on Day 4 of pseudopregnancv did not show a linear regression and there was a great variation about the mean. It is therefore suggested that the ovary maintains a plateau of estrogen secretion for some hours on Day 4. This plateau of estrogen secretion probably is of importance in uterine sensitization for decidual cell reaction or implantation. In conclusion, the estrogen surge was found to occur not later than 10:00 hr on Day 4 of pseudopregnancy, rather than during the latter part of the afternoon as has been reported by other workers using biological criteria for estrogen
TL;DR: It is concluded that during pseudopregnancy or progesteronetreatment, fertilization and egg transport are disturbed and that the degeneration of fertilizedeggs occurs owing to preconditioning o...
Abstract: On various days of pseudopregnancyor of progesterone treatment, rabbits wereintravaginally inseminated and induced toovulate. Although fertilization was not completelyinhibited in all animals during activepseudopregnancy or continuous progesteronetreatment, total degeneration of eggs occurredby day 6. In general, the proportion of sterileanimals, the percentage of total eggs fertilized,the rate of egg transport from the tube to theuterus and the induction of egg degenerationwere quite similar in both pseudopregnant andprogesterone-treated animals. When eggs frompseudopregnant or progesterone-treated rabbitswere transferred to untreated rabbits, implantationoccurred. When eggs from untreated rabbitswere transferred to the pseudopregnant or progesterone-treated rabbits, degeneration occurredin both the tube and uterus. It is concludedthat during pseudopregnancy or progesteronetreatment, fertilization and egg transport aredisturbed and that the degeneration of fertilizedeggs occurs owing to preconditioning o...
TL;DR: It was concluded that the C-26 oxygenation of cholesterol during its biosynthetic conversion to tigogenin in D. samen, does not require the intermediacy of a C-24 (or C-25) double bond.
TL;DR: Biological studies on the synthetic prostaglandins, and certain unnatural synthetic stereoisomers, have been undertaken first to provide biological confirmation of the chemical synthesis and, second, to explore the metabolism and pharmacological activity of various stereoisomer in areas where the prostaglandsins may be of clinical use.
Abstract: THE total synthesis of prostaglandin E1 and prostaglandin F1a has recently been achieved by methods which also make available various derivatives and steroisomers of the prostaglandin series1,2 Biological studies on the synthetic prostaglandins, and certain unnatural synthetic stereoisomers, have been undertaken first to provide biological confirmation of the chemical synthesis and, second, to explore the metabolism and pharmacological activity of various stereoisomers in areas where the prostaglandins may be of clinical use These include the regulation of gastric secretion3,4, blood platelet aggregation5, blood pressure, lipolysis, carbohydrate metabolism6 and corticosteroidogenesis7
TL;DR: Several pathways leading from cholesterol to pregnenolone are established, including an enzymatic, concerted attack of oxygen on cholesterol to form 20α, 22R-dihydroxycholesterol which then is oxidatively cleaved to pregnanolone.
TL;DR: In this paper, the urinary metabolites of 17α-ethynylestradiol and 3-methyl ether (mestranol) from New Zealand rabbits were identified as urinary metabolites.
TL;DR: Administration of DHA (2.5, 5 or 10 mg/day sc) on days 2–5 interfered with pregnancy in rats and could be produced in intact and adrenalectomized rats and was potentiated in partially hepatectomized ones, total failure of implantation being produced by daily doses of 10, 10 and 5 mg, respectively.
Abstract: Administration of DHA (2.5, 5 or 10 mg/day sc) on days 2–5 interfered with pregnancy in rats. This effect could be produced in intact and adrenalectomized rats and was potentiated in partially hepatectomized ones, total failure of implantation being produced by daily doses of 10, 10 and 5 mg, respectively. Although doses of 2.5–10 mg/day of DHA greatly reduced the deciduomal response of the uterus to trauma in pseudopregnant rats, implantation failure was due not to this, but to expulsion of the eggs from the reproductive tract by day 5 of pregnancy. This effect was similar to that produced by administration of estrogens. Cortisol acetate did not influence the effect of DHA on pregnancy. In intact or adrenalectomized immature rats, the uterus responded to administration of DHA with a dose dependent increase in weight and histological changes similar to those produced by estradiol. In ovariectomized and ovariectomized-adrenalectomized animals smaller responses to similar doses of DHA were produced. In inta...
TL;DR: The results obtained indicate that the prolactin effects on ovarian steroidogenesis may be mediated, at least in part, by changes in cholesterol storage and perhaps discharge in the mouse testis.
Abstract: A SERIES of experiments concerned with the influence of prolactin on spermatogenesis and on the accessory reproductive structures in mice led to the suggestion that prolactin can stimulate the production of testicular androgens1. In the female, prolactin is known to affect the synthesis of ovarian steroid hormones; its luteotropic action in the mouse and the rat is particularly well established. The results obtained in the rat2,3, the rabbit4 and in the perfused bovine ovary5 indicate that the prolactin effects on ovarian steroidogenesis may be mediated, at least in part, by changes in cholesterol storage and perhaps discharge. The present work investigates the influence of prolactin on cholesterol stores in the mouse testis.
TL;DR: An androstane derivative covalently bound to agarose was effective in removing testosterone binding globulin from plasma and the protein could subsequently be separated from the reagent in low yield by means of guanidine.
TL;DR: It was considered that the increased neutral fraction and decreased acid fraction was due to inhibition of aldehyde dehydrogenase and activation of alcohol dehydrogen enzyme by virtue of an ethanol-induced increase in brain NADPH/NADP ratio.
TL;DR: It is shown that during the transformation from lanosterol to cholesterol the 2-pro-R hydrogen of mevalonic acid at C-1 retains its β configuration, and atC-7 is inverted from the α to the β orientation, and in addition to the three labels located at carbon atoms 1, 7, and 15, the presence of two further tritium atoms was indicated.
TL;DR: It appears that colchicine interferes with sperm penetration, the second meiotic division and normal cleavage in the mouse, but no effect was observed in the rabbit with similar dose levels.
Abstract: Female mice were injected with various doses of colchicine before or after induced ovulation and artificially inseminated. Their eggs were recovered and prepared according to an air-dry method for the examination of chromosomes. In the unpenetrated eggs examined four and one-half to six and one-half hours after ovulation, the chromosomes were scattered throughout the ooplasm in the colchicine treated mice.
When examined four and one-half to six and one-half hours after ovulation, only 7% of 353 eggs recovered from females injected with 0.5, 1.5 or 3.0 μg of colchicine/gm body weight earlier than three and one-half hours after ovulation were penetrated, but 35% of 144 eggs from untreated females and 41% of 73 eggs from females given colchicine at three and one-half hours after ovulation were penetrated. When examined 23 to 25 hours after ovulation 32% of 76 eggs from females treated before ovulation, 87% of 93 eggs from females treated at three and one-half hours after ovulation, and 94% of 78 eggs from control females were penetrated.
In 84% of 44 penetrated eggs from treated females their chromosomes were still at metaphase II while the sperm head had begun its transformation. By contrast, of 42 control eggs containing transforming sperm heads, 98% displayed anaphase or telophase of the second meiotic division.
Chromosome counts of eggs at the first cleavage revealed heteroploidy ranging from the hypohaploid to the triploid condition and the absence of normal diploid eggs from treated females whereas the majority of eggs from control females displayed the diploid number of chromosomes (2n = 40).
Four groups of rabbit eggs were recovered from does injected with colchicine before or after ovulation. Chromosome scattering and inhibition of fertilization were not observed. It appears that colchicine interferes with sperm penetration, the second meiotic division and normal cleavage in the mouse, but no effect was observed in the rabbit with similar dose levels.
TL;DR: No fetal development was observed when six-day eggs were transferred to estrous ferrets treated with various progestins, but a few implantations occurred.
Abstract: Ferret eggs recovered from oviducts and uteri at various times after insemination were transferred to the uteri of recipient animals on various days of pseudopregnancy. Fifteen per cent of newly fertilized two day eggs recovered from oviducts were implanted when transferred to uteri of two-day pseudopregnant ferrets but only 5% developed to fetuses. Synchronous transfer of four-, six-, seven- and eight-day eggs to uteri of four-, six-, seven- and eight-day pseudopregnant ferrets resulted in 44-62% of implantations, but only 21–41% of eggs developed to fetuses. Twenty-one-fifty-seven percent of eggs were implanted, and 8–29% of eggs developed to fetuses when eggs were transferred to uteri of ferrets that had ovulated two days later. When transferred to uteri of ferrets that had ovulated two days earlier none developed to fetuses although 33–50% of transferred eggs implanted. No fetal development was observed when six-day eggs were transferred to estrous ferrets treated with various progestins, but a few implantations (3–17%) occurred.
TL;DR: There were no significant differences in formation of radioactive cor-ticosterone between control, hypophysectomized and ACTH-treated groups, suggesting that cor-ticsosterone is formed rapidly from circulating cholesterol and secreted instantaneously and that this conversion is maintained to some extent in the absence of ACTH.
Abstract: The effect of ACTH on cortico-steroid biogenesis from cholesterol by rat adrenal glands in vivo has been studied. 1. Rapid synthesis and secretion of radioactive corticosterone by the rat adrenal was observed after “retrograde” infusion of cholesterol-7α-3H through the adrenal vein. There were no significant differences in formation of radioactive cor-ticosterone between control, hypophysectomized and ACTH-treated groups, suggesting that cor-ticosterone is formed rapidly from circulating cholesterol and secreted instantaneously and that this conversion is maintained to some extent in the absence of ACTH. 2. The effect of ACTH on radioactive cortico-sterone production by adrenals of rats in which the adrenal cholesterol had been labeled by intravenous administration of cholesterol-7α-3H 24 hr earlier has been observed. The specific activities of corticosterone from control and ACTH-treated groups were lower than those from adrenals of hypophysectomized animals. These results support the suggestion that the...
TL;DR: In this paper, the excretion of radioactivity via the urine vas greater than that observed earlier for the related cyclopentyl ether (Quinestrol) was observed.