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Showing papers by "Worcester Foundation for Biomedical Research published in 1966"


Journal ArticleDOI
TL;DR: The capacity of the tissue to convert progesterone to androgens increased sharply at 15½ days, that is, at about the time of differentiation of the accessory reproductive system, and was maximal at 18½ days and was maintained at this level through the first postnatal day.
Abstract: Testes from rat embryos of 13½-21½ days of age were incubated with 7-3H-progesterone. The radioactive testosterone and androstenedione produced were estimated using the double isotope dilution method. The capacity of the tissue to convert progesterone to androgens increased sharply at 15½ days, that is, at about the time of differentiation of the accessory reproductive system. Conversion was maximal at 18½ days and was maintained at this level through the first postnatal day. The effects of tissue:substrate ratio, TPN and duration of incubation as well as of intrauterine decapitation of the fetus on the production of androgens were also studied. The relationship of the findings to sexual differentiation is discussed. (Endocrinology 78: 245, 1966)

97 citations



Journal ArticleDOI
TL;DR: In the granulosa cells in some of the graafian follicles, 3β-OHD activity became demonstrable and G6PD activity increased markedly on the second day of the estrous cycle, indicating a change in the distribution and intensity of the activities of these enzymes.
Abstract: Ovaries of 120- to 140-day-old rats were examined histochemically throughout the estrous cycle for changes in distribution and intensity of the activities of 3 carbohydratemetabolizing and 2 steroid-converting enzymes. The enzymes of carbohydrate oxidation were: lactic dehydrogenase (LD), succinic dehydrogenase (SD), and glucose-6-phosphate dehydrogenase (G6PD). 20α-Hydroxypregn-4-en-3-one and dehydroepiandrosterone were used as substrates for the study of 20α-hydroxysteroid dehydrogenase (20α-OHD) and Δ6-3β-hydroxysteroid dehydrogenase (3β-OHD) activities, respectively. Infoldings of the germinal epithelium were distinguished from the rest of the surface epithelium by a stronger activity of certain carbohydrate-metabolizing enzymes. Primary follicles, closely associated with these epithelial infoldings, exhibited identical histochemical characteristics. In the granulosa cells in some of the graafian follicles, 3β-OHD activity became demonstrable and G6PD activity increased markedly on the second day of d...

96 citations


Journal ArticleDOI
TL;DR: Fifty-four rabbits in groups of 6 were subcutaneously injected with progesterone or fed medroxyprogesterone acetate (MPA) for 3 days either before or after artificial insemination and an ovulation-inducing injection of HCG to observe degeneration of eggs.
Abstract: Fifty-four rabbits in groups of 6 were subcutaneously injected with progesterone or fed medroxyprogesterone acetate (MPA) for 3 days either before or after artificial insemination and an ovulation-inducing injection of HCG. Feeding with progesterone (2 mg/rabbit/day) before or after ovulation, or by injection after ovulation, had no effect on the development of eggs when examined on day 6. Subcutaneous injection of progesterone or feeding with MPA at the same dose before ovulation, however, induced a complete degeneration of eggs. Oral administration of MPA before ovulation at doses less than 2 mg/rabbit/day for 3 days was progressively less effective. Fifty-six rabbits were fed ethinyl estradiol (EE) or MPA on various days before and/or after insemination, or with one compound before and the other after insemination. When examined on day 6, degeneration of eggs was observed whenever 0.05 mg/rabbit/day of EE was fed for 3 days after ovulation or MPA (2 mg/rabbit/day) for 3 days before ovulation. Although ...

67 citations


Journal ArticleDOI
TL;DR: In this article, the effect of the biological substrates succinate, malate, glutamate, citrate, isocitrate, α-ketoglutarate, β-hydroxybutyrate on 11β-hydroxylation of DOC in rat adrenal mitochondria has been studied.

66 citations



Journal ArticleDOI
TL;DR: The plasma testosterone response to administration of ACTH in patients was extremely variable, increasing in some and decreasing in others, and the response of urinary 17-KS to hormone administration was often of diagnostic value and...
Abstract: Plasma testosterone and urinary 17-ketosteroids were measured in women with idiopathic hirsutism (IH) or polycystic ovaries (PCO). Base line plasma testosterone values were elevated more often than were urinary 17-ketosteroids (17-KS). In an attempt to define the sources of androgen, the patients, and a group of normal volunteers, were treated with ACTH, dexamethasone and with dexamethasone plus HCG. Plasma testosterone in normal women showed little if any change during treatment with these hormones. The plasma testosterone response to administration of ACTH in patients was extremely variable, increasing in some and decreasing in others. IH patients usually had a decrease in testosterone levels while they received dexamethasone; those with PCO had less consistent changes. Stimulation with HCG caused appreciable increases in testosterone in all groups. Plasma testosterone fell after ovarian wedge resection in 4 women. The response of urinary 17-KS to hormone administration was often of diagnostic value and...

65 citations



Journal ArticleDOI
TL;DR: Dimethyl sulfone, however, is not reduced to either the sulfoxide or the sulfide but is excreted unchanged, and is also found in the urine of untreated rabbits.

59 citations


Journal ArticleDOI
TL;DR: EE was found to be the most effective estrogen in preventing normal blastocyst development in mature female rabbits and was used in the remainder of the study.
Abstract: A total of 251 mature female rabbits was used in this study. One hundred eight of these were divided into groups of 6 and orally dosed at 24, 48 and 72 hr after insemination and injection of human chorionic gonadotrophin (HCG), with graded doses of various estrogens [stilbestrol, estradiol cyclopentylpropionate (ECP), estrone, estradiol and ethinyl estradiol (EE) ], dissolved in 1 ml cottonseed oil. The eggs were recovered on day 6, and classified according to their development. EE was found to be the most effective estrogen in preventing normal blastocyst development. The ED50 (and its 95 % probability limits) was 0.012 (0.010–0.014) mg/ rabbit/day. EE was therefore used in the remainder of the study. Eighteen rabbits were given a single dose of 0.05 mg EE at 24, 48 or 72 hr after insemination and injection of HCG and no significant difference in the percentage of blastocyst development was found. This dose given at 24 hr was found to be as effective as a total dose of 0.048 mg EE given over 3 days in re...

58 citations


Journal ArticleDOI
01 Jun 1966-Steroids
TL;DR: A large quantitative peak of total estrogen excretion during the three days immediately preceding ovulation and a secon smaller peak occured 6–10 days following ovulation were observed.

Journal ArticleDOI
TL;DR: It has been calculated that, since no more than one third of testosterone in female plasma can arise from direct secretion, the ratio of androstenedione to testosterone in ovarian venous plasma should be about 20:1.
Abstract: Recent evidence has been presented that a major fraction of plasma testosterone in the adult female is derived from peripheral conversion of plasma androstenedione. This conclusion is based upon the demonstration of a considerable conversion ratio (15%) from infused 3H-androstenedione to its conversion product testosterone and the finding of relatively large amounts (0.140 μg/100 ml) of androstenedione in female plasma (1). The back conversion of both dehydroisoandrosterone and testosterone to plasma androstenedione is minimal (2), suggesting that androstenedione must be a major secretory product of the ovary and/or adrenal cortex. It has been calculated that, since no more than one third of testosterone in female plasma can arise from direct secretion, the ratio of androstenedione to testosterone in ovarian venous plasma should be about 20:1 (1).

Journal ArticleDOI
TL;DR: It is suggested that theophylline action in rat adrenals has two antagonistic components, potentiation of the steroidogenic action by protection of .3′,5′-AMP, and reduction of theabolic action by inhibition of protein synthesis.
Abstract: SummaryThe action of several peptide and amine hormones on their target tissues involves the generation of adenosine-3′-5′-monophosphate (3′5′-AMP). Inhibition of the enzymatic breakdown of 3′5′-AMP by high concentrations of theophylline results, in most of these hormone-tissue systems, in a simulation of the hormone effect or in a po-tentiation of its action. Adrenocorticotrophin (ACTH) action on steroidogenesis in adrenals, which involves 3′,5′-AMP formation; is not affected by theophylline to the same degree as the actions of other hormones on their target tissues. A possible explanation for this discrepancy may be found in the fact that high concentrations of theophylline inhibit protein synthesis in surviving rat adrenal tissue, a process which is known to be involved in the steroidogenic action of both ACTH and 3′,5′-AMP. It is suggested that theophylline action in rat adrenals has two antagonistic components, (1) potentiation of the steroidogenic action by protection of .3′,5′-AMP, and (2) reductio...


Journal ArticleDOI
26 Nov 1966-Nature
TL;DR: The experiments described in this report were designed to estimate the amount of a radioactive dose of norethynodrel or ethynodiol diacetate which was excreted in the milk of rabbits and of humans.
Abstract: The amount of a radioactive dose of norethynodrel or of ethynodiol diacetate excreted in the milk of 2 rabbits and 4 women was investigated. The estrogenic activity of the milk extracts was too low to be detected by the mouse assay used. Very little of the radioactivity was transfered to the milk. The proportion of steroid that might appear in the milk if suckling was maintained might be larger than these experiments indicate.

Journal ArticleDOI
TL;DR: Un échantillon purifié de cholestérol-4-C14 a été absorbé par des feuilles de 2 plantes deDigitalis purpurea, environ 1% des métabolites globales a être constaté en forme de pregnénolone.
Abstract: Un echantillon purifie de cholesterol-4-C14 a ete absorbe par des feuilles de 2 plantes deDigitalis purpurea. Apres 18 jours on a extrait les plantes et separe les composes radioactifs. Environ 1% des metabolites globales a ete constate en forme de pregnenolone. Ainsi le cholesterol peut agir comme precurseur des sterols vegetaux.

Journal ArticleDOI
TL;DR: Newly ovulated eggs in cumulus, stained with toluidine blue, were transferred to the ampullae of the oviducts of mature rabbits 7 days after bilateral ovariectomy and treatment with progesterone and/or estradiol benzoate restored the rate of transport to the levels seen in estrous animals.
Abstract: Newly ovulated eggs in cumulus, stained with toluidine blue, were transferred to the ampullae of the oviducts of (a) 36 mature rabbits 7 days after bilateral ovariectomy, and (b) 13 intact mature rabbits. These rabbits received various doses of progesterone and/or estradiol benzoate (EB), dissolved in cotton seed oil and injected subcutaneously. The mean times (min) for the eggs to move from the base of the infundibulum to the junction of the ampulla and the isthmus were recorded, and subsequently converted in relation to the length of the ampulla to the mean rates of transport (mm/min). Ovariectomy decreased the mean rate of transport to 4.5 ± 0.8 mm/min, and this was not significantly further decreased (2.8 ± 0.4 mm/min) by daily treatment with 2 mg progesterone. Treatment with 2 and 4 /xg EB/day restored the rate of transport (8.4 ± 0.9 and 10.0 ±0.6 mm/min, respectively) to the levels seen in estrous animals. Progesterone injections (2 mg), which were given 13 hr before the observations on transport t...


Journal ArticleDOI
TL;DR: Because of racial differences in body hair, a comparison of plasma testosterone and urinary 17-ketosteroids in Japanese and occidental males and females was made.
Abstract: Because of racial differences in body hair, a comparison of plasma testosterone and urinary 17-ketosteroids in Japanese and occidental males and females was made. The Japanese women studied had been living either in Japan or in the United States for several years. All the males lived in the United States. There was no difference in the mean values of plasma testosterone of either males or females. No variation was shown in plasma testosterone in ambulatory subjects (6 males and 2 females) in specimens taken at 9 AM and 5 or 9 pm. The 17-ketosteroid excretion of the Japanese males was 6.2±1.0 (sd) mg/m2/24 hr and of the occidental males, 9.4±2.2 (sd) mg/m2/24 hr (p<.001). That of the Japanese females was 5.7±0.5 mg/m2/24 hr and of the occidental females, 7.7±1.9 (sd) mg/m2/24 hr (p<.005).

Journal ArticleDOI
01 Dec 1966-Steroids
TL;DR: The results indicate that inhibition may be substrate dependent which in turn might be energy linked, and the substrate specificity appears to involve endogenous pyridine nucleotide cofactors, particularly NADPH, as well as electron transport associated with steroid hydroxylation.


Journal ArticleDOI
03 Dec 1966-Nature
TL;DR: It takes about 3 to 4 days for eggs to reach the uterus after oestrus in most mammals, regardless of the length of the tubes, but in the rabbit the transport of eggs through the ampulla to the isthmus of the tube takes only a few minutes.
Abstract: IT takes about 3 to 4 days for eggs to reach the uterus after oestrus in most mammals, regardless of the length of the tubes1. In the rabbit the transport of eggs through the ampulla to the isthmus of the tube takes only a few minutes2,3, but 3–4 days4–6 are required for transport to the uterus. The eggs do not seem to be transported at the same speed during their passage through the whole tube, but they stop in the isthmus or in the uterine tubal junction and await some action of the tube which will transport them into the uterus.

Journal ArticleDOI
TL;DR: The pathway of sterol formation in fish is the same as in mammals but that it takes place in fish at a significantly slower rate, which indicates a major pathway through β, β-dimethylacrylic acid.

Journal ArticleDOI
TL;DR: The mechanization of the treatment of paper chromatograms with color reagents improves greatly the reproducibility of the results, the evenness and reproduCibility of background, and enables the successful use of color reactions which cannot be controlled sufficiently by manual methods to allow their quantitative estimation.


Journal ArticleDOI
TL;DR: Dimethyl sulfone has been detected and isolated from pasteurized cows'milk and the source of the sulfone is not yet known.
Abstract: SummaryDimethyl sulfone has been detected and isolated from pasteurized cows'milk. The source of the sulfone is not yet known. Dimethyl sulfoxide was not detected.

Journal ArticleDOI
TL;DR: The recovery of live albino fetuses from hooded recipients indicated that the contraceptive effect of clomiphene was not due to direct cytotoxic action on the developing zygote but to alteration of the maternal organism.
Abstract: Blastocysts from albino female rats that received a single, subcutaneous, nidation-inhibiting injection of clomiphene on Day 1 of gestation were transferred on Day 5 to the uteri of untreated, pseudopregnant hooded female rats or to the sterile uterine horns of unilaterally pregnant, untreated hooded female rats. The recovery of live albino fetuses from hooded recipients indicated that the contraceptive effect of clomiphene was not due to direct cytotoxic action on the developing zygote but to alteration of the maternal organism. This finding was further substantiated by (a) the failure of females injected with clomiphene to maintain the viability of blastocysts transferred to them from untreated females and by (b) the inhibition of decidual formation in pseudopregnant females after injection of a nidationinhibiting level of clomiphene. The amount of clomiphene necessary to prevent nidation by a single subcutaneous injection on Day 1 of gestation was 0.5 mg/kg body weight for Sprague-Dawley albino females...

Journal ArticleDOI
TL;DR: Parnate was the only drug that effected definite inhibition of the plasma enzyme and it was suggested that plasma monoamine oxidase titers can be used to monitor in vivo the effectiveness of monoamine oxidation inhibitor drugs.


Journal ArticleDOI
TL;DR: It is concluded that ferret eggs can survive and develop if introduced into the tubes of the rabbit but not into the uterus, whereas rabbit eggs cannot surviveIf introduced into either the ferret tube or uterus.
Abstract: Thirty-four 2–4 celled ferret eggs were transferred into Fallopian tubes of six 1-day pseudopregnant rabbits. Two days later ten normal 8–12 celled eggs without mucin coat of 15 transferred to three rabbits were recovered from their tubes and uteri. Four days after transfer none of 19 eggs transferred to the other three rabbits were found, indicating disintegration and disappearance of early ferret eggs in the rabbit uterus. Fifty-one ferret morulae or blastocysts were transferred into tubes of eight pseudopregnant rabbits. Examined two or four days later, four eggs from tubes were normal and expanded blastocysts. Of 25 eggs from uteri, nine (36%) were expanded and normal but 16 (64%) were expanded and degenerating. Fifty-eight ferret morulae or blastocysts were transferred into uteri of six 4-day pseudopregnant rabbits. Examined 2–4 days later all 45 recovered eggs were degenerated, showing incompatibility of ferret blastocysts in rabbit uteri. When 25 1-day rabbit eggs were transferred into ovarian capsules of three ferrets one and one-half days after an ovulation inducing injection no cleavage was observed in the eight eggs recovered from tubes and uteri. From 54 rabbit morulae or blastocysts transferred into uteri of six 6-day pseudopregnant ferrets, all 28 recovered eggs were degenerated and shrunken. No decidual reaction was observed either in rabbit or ferret endometrium. It is concluded that ferret eggs can survive and develop if introduced into the tubes of the rabbit but not into the uterus, whereas rabbit eggs cannot survive if introduced into either the ferret tube or uterus.