Showing papers by "Worcester Foundation for Biomedical Research published in 1956"
TL;DR: Norethynodrel and norethisterone had identical effects; endometria showed stimulated stromal but retarded glandular development and exhibited menstruallike bleeding between cycles and Ethyl-19-nortestosterone however permitted only breakthrough bleeding in 8 of 16 women.
Abstract: Preliminary trials of 17alpha-ethinyl-19-nortestosterone (norethynodrel) 17alpha-ethinyl-5(10)-estraeneolone (norethisterone) and 17alpha-ethyl-19-nortestosterone in 50 infertile women are described. Patients were 22-39 years old (mean 29) ovulating and menstruating regularly but infertile for 1.5-6 years. They took 5-50 mg of one of the progestagens from Cycle Days 5-25 for a total of 112 cycles. Cycle length endometrial biopsies basal temperature vaginal smears and pregnanediol excretion were monitored. In only 2 cycles with norethisterone were any 2 of these criteria suggestive of ovulation but pregnediol remained .1 mg/day (an ovulatory range). In most respects norethynodrel and norethisterone had identical effects; fo r example endometria showed stimulated stromal but retarded glandular development and exhibited menstruallike bleeding between cycles. Ethyl-19-nortestosterone however permitted only breakthrough bleeding in 8 of 16 women. All 3 compounds inhibited ovulation in doses above 10 mg daily. 7 (15%) women conceived within 5 months after the trial including 5 who had been infertile for 3-6 years.
105 citations
TL;DR: The progestational activity of the various compounds was tested by theClauberg (6) method and effects on development of the ovulated ovum were studied.
Abstract: IN PREVIOUS publications a number of compounds have been demonstratedas inhibitors of ovulation in rabbits and rats (1, 2, 3). As ourstandard of reference we have used progesterone, which appears to beeffective also in women (4,5). Of especial interest are four compounds:17a-ethinyl-19-nortestosterone (I), 17a-ethinyl-5(10)estraen-17/3-ol-3-one(II), 17a-ethyl-19-nortestosterone (III), and 17a-methyl-19-nortestosterone (IV). These compounds have been suudied for: (a) progestational activity inrabbits, (b) deciduomagenic capacity in rats, (c) estrogenic activity, (d)ovulation-inhibiting activity in rabbits and rats, and (e) effects on developmentof the ovulated ovum. Progestational activity in rabbits The progestational activity of the various compounds was tested by theClauberg (6) method. Immature, grey Chinchilla, female rabbits weighingapproximately 1 kg. were used in this study.
100 citations
TL;DR: The results of an experiment in vitro carried out to study the possible biochemical conversion of testosterone to estrogenic steroids by human ovarian tissue are reported.
95 citations
89 citations
TL;DR: A group of substances which by reason of certain similarities to progesterone may be classified as progestins, which appears to have typical progesteronelike activity in all of the tests but it is quantitatively more active than progester one in the Clauberg assay and in deciduomagenic activity and less active in the others.
Abstract: The effects of certain 19-norsteroids on reproductive processes in mammals are presented. 17alpha-ethinyl-19-nortestosterone 17alpha-ethinyl-5(10)estraeneolone 17alpha-ethyl-19-nortestosterone 17alpha-methyl-19-nortestosterone and progesterone were studied using the Clauberg assay in rabbits the Rubin assay in mice the deciduomagenic activity in rats the conception-inhibiting activity in rats and in the ability to induce and sustain implantation of fertilized ovum in female rabbits castrated 1 day after a fertile mating. These studies reveal a group of substances which by reason of certain similarities to progesterone may be classified as progestins. 17alpha-ethyl-19-nortestosterone appears to have typical progesteronelike activity in all of the tests but it is quantitatively more active than progesterone in the Clauberg assay and in deciduomagenic activity and less active in the others. Normal reproductive processes such as ovulation may be inhibited or stimulated such as endometrial proliferation with these compounds.
67 citations
65 citations
57 citations
TL;DR: The authors have attempted to summarize the more important literature pertaining to the human fetal adrenal and a histologic correlation with the chemical data of the preceding paper is presented.
Abstract: THE unusually large size of the adrenal glands of the human fetus (Figs. 1, 2) and their rapid partial involution have been the subject of numerous reports and investigations. Lanman (1953) contributed an admirable summary of all known details concerning the development and probable function of this gland in the developing human fetus and added a valuable comparative anatomic study of the adrenals in other animals. While a wealth of contributions to the literature is cited by Lanman (19.53), his conclusion is that little definite is known regarding the actual physiology of the adrenal in the unborn human fetus. In this communication the authors have attempted to summarize the. more important literature pertaining to the human fetal adrenal. In addition, a histologic correlation with the chemical data of the preceding paper is presented. On the basis of this material and evidence derived from the literature the endocrine relations are discussed which are of probable significance in the maintenance and func...
50 citations
46 citations
TL;DR: Experiments were conducted to determine the excretion of adrenaline (A) and noradrenaline (NA) in sleep and in waking states and after the infusion of A and NA into an adrenalectomized subject.
Abstract: The pressor substance in normal human urine demonstrated by Holtz et al. (1) was considered by them to be a mixture of adrenaline, noradrenaline and hydroxytyramine. A few years later Von Euler ect al. (2, 3) succeeded in separating all three amines from urine extracts by the use of chromatographic techniques. In a preceding paper (4) we reported observations regarding the nature of the adrenaline and noradrenaline in normal human urine. The present report concerns experiments which were conducted to determine the excretion of adrenaline (A) and noradrenaline (NA): 1) in sleep and in waking states; 2) after the infusion of A and NA into an adrenalectomized subject; 3) after psychomotor stress, operating the Hoagland-Werthessen pursuitmeter (5) under normal and hypoxic conditions; and 4) after the administration of ACTH.
39 citations
TL;DR: In contrast to the available data on the morphology and anatomy of the human fetal adrenal cortex, its physiology remains largely unknown.
Abstract: THE embryological development of the human fetal adrenal cortex, and, perhaps, other primates, is unique. During the second month of fetal life, a distinct adrenal cortex is recognized. It reaches its largest relative size during the third and fourth month when it occupies about 0.5% of the total body volume as compared to 0.01% in the adult (Jackson, 1909). The histological picture of the fetal adrenal cortex differs from that of the adult by the presence of the fetal zone, which comprises about 80% of the whole cortex. The fetal zone degenerates rapidly during the first post-natal months. In addition, only the glomerular and fascicular zones of the cortex are fairly well developed in the fetus (Lanman, 1953). In contrast to the available data on the morphology and anatomy of the human fetal adrenal cortex, its physiology remains largely unknown. An excellent review of the subject has been published by Lanman (1953). Large amounts of ascorbic acid (Bourne, 1933) and lipid material (Lanman, 1953) have bee...
TL;DR: Five transformation products were isolated and identified and the specific activity of the isolated products was of the same order of magnitude as the starting steroid precursor; this indicates that there was no dilution of the radioactive materials by endogenous precursors.
TL;DR: Hormonal requirements at implantation vary from those needed for subsequent development, and the number of implantations did not increase with the transplantation of ova, which may suggest a quantitative basis for the hormonal requirement at implants.
Abstract: SummaryThe role of ovarian hormones in implantation was studied in rabbits ovariectomized after mating and in ovariectomized pseudopregnant rabbits into which fertilized ova were transplanted. There was no evidence of delayed implantation. One to 3 implantations occurred in ovariectomized rabbits injected with 2 or 25 mg progesterone. The percentage of implantations ranged from 15 to 23 irrespective of dosage or the time at which injection started. Implantation failed to occur when the dose was 0.3 mg progesterone or 0.1 mg estradiol in combination with progesterone. The number of implantations did not increase with the transplantation of ova. This may suggest a quantitative basis for the hormonal requirement at implantation. Hormonal requirements at implantation vary from those needed for subsequent development.
01 Jan 1956
TL;DR: It is shown that small doses of cortisone used in conjunction with licorice were quite effective in maintaining the electrolyte balance in adrenal deficiency states, and suggested that those cases of Addison's disease which did respond toLicorice still had remnants of functional adrenocortical tissue.
Abstract: Molhuysen et al. (1) demonstrated that licorice extract taken orally by human subjects acted on the electrolyte balance in a manner similar to that of desoxycorticosterone acetate, namely, with theretention of sodium and the excretion of potassium. Groen and his associates (2, 3, 4) extended these findings to demonstrate that glycyrrhizinic acid1 and its hydrolysis product, glycyrrhetic acid obtained from licorice,were the active ingredients of the extract. Though Groen et al. had some success in the maintenance of patients with Addison's disease on licorice preparations, Borst and his associates (5) noted that these preparationsin a case of Addison's were ineffective when used alone. However, they did note that small doses of cortisone used in conjunction with licorice were quite effective in maintaining the electrolyte balance in adrenal deficiency states, and suggested that those cases of Addison's disease which did respond to licorice still had remnants of functional adrenocortical tissue (5). Recentl...
TL;DR: The high respiratory rate of blastocysts was associated with the morphological changes yet the rate of increase was not directly proportional to cell mass increase, and it is suggested that these pacts reflect a change in metabolic pathways.
Abstract: SummaryRespiration of fertilized rabbit eggs (intact, punctured or dissected) in different pre-implantation stages was measured in the Cartesian diver and Warburg apparatus. Average O2 uptake of eggs 16, 40, 65, 90, 120, 140 and 160 hr post-coitum was 0.61, 0.51, 0.48, 2.56, 200, 400 and 800 mμl/ovum/hr respectively. The high respiratory rate of blastocysts was associated with the morphological changes yet the rate of increase was not directly proportional to cell mass increase. It is suggested that these pacts reflect a change in metabolic pathways. Intact blastocysts (in Warburg) respire at a lower rate than punctured ones due to the bicarbonate content of blastocyst fluid which raised the pH in the CO2-free atmosphere. Cumulus cells respire at a high rate while the zona pellucida does not respire at all.
TL;DR: The results obtained by the perfusion of three such steroids, viz., corticosterone, desoxycortic testosterone, and progesterone, form the subject matter of this communication.
Abstract: WETTSTEIN and co-workers (1955) described the formation of material possessing the chromatographic and biological properties of aldosterone by incubation of desoxycorticosterone with adrenal homogenates. In addition, it was shown that corticosterone, progesterone and pregnenolone decreased the yield of aldosterone under the same conditions. Since we have been able to demonstrate the presence of an aldosteronelike material in the effluent of isolated calf adrenal glands perfused with a synthetic perfusion medium (Ungar et al., 1954), this technique has been employed to study the byconversion of possible steroid precursors to aldosterone. The results obtained by the perfusion of three such steroids, viz., corticosterone, desoxycorticosterone, and progesterone, form the subject matter of this communication.
TL;DR: A study was undertaken to evaluate the sympathico-adrenal response of normal male subjects by measuring the excretion of epinephrine (E) and norepinephrine (NE) and measuring the nature and quantity of the catechol amines secreted after the administration of the insulin and methacholine.
Abstract: Hypoglycemia and hypotension are known to cause stimulation of the sympathico-adrenal system (1). Using insulin as the hypoglycemic agent and methacholine (Mecholyl®) as the hypotensive drug, a study was undertaken to evaluate the sympathico-adrenal response of normal male subjects by measuring the excretion of epinephrine (E) and norepinephrine (NE). In the infusion experiments with E and NE, graded doses were used. Control experiments with physiologic saline were run for thirty minutes when estimations of the excretion rate of catechol amines were made. The results of the latter experiments and those previously published on adrenalectomized subjects (2) were used for evaluation of the nature and quantity of the catechol amines secreted after the administration of the insulin and methacholine. Blood pressure and pulse rate were determined in all experiments.
TL;DR: Ethyl acetate extracts of human urine have been analyzed by the use of paper chromatography for polar reducing corticosteroids and 6β-Hydroxycortisol (as diacetate) has been isolated in crystalline form from urinary extracts of normal men with and without cortisol feeding.
TL;DR: The studies on the conversion of HT to norepinephrine-like material (HELM) by beef adrenal acetone powder and several species of molds are reported, finding the calorimetric methods used are not beyond criticism.
TL;DR: In this article, the changes in urinary 17-ketosteroid excretion with increasing age have been investigated and the recovery of orally administered steroids as individual urinary 17ketosteroids was determined.
Abstract: Extensive biologic and clinical investigations of the process of aging have demonstrated a general decrease in testicular activity with increasing age. With the recent elaboration of adequate chemical methods (primarily chromatographic techniques (1–6)) for the determination of androgenic and related steroids (C19) or corticoids (C21 steroids) estimates of hormonal synthesis and release by the testis and adrenal have become possible. Particular application of chromatography, and especially paper chromatography, has been made to systematic studies of the changes in urinary 17-ketosteroid excretion with increasing age (7–10). On the basis of results from such studies and from experiments in which the recovery of orally administered steroids as individual urinary 17-ketosteroids was determined (11), approximate values have been calculated for the daily secretion of androgens and corticosteroids in men and women (12).
TL;DR: Ein LSD-ähnliches Stoffwechselprodukt ist möglicherweise mit Geisteskrankheit gekoppelt, wird vorgeschlagen.
Abstract: Ein LSD-ahnliches Stoffwechselprodukt ist moglicherweise mit Geisteskrankheit gekoppelt Eine Biosynthese der Lysergsaure und ihrer Derivate, die Tryptophan und α-Ketoglutarsaure als wichtige Intermediarprodukte enthalt, wird vorgeschlagen
TL;DR: The presence of a pressor substance (urosympathin) in the urine of normal man was demonstrated to be a mixture of adrenaline, noradrenaline, and the relatively inactive hydroxytyramine, which was separated by means of chromatographic techniques.
Abstract: Holtz et al. (1), using acid hydrolysis, demonstrated the presence of a pressor substance (urosympathin) in the urine of normal man. Closer examination of the urine extract indicated that this pressor substance was a mixture of adrenaline (A), noradrenaline (NA), and the relatively inactive hydroxytyramine (2, 3). Von Euler et al. (3) separated these amines by means of chromatographic techniques and showed that the normal amounts of these substances were 0.1–0.2 mg. per day for hydroxytyramine, 20–60 μg. per day for NA, and 1–8 μg. per day for A.
TL;DR: It has been found by Sinex (1954) that prior treatment of intact rats with ACTH will cause a decrease in the in vitro incorporation of alanine-1-C14 into liver slices.
Abstract: IT IS known that many steroid hormones affect both protein metabolism (Rutgers University Protein Symposium, 1953) and the formed elements of the blood (Gordon, 1954). Thus, the administration of ACTH results in an increase in urinary amino acids (Ronzoni et al., 1953) and adrenalectomy of the eviscerated rat causes a decrease of plasma amino acids (Ingle et al., 1950). Barton and Rusch (1951) have shown that administration of adrenocortical extract inhibited the in vivo incorporation of glycine-2-C14 into several tissue proteins. Similarly, it has been found by Sinex (1954) that prior treatment of intact rats with ACTH will cause a decrease in the in vitro incorporation of alanine-1-C14 into liver slices.
TL;DR: The presence of a steroid C-20α-reductase has been demonstrated in hog liver brei by the isolation and identification of Δ 4 -pregnene-20 α, 21-diol-3-one and Δ 4-pregnenes-17α, 20α,21-triol- 3-one after the incubation of 11-deoxycorticosterone and 11- deoxyCortisol, respectively.
TL;DR: It was shown that the steroids conjugate was hydrolyzed by a commercial preparation of β-glucuronidase (Warner-Ketodase) of unknown purity, and it was established that the steroid moiety of the conjugates was testosterone.
TL;DR: DOC does inhibit the oxygen consumption of reticulocyte preparations, but not to a degree sufficient to account for its inhibition of glycine-C 14 incorporation.