Allene versus acetylene in progestational steroids

Zusammenfassung Die Einführung einer Allengruppe an Stelle der üblichen Acetylen-Seitenkette in konzeptionsverhütenden 19-nor-Testosteronderivaten ergibt eine überraschende Steigerung der gestagenen Wirksamkeit. Eine analoge Modifikation typischer Östrogene wie Mestranol beeinflusst die östrogene Wirksamkeit nur unwesentlich.     

11 beta-methyl-19-norsteroids: novel progestational hormones

The synthesis and biological properties of 2 11beta-methyl-19-norsteroids (17alpha-ethynyl-17beta-hydroxy-11beta-methylestr-4en-3-one and 3beta, 17beta-diacetoxy-17alpha-ethynyl-11beta-methylestr-4-ene) are described. In experimental animals both compounds exhibited potent progestational activities, antiestrogenic activities, and estrogenic responses in the estrogen-deficient state. It is suggested that the latter compound may be similar to other progestational agents in failing to alter hepatic excretory function and may possess anovulatory properties without some of the side effects associated with steroid contraceptives presently employed.     

11β-methyl-19-norsteroids: Novel progestational hormones

Zusammenfassung Die Synthese von 3, 17-Diacetoxy-17-Äthinyl-11-Methylestr-4-en (XII) wird beschrieben. Die Substanz besitzt besonders starke Antifertilitätseigenschaften, wie sie sonst nur Mischungen von Hormonen eigen sind, welche für die Humanfertilität benutzt werden, jedoch ohne deren Nebenwirkungen.     

Pre-menstrual steroids

A number of steroid hormones and their metabolites fluctuate in the circulation across the human menstrual cycle. In addition to their classic actions on the hypothalamo-pituitary-gonadal axis, many of these hormones act as 'neuroactive steroids' to alter the function of neurotransmitters, such as GABA, within central nervous system circuits. Clinically, these steroids are important because they have not only acute but also long-term effects, and 'withdrawal' properties. This review discusses the effects of steroids such as 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP or allopregnanolone) which alter GABA function in distinct ways dependent upon the time course of exposure, to either enhance or decrease inhibition in the brain. These effects are discussed in light of recent clinical findings which seek to further characterize the steroid milieu which underlies pre-menstrual dysphoria.     

Action of various progestational hormones on the electric activity of the rat myometrium in pregnancy after biovariectomy

8-day-pregnant rats were ovariectomized, then injected im with progestagens and estrogens while their uterine motility and electrical activity were being recorded simultaneously with a strain gauge and 2 bipolar electrodes. The injections, known to maintain pregnancy after ovariectomy, were progesterone 50 mg/kg, progesterone with estradiol 5 mcg/kg, or medroxyprogesterone acetate 25 mg/kg. Base line recordings for 20 minutes showed the normal pregnant state of brief periods of synchromous electrical and mechanical activity. After ovariectomy, untreated controls exhibited increased duration of synchronized mechanical and electrical activity and height of contractions. When any of the 3 progestagen treatments coincided with ovariectomy, synchrony was decreased and the intervening interval lasted longer. These procedures demonstrated how quickly the hormonal deficit due to ovariectomy is compensated for when ablation is performed before placental progesterone synthesis has begun.     

Conversion of steroids by microorganisms

Zusammenfassung Die methodischen Grundlagen der Umwandlung von Steroiden durch Mikroorganismen werden diskutiert, insbesondere die apparativen Erfordernisse, die Kulturbedingungen sowie der Nachweis und die Isolierung der Reaktionsprodukte. Die Umsetzungen mit Enzymen aus Mikroorganismen werden denjenigen mit Nebennieren-Enzymen gegenübergestellt.Von mikrobiologischen Reaktionen stehen Hydrierungen, Dehydrierungen und besonders Hydroxylierungen an verschiedenen Stellen der Steroidmolekel im Vordergrund. Im weiteren wurde auch Abbau der Seitenkette von Pregnanderivaten, der mit Ringspaltung und/oder mit Dehydrierung in 1-Stellung einhergehen kann, festgestellt. Die Einführung dieser Doppelbindung wird speziell besprochen.

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From a lecture at the 128^th National Meeting of the American Chemical Society, Minneapolis, Minn.; Symposium on Metabolic Conversions of Steroids; September 16, 1955. Communication No. 136 On Steroids. No. 135 compareE. Vischer, J. Schmidlin, andA. Wettstein, Exper. (in press).     

Heterocyclic steroids. Steroidal pyrimidines

Zusammenfassung Die erste Synthese eines Steroid-Analogen, in welchem Ring A zu einem Pyrimidin umgewandelt wurde, wird beschrieben. Die wichtigste Zwischenstufe 4b wurde durch Abbau von 19-nor-Testosteron gewonnen. Kondensation von 4b mit Thioharnstoff führte zu 17-Acetoxy-2,4-diazaestr-4-en-1-on-3-thion (5).

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(a) This research was supported by U.S. Public Health Service Grant No. A-5326; (b) Part IV of Heterocyclic Steroids. Part III, seeE. Caspi, P. K. Grover, andD. M. Piatak, Chem. and Ind., in press.

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Recipient Public Health Service Research Career Program Award CA-K3-16614 from the National Cancer Institute.     

The role of glycine in the biosynthesis of steroids

Zusammenfassung Während der Biosynthese von Cholesterol mit homogenisierter Rattenleber wird [2-¹⁴C] des Glycins viel besser eingebaut als [1-¹⁴C].Saccharomyces cerevisiae produziert radioaktives Squelen (ausser Ergosterol mit Radioaktivität des Ringsystems) mit [2-¹⁴C] Glycin und mit [3-¹⁴C] Serin, aber nicht mit [1-¹⁴C] Glycin.

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Studies on Biosynthesis. Part VI. For Part V, seeA. K. Bose, K. S. Khanchandani andB. L. Hungund, Experientia,27, 1403 (1971). b) Presented at the 164th National Meeting of the American Chemical Society, New York, August, 1972.

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The support of this research by Stevens Institute of Technology and Sandoz Foundation is gratefully acknowledged. We wish to thank Drs.P. T. Funke, M. S. Manhas, P. K. Bhattacharyya, M. Anchel andH. Levey for valuable discussions and help with some of the experiments.     

Guggulsterol-like steroids from the Mediterranean gorgonianLeptogorgia sarmentosa

Summary Several polyoxygenated steroids (1, 2, 3) have been isolated from the marine gorgonianLeptogorgia sarmentosa. One of these (1) is the known guggulsterol III, previously found in the pharmacologically active resin from the treeCommiphora mukul; the others,2 and3, have not been found before in nature, and are closely related to1. During the structural work apparent anomalies in the CMR-spectra of1 were observed.The authors are grateful to Prof. Sukh Dev for the PMR-spectra of guggulsterol III. Thanks are also due to Zoological Station (Naples), for the collection of the gorgonian, to Centro Metodologie Chimico-Fisiche, Università di Napoli, for recording PMR-spectra on WH-270 Superconducting Spectrometer-Bruker, to Mr C. Di Pinto for the CMR-spectra and to Mr A. Milone for the MS spectral measurements.     

Sexual steroids and monoamine metabolism during gestation

Summary The experiments show influence of progesterone and estradiol on regulation of enzymes of monoamine metabolism, MAO and COMT during pregnancy. Both the hormones inhibit enzymes MAO and COMT in the adrenals when determined at 0 h parturition. Estradiol has stronger inhibitory effect than progesterone. The results provide evidence for important endocrine implication during pregnancy for processes of monoamine regulation.The generous help of Dr.Raynaud of CEA, France is gratefully acknowledged. A.R.B. is pre-doctoral fellow of Paris University.     

On the biosynthesis of testicular steroids in vitro and its inhibition

Zusammenfassung Der Seitenkettenabbau von C₂₁-Steroiden zu Androgenen in Rattentesteshomogenat erwies sich abhängig von der Konzentration der Vorstufen und konnte durch gewisse Pyridinderivate präferentiell blockiert werden.     

The involvement of porphyrogenic steroids in the development of experimental porphyria

Summary Hexachlorobenzene alters the hepatic steroid metabolism, and it was suggested that a porphyria was induced by overproduction of 5-H-steroids. Structurally similar chlorinated hydrocarbons (pentachlorobenzene, pentachlorophenol, 2,4,5-trichlorophenol) without porphyrogenic activity did not affect the steroid metabolism in rat liver.Dedicated to Prof. Dr. L. Róka on the occasion of his 60th birthday.     

Sex steroids in the rat submaxillary gland during the estrus cycle

Relatively high progestagen levels were found in female rat submaxillary glands, with a maximum in the proestrus stage at 22 h and 2 minima; in proestrus between 10 and 14 h, and in estrus at 14 h. Estrogen and androgen concentrations in the gland were undetectable during most of the cycle except in the proestrus stage, when the highest level was determined at 14 h for estrogens and at 17 h for androgens.     

Sexual steroids and monamine metabolism during gestation.

The experiments show influence of progesterone and estradiol on regulation of enzymes of monamine metabolism, MAO and COMP during pregnancy. Both the hormones inhibit enzymes MAO and COMPT in the adrenals when determined at 0 h parturition. Estradiol has stronger inhibitory effect than progesterone. The results provide evidence for important endocrine implication during pregnancy for processes of monamine regulation.     

Preparation and androgenic activity of novel heterocyclic steroids

Zusammenfassung Die Darstellung verschiedener A-Nor-5-androstan-Verbindungen, die im A-Ring ein Schwefel-, Selen- oder Tellur-Atom haben, wird beschrieben. Sie besitzen, im Gegensatz zu den entsprechenden Oxa-Verbindungen, anabol-androgene Aktivität. 2, 3-Dithia-5-androstan-17-ol-Acetat hatte ebenfalls hohe anabol-androgene Wirksamkeit. Daraus wird geschlossen, dass fÜr die anabol-androgene Aktivität, nicht die elektronischen, sondern die sterischen Eigenschaften der C-2 und C-3 Atome, beziehungsweise ihre Substituenten, von Bedeutung sind.