Synthesis and metabolism of vertebrate-type steroids by tissues of insects: A critical evaluation

Summary This review covers the synthesis and the metabolism of vertebrate-type steroids (progesterone, testosterone, estradiol, corticosteroids) by insect tissues and discusses the significance of the reactions for insect physiology. Biosynthesis of vertebrate-type steroids from cholesterol hitherto has been demonstrated in only two insect species, i.e. the water beetleAcilius sulcatus (Coleoptera) and the tobacco hornwormManduca sexta (Lepidoptera). InAcilius, steroid synthesis is associated with exosecretion (chemical defense). Nothing, however, is known about a physiological role of the C₂₁ steroid conjugate present in ovaries and eggs ofManduca. No synthesis of vertebrate-type steroids was observed in any other insect investigated to date. Most metabolic conversions of steroids by insects concerned oxidoreduction of oxygen groups (hydroxysteroid dehydrogenase activity) and (polar and apolar) conjugate formation. All important enzymatic steps involved in synthesis and catabolism, as known from studies with tissues of vertebrates, were not, or hardly observed. The conclusion is drawn that typical vertebrate-type (C₂₁, C₁₉ and C₁₈) steroids probably do not act as physiologically active substances in insects.     

In vitro metabolism of the trichothecene 4-monoacetoxyscirpenol by fungus- and non-fungus-feeding insects

Summary The metabolism of the trichothecene 4-monoacetoxyscirpenol by intact gut tissue was determined in the fungus-feeding Nitidulid,Carpophilus hemipterus (L.) and the non-fungus-feeding caterpillars, the fall armyworm,Spodoptera frugiperda (J. E. Smith) and the corn earworm,Heliothis zea (Boddie). The primary metabolite was the hydrolysis product scirpentriol. The amount of metabolism by theC. hemipterus larvae was ca 10 times that of the caterpillars on a per mg protein basis, suggesting metabolic adaptation for feeding on fungi that may contain mycotoxins.Acknowledgment. The authors wish to thank S. Taylor for technical assistance.The mention of firm names or trade products does not imply that they are endorsed or recommended by the U.S. Department of Agriculture over other firms or similar products not mentioned.     

The regulation of trehalose metabolism in insects

Trehalose is a non-reducing disaccharide comprising two glucose molecules. It is present in high concentration as the main haemolymph (blood) sugar in insects. The synthesis of trehalose in the fat body (an organ analogous in function to a combination of liver and adipose tissue in vertebrates) is stimulated by neuropeptides (hypertrehalosaemic hormones), released from the corpora cardiaca, a neurohaemal organ associated with the brain. The peptides cause a decrease in the content of fructose 2,6-bisphosphate in fat body cells. Fructose 2,6-bisphosphate, acting synergistically with AMP, is a potent activator of the glycolytic enzyme 6-phosphofructokinase-1 and a strong inhibitor of the gluconeogenic enzyme fructose 1,6-bisphosphatase. This indicates that fructose 2,6-bisphosphate is a key metabolic signal in the regulation of trehalose synthesis in insects. Trehalose is hydrolysed by trehalase (E.C. 3.2.1.28). The activity of this enzyme is regulated in flight muscle, but the mechanism by which this is achieved is unknown. Trehalase from locust, flight muscle is a glycoprotein bound to membranes of the microsomal fraction. The enzyme can be activated by detergents in vitro and by short flight intervals in vivo, which indicates that changes in the membrane environment modulate trehalase activity under physiological conditions.     

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.     

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.     

Blood-forming tissues in orthopteran insects: An analogue to vertebrate hemopoietic organs

Résumé Des cellules sanguines différenciées sont produites tout au long de la vic larvaire et imaginale des Insectes Orthoptères par des tissus hématopoïétiques spécialisés. Nos études morphologiques et expérimentales soulignent l'analogie que présentent ces tissus avec les organes hématopoïétiques des Vertébrés, à la fois sur le plan structural et sur la plan fonctionnel.     

Adenine nucleotide metabolism during anoxia and postanoxic recovery in insects

Severe hypoxia (anoxia), if maintained for more than a few minutes, causes irreversible damage in humans and other mammals. Why mammals are so vulnerable to anoxia is not fully understood. It is therefore of interest to study animals that are more tolerant of anoxia in order to identify physiological and metabolic properties that are correlated with a high tolerance of anoxia. Insects have high metabolic rates and their energy metabolism is dependent on aerobic ATP production. In insects, as in mammals, anoxia causes a rapid breakdown of physiological function, resulting in a state similar to rigor mortis. This is accompanied by a precipitous decrease in metabolic rate. In contrast to mammals, however, insects can survive anoxia for many hours and recover spontaneously and completely when air is again available. We have followed the metabolism of adenine nucleotides in locust tissues (mainly in the flight muscle) over 3 h of anoxia and during recovery from 1 h of anoxia. The content of ATP in the flight muscle dropped to 1% of normal during 2 h of anoxia. The main product was AMP which increased in content more than 20-fold. Some of the AMP was deaminated to IMP and this was further dephosphorylated to inosine. Altogether less than 30% of the total adenine nucleotides were degraded during 3 h of anoxia and this may contribute to the amazing ability of insects to recover from prolonged anoxia.     

Mouse models for human intestinal microbiota research: a critical evaluation

Since the early days of the intestinal microbiota research, mouse models have been used frequently to study the interaction of microbes with their host. However, to translate the knowledge gained from mouse studies to a human situation, the major spatio-temporal similarities and differences between intestinal microbiota in mice and humans need to be considered. This is done here with specific attention for the comparative physiology of the intestinal tract, the effect of dietary patterns and differences in genetics. Detailed phylogenetic and metagenomic analysis showed that while many common genera are found in the human and murine intestine, these differ strongly in abundance and in total only 4% of the bacterial genes are found to share considerable identity. Moreover, a large variety of murine strains is available yet most of the microbiota research is performed in wild-type, inbred strains and their transgenic derivatives. It has become increasingly clear that the providers, rearing facilities and the genetic background of these mice have a significant impact on the microbial composition and this is illustrated with recent experimental data. This may affect the reproducibility of mouse microbiota studies and their conclusions. Hence, future studies should take these into account to truly show the effect of diet, genotype or environmental factors on the microbial composition.     

Sterol metabolism in insects and biosynthesis of ecdysone in the silkworm

Cellular and Molecular Life Sciences -     

Potential juvenile hormone analogues containing piperidine ring: Synthesis and biological assay on insects

Summary Some compounds containing piperidine rings have been synthesized, and submitted to biological tests on insects for their hormonal activity on pupae ofTenebrio molitor L. andBombyx mori L. Some of them display a hormoneanalogue or toxic activity.The editors do not hold themselves responsible for the opinions expressed in the authors' brief reports. — Les auteurs sont seuls responsables des opinions exprimées dans ces brèves communications. — Für die Kurzmitteilungen ist ausschliesslich der Autor verantwortlich. — Per le brevi comunicazioni è responsabile solo l'autore. — . — Solo los autores son responsables de las opiniones expresadas en estas comunicationes breves.This research has been supported by the Italian National Research Council (CNR) special ad hoc program Fitofarmaci e Fitoregolatori, Subproject. 7.Acknowledgments. We thank Prof. G. Jommi for helpful discussions related to this and previous articles on the same subject.     

GPR120: a critical role in adipogenesis,inflammation, and energy metabolism in adipose tissue

It is well known that adipose tissue has a critical role in the development of obesity and metabolic diseases and that adipose tissue acts as an endocrine organ to regulate lipid and glucose metabolism. Accumulating in the adipose tissue, fatty acids serve as a primary source of essential nutrients and act on intracellular and cell surface receptors to regulate biological events. G protein-coupled receptor 120 (GPR120) represents a promising target for the treatment of obesity-related metabolic disorders for its involvement in the regulation of adipogenesis, inflammation, glucose uptake, and insulin resistance. In this review, we summarize recent studies and advances regarding the systemic role of GPR120 in adipose tissue, including both white and brown adipocytes. We offer a new perspective by comparing the different roles in a variety of homeostatic processes from adipogenic development to adipocyte metabolism, and we also discuss the effects of natural and synthetic agonists that may be potential agents for the treatment of metabolic diseases.     

Sphingolipid metabolism and its role in the skeletal tissues

The regulators affecting skeletal tissue formation and its maintenance include a wide array of molecules with very diverse functions. More recently, sphingolipids have been added to this growing list of regulatory molecules in the skeletal tissues. Sphingolipids are integral parts of various lipid membranes present in the cells and organelles. For a long time, these macromolecules were considered as inert structural elements. This view, however, has radically changed in recent years as sphingolipids are now recognized as important second messengers for signal-transduction pathways that affect cell growth, differentiation, stress responses and programmed death. In the current review, we discuss the available data showing the roles of various sphingolipids in three different skeletal cell types—chondrocytes in cartilage and osteoblasts and osteoclasts in bone. We provide an overview of the biology of sphingomyelin phosphodiesterase 3 (SMPD3), an important regulator of sphingolipid metabolism in the skeleton. SMPD3 is localized in the plasma membrane and has been shown to cleave sphingomyelin to generate ceramide, a bioactive lipid second messenger, and phosphocholine, an essential nutrient. SMPD3 deficiency in mice impairs the mineralization in both cartilage and bone extracellular matrices leading to severe skeletal deformities. A detailed understanding of SMPD3 function may provide a novel insight on the role of sphingolipids in the skeletal tissues.     

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).     

Genetic factors in neurotoxicology and neuropharmacology: A critical evaluation of the use of genetics as a research tool

Animals have evolved a detoxication system to enable them to survive in a hostile chemical environment in which foods contain many non-nutrient chemicals. Detoxication depends on enzymes which are often genetically polymorphic. As a result, inter-individual variation is common, and in humans several Mendelian loci have been identified. However, most variation in response is probably due to the action of several genes. Genetic variation in response to the neurotoxin MPTP and to chemically and physically-induced seizures is reviewed. In the former case, differences between pigmented and white mouse strains have been noted which are consistent with the hypothesis that humans are more sensitive than mice or rats because of the presence of melanin in human brains. However, variation in sensitivity probably also depends on other genes. In the case of audiogenic seizures, a single locus has been identified and mapped, but its relationship with seizures induced by other agents is not clear. Genetic variation in response to alcohol is also discussed. The failure of most toxicologists to consider genetic variation as a potentially confounding variable, and as a powerful research tool, is discussed critically in relation to non-repeatability of research on the neurotoxic effects of lead, and in relation to the genetic variation in MPTP, seizures, and alcohol response already noted. It seems clear that genetic methods provide a powerful research tool which is largely being ignored by toxicologists.     

Allergic encephalomyelitis: Inhibition of cellular passive transfer by exogenous and endogenous steroids

Zusammenfassung Injektionen des Antientzündungssteroids Dexamethasone oder eine Hypersekretion des endogenen Kortikosteroids als eine Reaktion zum unspezifischen Stress verhindern die zelluläre passive Übertragung allergischer Enzephalomyelitis. Deshalb kann angenommen werden, dass Steroide die enzephalitogene Wirkung von vollkommen immunisierten Lymphoidzellen verhindern.

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Supported by National Multiple Sclerosis Society grant No. 536A10 and United States Public Health Service grant No. HD 02261-03. R.Sowinski and B. H.Brown assisted in the experiments. Dr. H. B.Devlin, Parke Davis & Co., Detroit, kindly supplied the pertussis vaccine.