▼ 1.1. A number of sterols excreted by the baboon (Papio papio) and the Rhesus monkey (Macaca mulatto) have been identified. 2.2. The pattern of sterols was similar in both species. In the Rhesus monkey the cholesterol group contributed 39.7 per cent of the total sterols, the campesterol and stigmasterol group contributed 16.6 per cent, and the β-sitosterol group contributed 43.6 per cent. In the baboon they contributed 46.8, 14.9, and 38.2 per cent respectively. 3.3. The 5β-stanols constituted the major fraction in the faeces (65-86 per cent) in both species. Coprostigmastanol was the major faecal sterol in both species. 4.4. 5α-Stanols contributed 9-11 per cent of the total in both species and stigmastanol was the major component.

▼ The uptake of steroids by human red blood cells was investigated with an incubation technique and with equilibrium dialysis, and the following observations were made: (1) In the sequence pregnenolone, 20α-dihydroprogesterone, testosterone, androstenedione a decrease in binding affinity of erythrocytes suspended in Krebs-Ringer-bicarbonate buffer was observed. The ratio of bound to unbound steroid did not vary significantly with the steroid concentration. Most of the bound steroid was removed by washing the red blood cells several times with isotonic buffer, indicating that steroids might be adsorbed to the cell surface.: 1.(2) The percentage of progesterone bound to erythrocytes in a 5% (v/v) plasma solution increased with increasing concentrations (0-75 ng/ml) of progesterone. With progesterone concentrations > 75 ng/ml the distribution of progesterone between the plasma proteins and erythrocytes remained constant. In studies with the whole blood 25-30% of added [^3H]-pregnenolone was bound to the red blood cells, but only 0-10% [^3H]-progesterone was bound to the erythrocytes. 2.(3) Experiments on the reduction rate of DHA and DHA sulfate, and of estrone and estrone sulfate, by intact and hemolysed human erythrocytes indicate a difference in permeability of the intact cell membrane for steroid sulfates and the corresponding free steroids. 3.(4) In binding studies with a total hemolysate, most of the steroid was associated with proteins of the membrane-free hemolysate and only a small fraction was bound to the membrane. The combining affinity, expressed as the ratio of bound to unbound steroid per unit amount of protein was higher for hemoglobin-free membranes than for a membrane-free hemolysate. The binding of testosterone and progesterone by a soluble protein fraction from erythrocyte membranes is higher than could be expected on the basis of dialysis studies with intact membranes. Testosterone was bound in a specific way by a fraction from a membrane-free hemolysate. containing 17β-hydroxysteroid dehydrogenase activity. An apparent association constant for binding of testosterone by this fraction was found to be in the order of magnitude of 10^8 I (mol protein)^-^1. The testosterone-binding fraction isolated from the membrane-free hemolysate was further characterized with gel chromatography. The results of these studies suggest that the uptake of steroids by intact erythrocytes can be explained in terms of (a) adsorption and/or binding to the membrane, (b) diffusion into the cell, and (c) binding inside the cell.

▼ 1.1. The presence of steroid-converting enzymes in different brain areas as well as the subcellular distribution of these enzymes have been studied. 2.2. Identification of metabolites following incubations of various steroids with brain tissue indicated that 5α-steroid reductase (EC 1.3.1.99) and 3α- and 17β-hydroxysteroid dehydrogenases (E.C. 1.1.1.50 and EC 1.1.1.51) are present. 3.3. The subcellular localizations of these steroid-converting enzymes were studied with ultracentrifugation techniques. From the comparison of the specific activities of steroid-converting enzymes with marker enzymes (NADH-cytochrome c reductase and lactate dehydrogenase) and other characteristic parameters (RNA, DNA and protein content) it was concluded that hydroxysteroid dehydrogenases are present in the soluble fraction and the 5α-steroid reductase in the microsomes. 4.4. Ratios of the specific activities of 5α-steroid reductase in different brain tissues relative to the specific activity in total brain were: hypophysis, 0.3; hypothalamus, 1.0; cerebellum, 1.6; cortex, 0.3. No significant differences were found between the specific activities of 17β-hydroxysteroid dehydrogenase in the different brain tissues.

▼ Sheep fetal blood cells contain an active 17β-hydroxy steroid oxidoreductase which catalyses the interconversion of estrone and estradiol-17β and may play an important role in the metabolism of estrogens in the sheep fetal-placental unit.

▼ 

Summary

After a brief review of the literature on the effect of hormones upon resistance, the fundamental differences between “syntoxic” and “catatoxic” hormones are discussed. The former (e.g., glucocorticoids) do not exert an effect on the aggressor itself but merely suppress morbid tissue reactions (e.g., inflammation). By contrast, catatoxic hormones do not affect tissue reactions but accelerate the degradation of pathogenic substances. Usually, the degradation products are less toxic than the original poisons and, if so, catatoxic hormones exert a protective effect.

The most recent experiments, described here in detail, showed however that the protective effect of catatoxic hormones, e.g., that of pregnenolone-16α-carbonitrile (PCN) and spironolactone (SNL) against digitoxin and indomethacin, are blocked by concurrent treatment with triamcinolone and thyroxine. In this respect, estradiol is effective only against digitoxin. This type of true “anticatatoxic” action does not depend upon the steroid structure of the agents since desoxycorticosterone (DOC), progesterone and hydroxydione fail to antagonize the protective effect of PCN or SNL against either digitoxin or indomethacin, whereas thyroxine is effective in this regard.

▼ 1.1. An in vitro test is described for assaying tissue extracts for ''metabolic hormone'' in Pila ovata using oxygen uptake in muscle slices. 2.2. Extracts of ganglia, kidney and liver in Ringer stimulate oxygen uptake in muscle slices. 3.3. Oxygen uptake is also stimulated by serotonin, some indole amines, some amines and adrenaline. 4.4. The factor in the liver is non-dialysable, heat stable, extractable in 95% acetone and partly soluble in chloroform. Evidence is given to suggest that the majority of the activity of the liver is not due to serotonin or tryptamine. The possibility of a steroid is raised. 5.5. An active factor is also present in the livers of two bilharzia vectors. The possible significance of this is discussed.

Summary

Various antimineralocorticoids resemble norbolethone (an anabolic agent) in that they protect the rat against digitoxin intoxication and inhibit the anesthesia produced by progesterone or pentobarbital.

▼ 1.1. Stability to frozen storage of the steroid-binding proteins of several species of fish for the principal androgens and corticosteroids was investigated. 2.2. The proteins that bind steroids were quite stable in all species during storage at -40^oC. 3.3. There was a loss in binding of steroids by cod and haddock plasma but not by salmon plasma stored at -17^oC. 4.4. The proteins that bind corticosteroids were less stable than those that bind androgens. 5.5. Saturation of plasma with nitrogen did not stabilize the steroid-binding proteins nor did storage in glass as contrasted with plastic bottles. 6.6. Since the stability of fish plasma proteins to frozen storage is not the same for all species, it is suggested that steroid-binding studies are best carried out on fresh plasma when the stability of the protein is not known.

▼ 

Summary

Electron microscopic studies revealed that spironolactone, given orally to rats, causes a marked proliferation of smooth-surfaced endoplasmic reticulum in hepatocytes. The characteristic fine structural alterations in the liver may represent the morphologic equivalent of stimulation or induction of drug metabolizing microsomal enzymes and may explain why spironolactone protects rats against the injurious effects of different compounds.

▼ The patterns of progesterone-4-^1^4C conversion by adrenal tissue and adenoma from a case of dexamethasone sensitive primary aldosteronism were compared in vitro. Morphologically the adrenal tissue appeared normal and the tumor was composed of cells resembling those of the zona fasciculata. Adrenal cortical tissue and the adenoma of the diseased gland converted labeled progesterone to deoxycorticosterone, 18-hydroxy-11 -deoxycorticosterone, aldosterone, 18-hydroxycorticosterone, 17α-hydroxyprogesterone, cortisol and cortisone. The biosynthesis of labeled C₁₉ steroids was not detected. Per unit of tissue weight the adenoma converted progesterone-4-^1^4C to aldosterone and 18-hydroxycorticosterone more efficiently than the adrenal tissue. Both types of tissue on timed incubation showed a stepwise utilization of labeled progesterone predominantly via 17-deoxysteroid pathway. The adenoma formed cortisol-^1^4C to a lesser extent that the adrenal cortical tissue. Biochemically the adenoma showed the presence of enzyme systems which are commonly found in the cells of the adrenal zona glomerulosa and fasciculata.

▼ 

Summary

A weak disturbance of the porphyrin metabolism was provoked in rats by intermittend feeding of 0.2% hexachlorobenzene. This disturbance is largely enhanced by injections of estradiol or combinations of estradiol with gestagen and androgen respectively. Injections of gestagen or androgen alone or feeding with ethanol showed only small changes in the porphyrin metabolism of this type of “latent porphyric rats”. The analogies of these results with observations in cases of humanporphyria cutanea tarda support the assumption, that the “latent HCB-porphyria of rats” is an appropriate model for screening drugs and other environmental factors for their porphyrogenic potency.

▼ 

The level of plasma free adrenocorticosteroids in three strains of normal mice were estimated. The steroid 11-deoxycortisol (Reichstein compound S) was found in relatively large quantities besides the secretion of corticosterone.The two steroids isolated by paper chromatography were identified by a number of other methods to establish and confirm their nature.The three strains of mice, all have both steroids: corticosterone and 11-deoxycortisol. The results show neither sex nor strain differences as regard to the quantity of corticosterone per 100 ml plasma.Corresponding differences in the ratio of 11-deoxycortisol to corticosterone (S/B ratio) were found between the strains.The importance of this 11-deoxycortisol and its possible physiological role has been discussed.

▼ Some of the main constituents of Marsdenia rostrata, originating from two localities, were isolated and identified. The sample from the Toonumbar State Forest in northern New South Wales contains the known alkaloid anabasine and two new steroidal ester alkaloids, rostratine and dihydrorostratine. They were identified as O-acetyl-O-nicotinoylsarcostin and O-acetyl-O-nicotinoyldihydrosarcostin. The sample from the South Coast of N.S.W. yielded the two new ester alkaloids and a number of neutral polyhydroxy pregnane aglycones, one of which has been identified as metaplexigenin, but there was no anabasine.

▼ The maternal pheromone in the postparturient female rat was shown to be under prolactin control. Ergocornine, a drug known to inhibit discharge of the tropin completely eliminated the pheromone, while prolactin replacement restored the pheromone. Removal of adrenal and ovarian hormones does not interfere with the emission of the attractant.

▼ 1.1. Biosynthesis of steroid hormones from radioactive progesterone, 17α-hydroxyprogesterone, androst-4-ene-3, 17-dione and testosterone by the adrenals of male and female Rhesus monkeys was studied. 2.2. On a comparative basis the adrenals from the female monkeys yielded a higher ratio of estrogens to androst-4-ene-3, 17-dione and/or testosterone among the biosynthetic products. 3.3. Probably due to the common embryologic origin, the sex chromatin constitution (XX, or XY) reflected is not only in gonadal but also in adreno-cortical enzyme activities. 4.4. Following gonadectomy, decreased sex difference in the biosynthetic activities of the adrenals was observed.

▼ The activity of the enzyme, 5-nucleotidase was measured, chemically and histochemically, in the aortas of male and female control rats, free of arterial disease, as well as male and female breeder rats which develop microscopic and grossly-visible arteriosclerosis of the aorta, respectively. Female rats manifested much greater aortic 5-nucleotidase activity than male rats. Very little difference could be detected between the aortic enzyme activity of male control rats and male breeder rats which had aortic microscopic lesions only. However, there was a significant and progressive increase in aortic 5-nucleotidase activity commensurate with and paralleling the progression of the severity of arteriosclerosis as well as its anatomical spread from the abdominal aortic segment to the arch and lastly, the thoracic aortic segment. The histochemical tests demonstrated that 5-nucleotidase activity first appears in the tunica intima coincidental with the appearance and accumulation of mucopolysaccharide. As the intimal mucopolysaccharide is converted into collagen the 5-nucleotidase activity disappears. In the media, 5-nucleotidase activity becomes diffusely and strongly positive in close proximity to the internal elastic membrane. As the medial degenerative changes become more exacerbated and calcific changes appear the 5-nucleotidase reaction becomes most intense. These chemical and histochemical observations are construed to be an indication of the hormonal effects of repeated breeding inducing medial smooth muscle cell changes in association with 5-nucleotidase activity to affect ground substance and connective tissue changes which favor sclerosis and calcification of the aortic wall of breeder rats.

▼ 

The effects of neonatal and adult administrations of gonadal hormones were investigated on the activity of regional brain choline acetylase (ChAc) and fighting behavior in the mouse. It was found that, generally, the hormonal treatments resulted in consistent increases in hypothalamic and hippocampal ChAc, and inconsistent changes in cortical ChAc. Increases in enzyme activity were not accompanied by similar increases in fighting. There was a lack of positive correlation between a particular gonadal hormone used, the increase in ChAc and fighting A number of hypotheses are proposed.

▼ 

The aortae of non-arteriosclerotic female virgin and arteriosclerotic female breeder rats were divided into arch, thoracic and abdominal segments.Measurements were made of protein nitrogen and the rate of C¹⁴O₂ release from aortic segments of normal and arteriosclerotic aortae.The earliest metabolic differences found between arteriosclerotic and non-arteriosclerotic aortae appeared first in the abdominal aortic segment.The progression of aberrant metabolism followed the anatomical progression of the arterial disease.The deranged metabolism found in the aortae of arteriosclerotic breeder rats is believed to be due to the metabolic demands of repeated reproductive activity.

▼ 

Summary

It appears that the sex hormones and corticosteroids interact in the final outcome of gluconeogenesis. The female rats pre-treated with estradiol lose their liver glycogen on fasting at a lower rate than the rats pre-treated with testosterone or olive oil. Upon injection of cortisol to fasting rats it was shown that estradiol pre-treatment enables rats to accumulate liver glycogen at a faster rate than the pre-treatment with testosterone propionate. Large doses of estradiol but not of testosterone provoke an increased accumulation of liver glycogen in fasting intact but not in fasting adrenalectomized rats.

▼ 

Summary

The granulosa and the luteal cells have been studied in the ovary of the adult laying hen by histochemistry, autoradiography, polarized light and electron microscopy. It is concluded that the granulosa cells are specialized for the synthesis of proteins, whereas the luteal cells mainly secrete steroids. These conclusions have been tested by examining the cells under three naturally-occurring physiological conditions. (a) In the discharged follicles, the granulosa cells exhibit degenerative changes, and the luteal cells show reduced reactions in the tests for steroids. (b) In the ovaries of old, off-lay hens, the granulosa cells resemble those of the laying hen; the luteal cells however, whilst still showing positive reactions for steroids, have undergone morphological changes, some of which suggest that the cells are atrophic. (c) Luteal are recognisable in embryonic ovaries as early as nine days of incubation. By fifteen days, these cells show strongly positive reactions in tests for steroids.

▼ Summary

The effects of calcium on cholesterol metabolism have been examined in 6 patients. The age of the subjects ranged from 61–73 years. Five of the patients were osteoporotic. The calcium was administered as organic salts (calcium glycerophosphate or calcium gluconogalactogluconate) and as dried skimmed milk.

The results show that increased calcium in the organic form caused increased excretion of faecal bile acids and faecal total fat. There was no change in faecal neutral steroid output; increased faecal cholesterol was compensated by decreased coprostanol excretion. When the calcium was given in the form of skimmed milk, faecal bile acids and faecal fat remained elevated. Faecal excretion of cholesterol continued to rise and was accompanied by the return of faecal coprostanol output almost to the basal level, resulting in increased total neutral steroid excretion.

The serum cholesterol and triglyceride levels showed little change from the basal levels during the calcium supplementation periods.

▼ 

Summary

Digitoxin, ouabain, digoxin and their derivatives dihydrodigitoxin, dihydro-ouabain, and dihydrodigoxin were investigated in regard to their effects on the Na+ and K+ transport in incubated cold stored guinea-pig erythrocytes.

The ion transport is inhibited by 50% in the following concentrations of the different glycosides: digitoxin 3.0 × 10⁻⁷ M, ouabain 1.0 × 10⁻⁶ M, digoxin 1.2 × 10⁻⁶ M.

The saturation of the lactone ring decreases the potency of all three glycosides by the same order of magnitude. The potencies of the dihydro-derivatives in relation to their parent compounds are: dihydro-digitoxin 1/22, dihydro-ouabain 1/34, and dihydro-digoxin 1/25.

▼ 

1. The incorporation of sodium acetate-1-¹⁴C into some classes of lipids inParacentrotus lividus, Echinus acutus andPsammechinus miliaris is investigated.2. It is demonstrated that these animals utilized the injected acetate for the biosynthesis of fatty acid and non-saponifiable lipids including squalene and 3-β-sterols.3. It is supposed that probably all echinoids are able to synthesize 3β-sterols.

▼ 1.1. The steroid content of the ovaries and fat bodies of female Triturus cristatus carnifex have been analysed during the breeding season. 2.2. Progesterone and androstenedione have been identified in the ovarian extract; the following steroids have been identified in the fat bodies: pregnenolone, progesterone, dehydroepiandrosterone, testosterone and estrone. 3.3. Incubations of acetone powder carried out separately with ovarian and fat body tissue using cholesterol-4-C^1^4 as the substrate yielded the following metabolites in the case of the ovary: progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone; and in the case of the fat bodies: pregnenolone, 17α-hydroxypregnenolone, 17α-hydroxprogesterone, and testosterone. 4.4. Incubations with either tissue using testosterone-4-C^1^4 as the substrate yielded 11-ketotestosterone, 11β-hydroxyandrostenedione, androstenedione and esterone. 5.5. These findings support the view that steroid hormones identified in the fat bodies could be produced in situ from cholesterol.

▼ Lysosomal enzyme content (acid and alkaline phosphatases, N-acetyl-β-glucosaminidase, β-glucuronidase) of perfusates from rat paws was determined at various time intervals after induction of nystatin and carrageenin inflammation. In nystatin-induced inflammation, there was a significant increase in the lysosomal enzyme content of the perfusates which paralleled development of oedema. Such a release is dependent on the availability of leucocytes, since in rats made leucopenic by methotrexate administration a significant correlation was observed between the number of blood leucocytes and the concentration of lysosomal enzymes in the perfusates obtained from inflamed paws. The release of lysosomal enzymes was inhibited in decreasing order of potency by dexamethasone, azapropazone, indomethacin, betamethasone (administered in doses roughly equipotent in inhibiting oedema development). Phenylbutazone, prednisolone and aspirin were completely inactive in this respect.

▼ 

Summary

The ultrastructure of the interstitial cells in the testis of Trichogaster leeri (Anabantoidei, Teleostei) is described. In these cells small mitochondria, containing only cristae, occur by the side of large mitochondria (up to 3 μ in diameter) which possess cristae as well as tubules. The tubules are oriented in parallel wavy bundles and may show a regular circular striation of their walls. Various stages of differentiation of these mitochondria are compared with mitochondria in steroid producing endocrine organs.

▼ 

Summary

In the zona reticularis of the rat adrenal cortex three types of cells are to be observed: light, dark, and very dark cells. A time study of the incorporation of cholesterol-3H into these elements has been made. The data obtained from autoradiographic study are discussed in relation to the hypothesis that the light cells are elements in active steroido-synthesis, the dark cells are resting elements, and the very dark cells are elements in degeneration.

▼ 

Summary

The fine structure of ovarian steroid-producing cells of the domestic fowl as seen after administration of steroids is described. Diaethylstilboestrol, estradiol and hydroxyprogesterone were given as intramuscular injections for a 28-days period. The main cytoplasmic changes of the steroid-producing cells were an increase in the number and the size of lipid droplets due to a possible expansion of the endoplasmic reticulum and a confluence of the smooth endoplasmic reticulum and the lipid droplets. The mitochondria became paler, markedly reduced in size and number, and contained less cristae. The Golgi apparatus became smaller and tended to disappear. The most prominent nuclear changes were irregular outline of the nuclear membrane, shrinkage of the nucleus, formation of pseudo-inclusions, decreased number of nuclear bodies with a tendency to vacuolization and small nucleoli. These alterations have never been demonstrated in ovarian steroid-producing cells before, and they are consistent with atrophic changes observed in steroid-producing cells in other organs. The present study substantiates the view that the thecal gland must be concerned with endocrine function. The possible functions of the different cell types of the thecal gland are discussed.