Testes of 28- and 70-day-old golden hamsters were separated into seminiferus tubules and interstitial tissue by wet dissection. Homogenates of the tissues and subcellular fractions were incubated with [14C]androstenedione, and NADPH and enzyme activity (nanomoles per 100 mg protein/h) was estimated. In immature testes, the 5 beta-reductase activity was largely confined to the seminiferous tubules, while 5 alpha-reductase was localized in the interstitial tissue. The activity of <em>17</em> beta-ol-dehydrogenase was found to be equally distributed between tubules and interstitial tissue. Although the activities of 5 beta- and 5 alpha-reductases were approximately 10 times greater in immature than adult testes, the <em>17</em> beta-ol-dehydrogenase activity in adult testes was approximately 10 times that in immature testes. In the immature testes, most 5 alpha-reductase and <em>17</em> beta-ol-dehydrogenase were localized in microsomes, whereas 5 beta-reductase was wholly localized in cytosol. These results indicates that 5 beta-reduction of delta 4-3-<em>ketosteroids</em> takes place largely in cytosol of tubular cells, while 5 alpha-reduction occurs in microsomes of interstitial cells in the testis of the immature golden hamster.

The potent gonadal steroids testosterone and estradiol are synthesized from the biologically weak precursors, androstenedione and estrone, by enzymatic reduction of the ketone group at carbon-<em>17</em> of the steroid nucleus (<em>17</em>-<em>ketosteroid</em> reductase). To test the hypothesis that Leydig and granulosa cells may contain a distinct <em>17</em>-<em>ketosteroid</em> reductase enzyme, the subcellular localization and the substrate specificity of the enzyme was examined in each cell type. In Leydig cells, the <em>17</em>-<em>ketosteroid</em> reductase activity was concentrated in the microsomal fraction of the cell. In granulosa cells, the <em>17</em>-<em>ketosteroid</em> reductase activity was concentrated in the cytosolic fraction of the cell. In Leydig cell microsomes, the apparent Michaelis-Menten constant for the conversion of androstenedione to testosterone was 0.41 mumol/L and for the conversion of estrone to estradiol it was 12 mumol/L. In granulosa cell cytosol, the apparent Michaelis-Menten constant for the conversion of estrone to estradiol was 1.1 mumol/L and for the conversion of androstenedione to testosterone it was 15 mumol/L. These results demonstrate that rat Leydig and granulosa cells each contain a <em>17</em>-<em>ketosteroid</em> reductase enzyme with unique subcellular localization and substrate specificity.

We report six women with severe acne lesions associated with taking amineptine, a tricyclic antidepressant. The lesions appeared after self-administration of high doses of the drug over long periods of time. They mainly occurred on the face, back, and thorax, but were also found on the extremities and in the perineal region. In five of the six cases, severity of cutaneous lesions appeared to be correlated with degree of overdose. The sixth patient never admitted having taken amineptine. Most of the patients had been unsuccessfully treated with isotretinoin for 18 months. In all six cases, chromatography of urinary <em>17</em>-<em>ketosteroids</em> showed abnormal peaks and retention times which were different from those usually found for known steroids. In addition, the areas under these peaks were found to be a function of the degree of intoxication and of the clinical severity of the lesions. Mass spectrometry was used to qualitatively study urinary amineptine metabolites, disclosing compounds normally found only in trace amounts, as well as certain others heretofore not described in man. In two of the three patients who stopped taking amineptine, cutaneous lesions subsequently diminished, totally disappearing in the least severe case.

The 50% ethanolic extract of the root bark of C. odorata administered orally at the dose of 1g/kg body weight/day for 60 days resulted in decreased epididymal sperm motility and sperm count in male albino rats. Morphological abnormalities were also observed in the sperms. The testicular glycogen, the activities of 3beta hydroxy steroid dehydrogenase, glucose 6-phosphate dehydrogenase, malic enzyme, sorbitol dehydrogenase in seminal vesicle, fructose in seminal plasma and serum testosterone were significantly decreased in treated group. While testicular cholesterol level, the concentration of the fecal bile acids, urinary excretion of <em>17</em> <em>ketosteroids</em>, the activities of <em>17</em>beta hydroxy steroid dehydrogenase, epididymal lactate dehydrogenase and that of testicular HMG CoA reductase were increased in treated group when compared to control. The results suggest that the ethanolic extract of C. odorata possesses the spermatotoxic effects in male albino rats.

Adrenocortical carcinomas are very rare tumors. The diagnosis and therapeutic results in 5 female patients are reported. In 4 cases the tumor displayed biochemical and clinical features of Cushing's syndrome, while one was an adrenocortical carcinoma with hypersecretion of aldosterone only. The mean age was 53.6 +/- 8.2 years. In all four cases with Cushing's syndrome the diagnosis was established by measurement of urinary free cortisol extraction rates and excretion rates of <em>17</em>-ketogenic steroids (mean <em>17</em>94.5 +/- 1968 micrograms/24 h for free cortisol and 50.5 +/- 24.9 mg/24 h for <em>17</em>-ketogenic steroids), while the excretion of <em>17</em>-OH-steroids was in the normal range in one case with hypercortisolism. The patient with mineralocorticoid excess showed markedly elevated plasma aldosterone levels (840 pg/ml) and undetectable plasma renin activity (less than 0.2 ng/ml/3 h), but normal urinary excretion rates of <em>17</em>-hydroxy- and <em>17</em>-<em>ketosteroids</em>. The adrenal lesions were localized by intravenous pyelography or sonography and by angiographic procedures, while radioscanning by 131I-cholesterol showed no uptake of activity. Unilateral adrenalectomy was performed in four cases. After appearance of hormonally active metastases o,p'DDD was administered as an antitumor agent in 3 patients. Two of these patients died 10 and 25 months after surgery. One patient with multiple lung metastases is still alive, with a postoperative course of more than 80 months.

The effects of estrogens on the growth and enzyme activities for androgen synthesis in a mouse Leydig cell tumor line (T 124958-R) were studied. The s.c. implantation of a diethylstilbestrol pellet resulted in a marked enhancement of the tumor growth. 5 alpha-Reductase activity (nmol/g/h) in tumors rapidly grown in the presence of diethylstilbestrol pellet was 4 times higher than that in tumors slowly grown in the absence of diethylstilbestrol, whereas an inverse relation was found for <em>17</em> beta-hydroxysteroid oxidoreductase activity. <em>17</em>-Hydroxylase activities were similar in both tumors. The major C21- and C19-steroids formed from progesterone by the tumors grown in the presence of estrogen were 5 alpha-steroids such as 3 alpha- or 3 beta-hydroxy-5 alpha-pregnan-20-one, 3 alpha, <em>17</em>-dihydroxy-5 alpha-pregnan-20-one, androsterone, and 5 alpha-androstane-3 alpha, <em>17</em> beta-diol, whereas the major steroids formed by the tumors in the absence of estrogen were 4-ene-3-<em>ketosteroids</em> such as 20 alpha-hydroxy-4-pregnen-3-one, <em>17</em>-hydroxy-4-pregnene-3,20-dione, and testosterone. Furthermore, 10(-8) M of <em>17</em> beta-estradiol added in serum-free medium for 10 days significantly enhanced 5 alpha-reductase activities per 10(6) cells but significantly inhibited <em>17</em> beta-hydroxysteroid oxidoreductase activity in primary cell culture. These results indicate that estrogens stimulate the growth of T 124958-R in vivo and that estrogens may directly enhance 5 alpha-reductase activity but inhibit <em>17</em> beta-hydroxysteroid oxidoreductase activity in T 124958-R cells.

Granulosa and theca cell tumors are rather common gonadal stromal tumors. A postmenopausal patient with a granulosa cell tumor, who complained chiefly of breast tenderness and enlarging, abdomen, is presented. Preoperative and postoperative studies including serum estrone, estradiol, prolactin, FSH, and LH,as well as urinary estrogens, <em>17</em>-<em>ketosteroids</em>, and <em>17</em>-hydroxysteroids are reported. A plan of treatment and followup is suggested. It is recommended that survival data on patients with such slow-growing tumors be adjusted to reflect the true incidence of death from the specific tumor in question.

The conversion of [3H]-androstenedione to testosterone regulated by the enzyme <em>17</em> beta-<em>ketosteroid</em> reductase and the conversion of [3H]-progesterone to <em>17</em> alpha-hydroxyprogesterone and onwards along the delta 4 metabolic pathway was studied in vitro in human testicular tissue from 32 males (2 fetuses, 25 adult, infertile men and 5 elderly men with prostatic carcinoma). Additionally, two prepubertal boys were studied with respect to the conversion of [3H]-androstenedione to testosterone in vitro, whereas another seven boys were studied with reference to the conversion of [3H]-progesterone in vitro. It appeared, that in all cases, the conversion of androstenedione to testosterone was larger than the conversion of progesterone to <em>17</em> alpha-hydroxyprogesterone by way of the <em>17</em> alpha-hydroxylase and onwards along the delta 4 metabolic pathway. It is thus concluded that the <em>17</em> beta <em>ketosteroid</em> reductase is not a rate-limiting enzyme along the delta 4 metabolic pathway. No case of deficient <em>17</em> beta-<em>ketosteroid</em> reductase was found among the 25 infertile patients studied.

Estrogen action in the target cells is dependent on estrogen receptor activity and intracellular estrogen concentration, which, in turn, is affected by the serum concentration and local metabolism in these cells. During the reproductive years the main source of estrogens is the ovarian follicles, but in postmenopausal women most of the estrogens are formed in peripheral tissues. <em>17</em>Beta-hydroxysteroid dehydrogenases (<em>17</em>HSDs) catalyze the reaction between <em>17</em>beta-hydroxysteroids and <em>17</em>-<em>ketosteroids</em>, and several distinct <em>17</em>HSD isoenzymes have been characterized. <em>17</em>HSD type 1 catalyzes the reaction from low-activity estrone to high-activity estradiol. The type 2 enzyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. <em>17</em>HSD type 1 is expressed both in steroidogenic tissues and in the target tissues of steroid action, such as normal and malignant breast tissue, where it may be responsible for maintaining the high intracellular estradiol concentration seen in breast cancer specimens. Therefore, <em>17</em>HSD type 1 inhibitors may be useful in the treatment and/or prevention of estrogen-dependent malignancies, such as breast cancer. This article deals mainly with <em>17</em>HSD types 1 and 2 and their role in estrogen action in breast tissue.

Serum testosterone, follicle-stimulating hormone, luteinising hormone, and dihydro-epiandrosterone concentrations rose significantly in seven men studied during recovery from a severe exacerbation of chronic obstructive airways disease. Urinary <em>17</em>-<em>ketosteroids</em> also rose significantly though serum androstenedione and prolactin concentrations did not. Our findings suggest that hypoxia in this condition suppresses the hypothalamus or pituitary or both and that such suppression is reversible. In view of previous reports of increase in total body potassium and intracellular water with recovery from cor pulmonale, we also carried out metabolic studies on our patients. Low body potassium concentrations in cor pulmonale fell further with recovery, in part reflecting a fall in lean body tissue. Intracellular water appeared to increase on recovery despite a fall in other lean body mass indices (the simplest and most reliable being skinfold thickness). We suspect this result to be spurious and due to problems with equilibration in isotope dilution. Alternatively it may reflect waterlogging of cells. A false figure for intracellular water could be responsible for an unexpectedly low estimated intracellular potassium concentration on recovery. Our results cast doubt on isotope dilution methods for measuring body water compartments in disease states likely to cause changes in cell permeability.

Zr-containing MOF-808 is a very promising heterogeneous catalyst for the selective reduction of <em>ketosteroids</em> to the corresponding hydroxysteroids through a Meerwein-Ponndorf-Verley (MPV) reaction. Interestingly, the process leads to the diasteroselective synthesis of elusive <em>17</em>α-hydroxy derivatives in one step, while most chemical and biological transformations produce the <em>17</em>β-OH compounds, or they require several additional steps to convert <em>17</em>β-OH into <em>17</em>α-OH by inverting the configuration of the <em>17</em> center. Moreover, MOF-808 is found to be stable and reusable, and it is also chemoselective (only keto groups are reduced, even in the presence of other reducible groups such as C=C bonds) and regioselective (in 3,<em>17</em>-di<em>ketosteroids</em> only the keto group in position <em>17</em> is reduced, while the 3-keto group remains almost intact). Kinetic rate constant and thermodynamic parameters of estrone reduction to estradiol have been obtained by a detailed temperature-dependent kinetic analysis. The results evidence a major contribution of the entropic term, thus suggesting that the diastereoselectivity of the process is controlled by the confinement of the reaction inside the MOF cavities, where the Zr 4+ active sites are located.

Keywords: MOF-808; Meerwein-Ponndorf-Verley; heterogeneous catalysis; metal-organic frameworks; steroids.

The phytoecdysteroids (PEs) comprise a large group of biologically-active plant steroids, which have structures similar to those of insect-molting hormones. PEs are distributed in plants as secondary metabolites that offer protection against phytophagus (plant-eating) insects. When insects consume the plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die. Chemically, ecdysteroids are a group of polyhydroxylated <em>ketosteroids</em> that are structurally similar to androgens. The carbon skeleton of ecdysteroids is termed as cyclopentanoperhydro-phenanthrene with a <i>β</i>-side chain at carbon-<em>17</em>. The essential characteristics of ecdysteroids are a <i>cis</i>-(5<i>β</i>-H) junction of rings A and B, a 7-en-6-one chromophore, and a <i>trans</i>-(14<i>α</i>-OH) junction of rings C and D. Plants only synthesize PEs from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor; the most common PE is 20-hydroxyecdysone. So far, over 400 PEs have been identified and reported, and a compilation of 166 PEs originating from 1998 has been previously reviewed. In the present review, we have summarized 212 new PEs reported between 1999 and 2019. We have also critically analyzed the biological, pharmacological, and medicinal properties of PEs to understand the full impact of these phytoconstituents in health and disease.

Keywords: Anti-inflammatory; Anticancer activity; Antidiabetic; Antimicrobial; Antioxidant; Phytoecdysteroids; Secondary metabolites.

Serum concentrations of <em>17</em>-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, testosterone, and androstenedione and 24-hour excretion of <em>17</em>-<em>ketosteroids</em> and pregnanetriol were measured serially in 18 children with congenital adrenal hyperplasia (21-hydroxylase deficiency) during a two-year period. Correlations were sought between results of measurements of these steroids and clinical progress assessed by physical examination and skeletal maturity to determine if measurement of concentration of these substances at a single point in time could be used to gauge the dose of corticosteroids for optimum treatment. We found that these measurements of steroids were generally not useful indicators of optimum control of the disease. Repeated careful clinical examination and assessment of changes in growth velocity and skeletal maturation seem to be the best criteria on which to base dosage of corticosteroids used for therapy.