Seven cases of biopsy-proved juvenile nasopharyngeal angiofibroma are presented. All patients were males. Examination under anesthesia and tomography and angiography were very rewarding in determining the full extent of tumor. Selective carotid angiography revealed a characteristic early arterial phase with reticulated vessels, and a homogeneous blush continuing into the venous phase without early draining veins. The tumor has a strong predilection for young males. Chromosomal studies and estimation of <em>17</em>-<em>ketosteroids</em> in 4 patients were normal. None of the patients demonstrated sexual underdevelopment. All were treated by external radiotherapy with 3000 rads in 15 fractions in three weeks with good results. There were no undue side effects.

Incidentally diagnosed, clinically asymptomatic adrenal masses (incidentaloma) have become more and more common problem in everyday clinical practice. The prevalence of such tumors is 2.3% in autopsy series and 0.5-2% in computed tomography series. The aim of the study was a clinical analysis of patients with adrenal incidentaloma, hospitalized in the Department of Internal and Metabolic Diseases of the Medical University of Silesia.

METHODS

33 patients, including 25 females (75.7%) and 8 males (24.3%), were investigated. The mean age was 59.0 +/- 10.7 year (31-80) and the mean body mass index (BMI) was 29.6 +/- 5.9 kg/m2 (19.4-47).

RESULTS

16 patients (48.5%) were obese and 10 more patients (30.3%) were overweight. Hypertension was diagnosed in 25 patients (75.8%), diabetes or impaired glucose tolerance in 9 patients (27.3%) and hyperlipidemia in 20 patients (60.6%). Endocrine tests revealed: disturbed cortisol rhythm in 1 patient, uncertain result of the overnight dexamethasone suppression test in 4 patients, elevated urinary <em>17</em>-hydroxycorticosteroids excretion in 7 patients, elevated urinary <em>17</em>-<em>ketosteroids</em> excretion in 2 patients and increased urinary excretion ofvanillylmandelic acid in 2 patients. The tumor was located in the right adrenal gland in 13 patients (39.4%) and in the left adrenal gland in 16 patients (48.5%). 4 patients (12.1%) demonstrated bilateral adrenal masses. At least one of the tumor sizes was greater than 40 mm in 3 patients (9.1%).

CONCLUSIONS

Clinically asymptomatic adrenal tumors occurred more frequently in overweight or obese women, between 51-70 years old, with lipid disorders and hypertension.

The functional relationship between the microsomal cytochrome P450 and <em>17</em> beta-hydroxysteroid oxidoreductase (HSOR) enzymes involved in steroid metabolism was investigated in rat liver. In male and female rat hepatic microsomes the NADPH-dependent conversion of androstenedione (AD) to testosterone (T) was approx. 4-fold greater at 6 weeks of age than in 1 week old animals. In hepatic microsomes from 15 week old rats the activity of the HSOR pathway was greater in males than in females (1.51 compared to 0.80 nmol T formed/min/mg protein). However, oestradiol administration to intact adult male rats did not decrease HSOR activity. Thus, androgen is not essential for maintenance of HSOR enzymes. Instead, it is likely that irreversible androgen imprinting of the HSOR enzyme occurs during the prepubertal period. The in vitro characteristics of HSOR activity were also assessed. The Km for NADH-dependent reduction of AD to T was 9.2 microM and the Vmax was 3.0 nmol/min/mg protein but the NAD-mediated formation of AD from T did not follow Michaelis-Menton kinetics. pH markedly influenced HSOR-mediated AD/T interconversion with <em>17</em>-<em>ketosteroid</em> reduction facilitated at low pH, and <em>17</em> beta-hydroxysteroid dehydrogenation about 2-fold more efficient at pH 8.0 than at pH 5.5. Product steroid activation of HSOR activity was noted. <em>17</em> beta-Hydroxysteroids, including T and oestradiol, activated the rate of conversion of AD to T and <em>17</em>-<em>ketosteroids</em> such as oestrone and AD activated the NAD-dependent dehydrogenation of T. Activation was not observed at low steroid substrate concentrations so that it was not possible to analyse this phenomenon by a conventional kinetic approach.

The Authors examine possible connections between the schizophrenic syndrome and the hypothalamo-pituitary-gonadal system, assuming that hormonal impairments may correlate with the appearance and development of peculiar behavioral features. The hormonal status and the behavioral parameters have been examined before, during and after a psychopharmacological therapy, and a combination of a psychopharmacological-hormonal treatment. Data have been obtained in 12 male hebephrenic schizophrenics, aged 18-36 years, with onset of the disease between 12 months and 20 years before our experiments. The patients were treated for 30 days with Haloperidol (6 mg.i.m.p.d. to a total dose of 180 mg.) and then for 45 days with Haloperidol at the same dose in combination with Chorionic Gonadotrophin (5000 I.U.i.m. twice a week for a total dose of 60.000 I.U.). The following hormonal assays were performed: total urinary gonadotrophins, serum FSH and LH, total urinary <em>17</em> <em>ketosteroids</em>, total urinary estrogens, serum testosterone. The hormonal assays were performed twice prior to therapy, twice during the Haloperidol therapy (12th and 26th days) twice during the Haloperidol plus HCG therapy (20th and 40th day) and 1 month after the withdrawal of the therapy. The psychological-behavioral parameters were examined through the Wittenborn Rating Scale. The result obtained seem to reveal a stimulatory effect of the Haloperidol plus HCG therapy on the deficient hormonal status. Moreover, it is evident that a constant correlation exists between biochemical improvement and behavioral improvement, especially in regard to affectivity disorders, adjustment to reality, active behavior.

To investigate the effects of androgens on the fatty acid compositions of sebum wax esters, we examined sebum and urinary samples from 36 healthy individuals, aged from 3 to 59 years. The percentages of C16:1 straight chain components in wax esters were correlated positively with the urinary testosterone levels in both sexes, and with the urinary levels of etiocholanolone and total <em>17</em>-<em>ketosteroids</em> (<em>17</em>-KS) in females. These data suggest that more active sebaceous glands in lipid production excrete sebum with a higher proportion of C16:1 straight chain fatty acid, which is considered to be purely endogenous. It appears, therefore, that the proportion of C16:1 straight chain fatty acid in sebum wax esters may indicate the sebaceous gland activity in both sexes. In comparison of the amounts of various straight and terminally branched fatty acids in sebum with urinary androgen levels, the straight even fatty acids tended to change in a positive correlation with testosterone levels, in contrast to the changes of the iso even fatty acids in both sexes and to those of the iso odd fatty acids in males. The straight odd fatty acids showed a similar change to that of the straight even fatty acids in males, while in females, there was no significant correlation between the amounts of the fatty acids and testosterone levels. Anteiso fatty acids showed no notable change correlated with testosterone levels. This result suggests that the synthesis of iso or anteiso fatty acids may be controlled by complex factors and that there may be a unique source of anteiso fatty acids in human sebaceous glands.

OBJECTIVE

We attempted to test the hypothesis that distinct forms of the <em>17</em>-<em>ketosteroid</em> oxidoreductase exist in the human ovary and to compare its activity in stroma obtained from normally cycling women and from hyperandrogenic women.

METHODS

Human ovarian granulosa-luteal cell and stromal <em>17</em>-<em>ketosteroid</em> oxidoreductase were examined in cell incubations and subcellular homogenates.

RESULTS

In subcellular homogenates of granulosa-luteal cells <em>17</em>-<em>ketosteroid</em> oxidoreductase activity was greater in the cytosol fraction than in the membrane fraction. In contrast, in homogenates of both ovarian stroma and Leydig cells its activity was greater in the membrane fraction than in the cytosol fraction. At the substrate concentrations used estrone was a better substrate than androstenedione for the granulosa-luteal cell <em>17</em>-<em>ketosteroid</em> oxidoreductase. In contrast, androstenedione was a better substrate than estrone for that in ovarian stromal and Leydig cell membranes. In incubations of ovarian stroma from hyperandrogenic women, significantly more testosterone accumulated in the medium per milligram of tissue than in the medium of incubations of ovarian stroma from normally cycling women (142 +/- 48 vs 7.9 +/- 7.5 pg testosterone per milligram of tissue per 48 hours, mean +/- SD, p less than 0.05). The ratio of testosterone to androstenedione was significantly higher in the medium of incubations of ovarian stroma from hyperandrogenic women than in that from normally cycling women (0.61 vs 0.25, mean, p less than 0.05). The ratio of serum testosterone to androstenedione was significantly greater in hyperandrogenic women than in normally cycling control women (0.31 +/- 0.11 vs 0.20 +/- 0.03, mean +/- SD, p less than 0.05).

CONCLUSIONS

The localization (cytosol fraction) and substrate specificity (estrone) of the granulosa-luteal cell <em>17</em>-<em>ketosteroid</em> oxidoreductase enzyme resembles that seen in human placenta. The localization (membrane fraction) and substrate specificity (androstenedione) of the ovarian stromal <em>17</em>-<em>ketosteroid</em> oxidoreductase enzyme resembles that seen in Leydig cells. It may be one enzyme that exists in multiple forms or it may be two (or more) enzymes. In some hyperandrogenic women the ovarian stromal <em>17</em>-<em>ketosteroid</em> oxidoreductase may be more active than in normally cycling women, contributing to an abnormally increased testosterone production rate.

The present study was designed to assess the dose-dependent effects of ethanol on Leydig cells of adult albino rats of the Wistar strain. Ethanol was given orally through gastric intubation at three different dose levels (0.5, 1 and 3 g/kg body weight) twice daily as 25% (v/v) aqueous solution for 15 days. Ethanol treatment reduced body and testes weights. Serum testosterone registered a decrease while estradiol levels became elevated. Activities of the steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and <em>17</em>-<em>ketosteroid</em> reductase (<em>17</em>-KSR) decreased significantly. The glucose oxidative capacity of Leydig cells was impaired by ethanol treatment in a dose-dependent manner. Similarly, ethanol treatment caused significant reduction in LH receptors on the Leydig cell membrane at higher doses (1 and 3 g/kg) whereas no significant change was observed with the lower dose (0.5 g/kg) as compared to controls. The present findings suggest that the decrease in Leydig cellular LH receptors, glucose oxidation and the activities of 3beta-HSD and <em>17</em>-KSR are possible mechanisms by which ethanol treatment perturbs Leydig cell steroidogenesis.

Nine elderly men with prostatic carcinoma underwent treatment with a LHRH-agonist (Zoladex, ICI) for 3-6 months. At the end of the treatment period the patients underwent subcapsular orchidectomy. Testicular tissue was incubated with different tritiated testosterone precursors. Conversion mediated by several testicular steroidogenic enzymes was compared between Zoladex-treated patients and nineteen non-treated patients who underwent orchidectomy because of prostatic carcinoma. Serum concentrations of LH, FSH and testosterone were determined before and during treatment in the treated patients. The LHRH agonist treatment induced significantly decreased conversion mediated by the enzymes 3 beta-hydroxysteroid dehydrogenase, <em>17</em> alpha-hydroxylase and C<em>17</em>-20 lyase. Conversion mediated by <em>17</em> beta-<em>ketosteroid</em> reductase was also decreased although not as dramatically as the other enzymes, while conversion mediated by 20 alpha-dehydrogenase was increased. Serum concentrations of testosterone decreased to castration levels. Serum gonadotrophins decreased but remained within normal levels suggesting that "desensitization" at the pituitary level was not the only mechanism of action of the LHRH-agonist.

The unexpected arrival of an infant with ambiguous genitalia is stressful for both physicians and parents. Careful assessment of the external genital structures and the overall infant directs the immediate management. Investigations include evaluation of glucose, electrolytes, chromosomes, and <em>17</em>-<em>ketosteroids</em> as well as ultrasound and evaluation of the urinary tract as appropriate. The review of family and pregnancy history addresses concerns regarding medications or previously affected infants. The most efficient method of evaluating such an infant is by a team approach, with each team member contributing expertise and one communicating with the family and the family physician. Unnecessary overlap of investigations can be avoided as well as rash decisions as to sex of rearing. Counseling the family provides support during the stressful first days until decisions can be made about information regarding the diagnosis and prognosis of the infant, recurrence risk figures for subsequent pregnancies or other family members, and whether prenatal diagnosis might be appropriate. The family can be helped to move through the ordeal with their child and develop trust in the team members.

A 4-year-old girl had abdominal distention, muscular weakness, renal tubular dysfunction, and hypertension associated with hypokalemic metabolic alkalosis. There were no clinical symptoms of cortisol deficiency, but there was excessive deoxycorticosterone and cortisocsterone production. Basal plasma aldosterone levels were undetectable; however, adrenocorticotropic hormone (ACTH) stimulation brought plasma aldosterone levels up to normal. The urinary pregnanediol, tetrahydro-deoxycorticosterone (THDOC), and tetrahydrocorticosterone (THB) concentrations were elevated. Stimulation of ACTH failed to increase urinary <em>17</em>-<em>ketosteroid</em>, <em>17</em>-hydroxycorticosteroid, or plasma cortisol levels significantly, while urinary THDOC, THB, and plasma corticosterone concentrations were further elevated. The elevated plasma corticosteroid intermediates were suppressed by dexamethasone administration. When physiologic doses of dexamethasone were administered, the hypertension, electrolyte imbalance, and abnormal corticosteroid secretion were all corrected. The studies indicated a partial <em>17</em>alpha-hydroxylase defect in this patient.

We found an association between low levels of <em>17</em>-<em>Ketosteroid</em> Sulfates (<em>17</em>-KS-S) in subjects under psychosocial stress. Stress associated with overwork and lack of sleep resulted in decreased levels of <em>17</em>-KS-S and an increase in <em>17</em>-Hydroxycorticosteroids (<em>17</em>-OHCS) levels. Alleviation of stress condition was associated with a restoration of the ratio of <em>17</em>-KS-S/<em>17</em>-OHCS resulting from a slow increase in <em>17</em>-KS-S and a decrease in <em>17</em>-OHCS. In subjects with severe mental stress the ratio of <em>17</em>-KS-S/<em>17</em>-OHCS showed markedly reduced values with a transient marked increase in <em>17</em>-OHCS. There was a decrease in the levels of <em>17</em>-KS-S in depressives, which was more pronounced during severe depression. There was no significant difference in <em>17</em>-OHCS levels. In a cohort experiencing bereavement, there was a reduction in the levels of <em>17</em>-KS-S, which remained low for about 50 days. With time, the level of <em>17</em>-KS-S returned to the basal level established prior to spousal death. In this case, there was no significant change in the levels of <em>17</em>-OHCS. Persistent severe stress over several months in a physician, led to a Herpes Zoster outbreak and Arrhythmia, resulting in hospital admission. The levels of <em>17</em>-KS-S gradually decreased over this time reaching 1/3 of the normal baseline value, while <em>17</em>-OHCS levels remained within normal ranges. These results suggest that measurement of <em>17</em>-KS-S is indispensable for current research on psychosocial stress.

The biosynthesis of non-aromatic 19-norsteroids has been studied using primary cultures of porcine granulosa cells. Formation of 5(10)-estrene-3 beta,<em>17</em> beta-diol, a novel 19-norsteroid, from androstenedione and 19-hydroxyandrostenedione by porcine granulosa cells is reported for the first time. The structure was deduced from (i) comparison of its elution times on C18 reverse phase HPLC with authentic 5(10)-estrene-3 beta,<em>17</em> beta-diol (ii) identification with 5(10)-estrene-3 beta,<em>17</em> beta-diol-diacetate after acetylation (iii) oxidation/acid catalysed isomerization to 19-norandrostenedione. Serum or serum plus FSH significantly stimulated (seven fold increase) formation of 5(10)-estrene-3 beta,<em>17</em> beta-diol from androstenedione and 19-hydroxyandrostenedione. Formation of 5(10)-estrene-3 beta,<em>17</em> beta-diol from both substrates was significantly (p less than 0.01) reduced by the aromatase inhibitors 4-hydroxyandrostenedione (15 microM) and aminoglutethimide phosphate (10(-4)M). These results suggest that 5(10)-estrene-3 beta,<em>17</em> beta-diol (and 19-norandrostenedione) may be formed by enzymes similar to the aromatase complex required for estradiol-<em>17</em> beta biosynthesis. 5(10)-Estrene-3 beta,<em>17</em> beta-diol is converted by granulosa cells to four metabolites. 19-Norandrostenedione was identified by crystallization to constant specific activity; 19-nortestosterone is a minor product. Production of 19-norandrostenedione and 19-nortestosterone indicates that granulosa cells possess the enzymes necessary for the transformation of 5(10)-estrene-3 beta,<em>17</em> beta-diol and other 3-hydroxy-5(10)-estrenes to 19-nor-4-ene-3-<em>ketosteroids</em>. The formation of 5(10)-estrene-3 beta,<em>17</em> beta-diol and 19-norandrostenedione as substantial metabolites of androstenedione suggest a physiological role for these 19-norsteroids in ovarian follicular development.

Hydroxysteroid (<em>17</em>β)-dehydrogenase type 1 (HSD<em>17</em>B1) catalyzes the conversion of low active <em>17</em>-<em>ketosteroids</em>, androstenedione (A-dione) and estrone (E1) to highly active <em>17</em>-hydroxysteroids, testosterone (T) and E2, respectively. In this study, the importance of HSD<em>17</em>B1 in ovarian estrogen production was determined using Hsd<em>17</em>b1 knockout (HSD<em>17</em>B1KO) mice. In these mice, the ovarian HSD<em>17</em>B enzyme activity was markedly reduced, indicating a central role of HSD<em>17</em>B1 in ovarian physiology. The lack of Hsd<em>17</em>b activity resulted in increased ovarian E1:E2 and A-dione:T ratios, but we also observed reduced progesterone concentration in HSD<em>17</em>B1KO ovaries. Accordingly with the altered steroid production, altered expression of Star, Cyp11a1, Lhcgr, Hsd<em>17</em>b7, and especially Cyp<em>17</em>a1 was observed. The ovaries of HSD<em>17</em>B1KO mice presented with all stages of folliculogenesis, while the corpus luteum structure was less defined and number reduced. Surprisingly, bundles of large granular cells of unknown origin appeared in the stroma of the KO ovaries. The HSD<em>17</em>B1KO mice presented with severe subfertility and failed to initiate pseudopregnancy. However, the HSD<em>17</em>B1KO females presented with normal estrous cycle defined by vaginal smears and normal puberty appearance. This study indicates that HSD<em>17</em>B1 is a key enzyme in ovarian steroidogenesis and has a novel function in initiation and stabilization of pregnancy.

The authors report on a case where complete blockade of 21-hydroxylase was discovered in a 40-year-old subject. They emphasize the usefulness of urinary <em>17</em>-<em>ketosteroid</em> and <em>17</em>-OH progesterone assays in the diagnosis of pseudo-hermaphroditism. In contrast to major hyperandrogenism, the HY antigen test is negative, since the percentage of fluorescent lymphocytes is even lower than in the normal female population.

We measured both urinary <em>17</em>-hydroxycorticosteroids(<em>17</em>-OHCS) and <em>17</em>-<em>ketosteroid</em> sulfates(<em>17</em>-KS-S) in normal children and in children with some diseases to evaluate adaptation to stress in children. <em>17</em>-OHCS and <em>17</em>-KS-S values were measured in morning urine from 60 normal children(3-18 years old) and 24 children with atopic dermatitis or renal disease. In normal children, the <em>17</em>-OHCS/creatinine showed no difference by age, but both <em>17</em>-KS-S/creatinine and <em>17</em>-KS-S/<em>17</em>-OHCS showed significant positive correlation with age. No sex differences were significant. In children with atopic dermatitis or with renal disease treated with cyclosporine A, <em>17</em>-OHCS/creatinine was significantly higher and the <em>17</em>-KS-S/<em>17</em>-OHCS ratio was significantly lower than in age-matched controls. These values returned to normal as the conditions improved or as treatment ended. In patients who underwent renal biopsy, both <em>17</em>-OHCS/creatinine and <em>17</em>-KS-S/creatinine values were significantly higher after biopsy than before because of the stress caused by pain and complete bed rest. Measurement of urinary <em>17</em>-OHCS and <em>17</em>-KS-S in children can be useful for evaluation of adaptation to stress as well as in adults.

Myotonic dystrophy is frequently associated with testicular atrophy. Since androgens may play a role in the maintenance of muscle mass, we have studied the levels of plasma testosterone and gonadotropins and of urinary <em>17</em>-<em>ketosteroids</em> in 22 men with myotonic dystrophy, 36 normal men, and 16 men (control group) with muscle wasting. Results were correlated with muscle mass as estimated by creatinine excretion and total body potassium. Patients with myotonic dystrophy had significantly lower testosterone and higher gonadotropin levels than normal, and these changes were progressive in longitudinal studies. Testosterone levels were also lower than normal in disease control subjects. There was no correlation between low testosterone levels and diminished muscle mass in either myotonic dystrophy or disease control patients. The low plasma concentration of testosterone in men with myotonic dystrophy and other neuromuscular diseases does not appear to be directly related to their muscle wasting. This study does not exclude the possibility that an alteration in testosterone receptor or tissue effects may contribute to a loss of muscle tissue.

1. The aim of the present study was to investigate the effects of a short (1 day) fast by testing biohumoral variables associated with the human circadian rhythm. 2. Fifteen clinically healthy male volunteers (32 +/- 8 years old) participated in the study. Subjects were fed a control diet for 7 days. The last day was a control day and the following 8th day was the fasting day. Each subject was asked to collect urine seven times over a 24 h period. Chemical and hormonal variables were measured in each fractionated urine specimen. The time- qualified urinary excretion rates were biometrically analysed using conventional and chronobiological methods. 3. During fasting, significant incremental changes were detected in the urinary excretion rates of potassium, aldosterone, <em>17</em>-hydroxycorticosteroids and adrenaline and significant decremental changes were detected in the excretion rates of sodium, chloride, creatinine, urea nitrogen, uric acid, <em>17</em>-<em>ketosteroids</em>, noradrenaline and dopamine. The circadian rhythmicity of the variables was well preserved and remained almost stable throughout the fasting phase. 4. Fasting affected the mean oscillatory levels and oscillatory amplitudes of variables, suggesting that nutrients may have played roles as tonic and phasic modulators on the mechanisms that physiologically regulate ircadian rhythmicity.