Plasma levels of C19 steroid glucuronides in pre-menopausal women with non-classical congenital adrenal hyperplasia.

Recent reports have thrown doubt on the role of measurements of plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG) as a marker of peripheral androgen metabolism in women with polycystic ovarian syndrome and idiopathic hirsutism. It has been suggested that a plasma profile of C19 steroid glucuronides may be more informative. While preliminary data indicates that both 3 alpha-diolG and androsterone G (ADTG) may arise from adrenal steroid precursors, there have been no reports of C19 steroid glucuronides in women with non-classical, or late-onset congenital adrenal hyperplasia (NC-CAH), who constitute a significant proportion of the hirsute female population. We therefore measured plasma levels of 3 alpha-diolG, ADTG and dihydrotestosterone G (DHTG) before and following a standard Cortrosyn test in 15 symptomatic and 3 asymptomatic NC-CAH patients, 5 heterozygote carriers for 21-hydroxylase deficiency (NCHETS) and 18 normal women. The effects of chronic glucocorticoid (GCR) therapy (greater than 3 months) on the C19 steroid glucuronide profile in the symptomatic patients was also investigated. Baseline plasma levels of all 3 glucuronides were significantly (P less than 0.001) higher in symptomatic patients compared with either normals or NCHETS. However, the order of discrimination was ADTG greater than 3 alpha-diolG greater than DHTG. There were no significant differences between steroid glucuronide levels for NCHET and normal women and the C19 steroid glucuronide concentrations for the asymptomatic NC-CAH patients were greater than 2 SD above the normal means. Moderate clinical improvement was observed in all patients receiving oral GCR therapy and was accompanied by approx. 80% suppression of the plasma levels of all 3 C19 steroid glucuronides. This contrasts with a mean suppression of androstenedione of only 50%. However, plasma levels of the C19 steroid glucuronides were not significantly increased in response to a short ACTH stimulation test. This may be explained by the fact that the androgen glucuronides are thought to be peripherally formed metabolites derived from unconjugated glandular secreted androgen precursors and thus their synthesis at 60 min following adrenal stimulation may lag substantially behind that of their respective precursors. There were significant linear correlations between the levels of all 3 glucuronides, but neither correlated with Ferriman-Gallway scores, body mass index or 17-hydroxyprogesterone levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Testicular and blood steroid levels in aged men

In this study, we have evaluated the hypophyso-gonadal axis in three groups of men aged 60-69, 70-79 and 80-91 years by measuring the intratesticular concentrations of several steroids (pregnenolone, progesterone, DHEA, DHEA-S, testosterone, estradiol) and serum levels of FSH, LH, testosterone, estradiol and sex hormone binding globulin (SHBG). The histological examination of testes revealed normal spermatogenesis in all examined samples. No significant changes in serum hormone and SHBG concentrations as well as in testicular steroid contents among the three groups of patients were found. However, the mean serum SHBG level was three times higher in the oldest men than in other groups and a positive correlation between patient's age and serum SHBG was observed. Therefore, the bioavailability of estradiol in the oldest men was likely diminished. Consequently, the hormonal status in aged men is rather unchanged but great variations observed between patients imply special cautious when the SHBG and estradiol levels are concerned.     

Omental and subcutaneous adipose tissue steroid levels in obese men

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.     

The radioimmunoassay of steroid glucuronides. The oestrogen C-3 glucuronides as haptens.

Antisera were prepared against three related oestrogen ring-A glucuronides, oestrone 3-glucuronide, oestradiol 3-glucuronide and oestriol 3-glucuronide. The corresponding 6,7-3H-labelled conjugates were synthesized as radioligands and the cross-reactions of the antisera against ring-A oestrogen glucuronides and other steroid conjugates were examined. The specificity of the antiserum against oestriol 3-glucuronide was compared with that raised against oestriol 16alpha-glucuronide, and the measurement of the former conjugate in late-pregnancy urine is discussed.     

Plasma and urine levels of electrolytes, urea and steroid hormones involved in osmoregulation of cetaceans

Cetaceans are well adapted to their hyperosmotic environment by properly developed osmoregulatory ability. A question here is how they regulate water and mineral balances in marine habitats. In the present study, we determined blood and urine levels of various chemicals involved in osmoregulation, compared them with those in artiodactyls, and characterized the values in the whales. Blood and urine samples obtained from baleen whales of common minke (Balaenoptera acutorostrata), sei (B. borealis), and Bryde's whales (B. brydei), and toothed whales of sperm whales (Physeter macrocephalus) were analyzed for osmolality, major electrolytes, urea, steroid hormones and glucose. The urine osmolality and Na(+) concentrations in the cetaceans were much higher than those in the cattle. Furthermore, the cetaceans had 5 to 11-fold urea in plasma than the cattle, and 2 to 4-fold urea in urine. There were no significant difference in the plasma concentrations of corticosteroids between the cetaceans and the cattle. The present results indicate that the osmoregulatory parameters seem to be not affected by the reproductive stage and sex steroid hormones. The concentrations of urea in plasma and urine of the baleen whales were higher than those of the sperm whales, indicating a possibility that their osmoregulatory mechanisms may be correlated to their feeding habits. The present results suggest that cetaceans have unique osmoregulatory mechanisms by which they excrete strongly hypertonic urine to maintain fluid homeostasis in marine habitats.     

Plasma obestatin levels in men with chronic atrophic gastritis

Obestatin is a recently discovered active peptide isolated from the stomach. The purpose of the present study was to investigate the modification of plasma obestatin levels in men with chronic atrophic gastritis. Men older than 65 years undergoing upper gastrointestinal endoscopy were included. All patients with chronic atrophic gastritis underwent multiple biopsies. Fasting plasma obestatin and ghrelin levels were examined in 50 men with chronic atrophic gastritis and 50 healthy men. Plasma obestatin levels were significantly lower in patients with chronic atrophic gastritis than in healthy subjects. Plasma ghrelin levels and ghrelin to obestatin ratio was decreased in men with chronic atrophic gastritis. There was a significant relationship between atrophy and decreased obestatin. A negative correlation was found between circulating obestatin levels and body mass index (BMI) in healthy subjects, but not in patients with chronic atrophic gastritis. The data indicated that chronic atrophic gastritis influenced plasma obestatin levels as well as ghrelin to obestatin ratio in elderly men.     

Plasma and salivary steroid hormone responses of men to high-intensity cycling and resistance exercise

Hormonal responses to exercise could be used as a marker of overreaching. A short exercise protocol that induces robust hormonal elevations in a normal trained state should be able to highlight hormonal changes during overreaching. This study compared plasma and salivary cortisol and testosterone responses to 4 exercise trials; these were (a) continuous cycle to fatigue at 75% peak power output (Wmax) (FAT); (b) 30-minute cycle alternating 1-minute 60% and 1 minute 90% Wmax (60/90); (c) 30-minute cycle alternating 1-minute 55% and 4-minute 80% Wmax (55/80); and (d) Squatting 8 sets of 10 repetitions at 10 repetition maximum (RESIST). Blood and saliva samples were collected pre-exercise and at 0, 10, 20, 30, 40, 50, and 60 minute postexercise. Pre- to postexercise plasma cortisol increased in all exercise trials, except 60/90. Increases in 55/80 remained above pre-exercise levels for the entire postexercise period. Salivary cortisol increased from pre- to postexercise in FAT and 55/80 trials only. Once elevated after 55/80, it remained so for the postexercise period. Plasma testosterone increased from pre- to postexercise in all trials except 55/80. Saliva testosterone increased from pre- to postexercise in all trials with the longest elevation occurring after 55/80. Area under the curve analysis indicated that the exercise response of salivary hormones was greater in all cycle trials (cortisol) and in the 60/90 and 55/80 trials (testosterone) compared with the other trials. This study indicates that the 55/80 cycle protocol induces a prolonged salivary and plasma cortisol and salivary testosterone response compared with the other trials and so may be a useful diagnostic tool of overreaching.     

Specificity studies of monoclonal and rabbit antibodies raised against steroid glucuronides

Monoclonal and rabbit antibodies raised against estrone-3-glucuronide and pregnanediol-3 alpha-glucuronide have been studied with respect to their ability to bind free estrone and its conjugates or free pregnanediol and its conjugates, respectively. High titre and high specificity were observed with monoclonal antibodies produced against pregnanediol-3 alpha-glucuronide, whereas the monoclonal antibodies produced against estrone-3-glucuronide were not so specific when compared with the corresponding rabbit antibodies. Both monoclonal and rabbit antibodies had affinity constants in the range of 10(9)--10(10) liter/mole.     

The effect of human chorionic gonadotropin on plasma steroid levels in young and old men

Seven men, 21–30 years old, and six men, 72–90 years old, were given human chorionic gonadotropin (HCG), 3,000 units a day for four days. The concentration of 17β-estradiol (1), estrone and testosterone were measured in plasma samples drawn before and during the course of HCG administration. The administration of HCG resulted in higher levels of both 17β-estradiol and testosterone in the younger as compared to the older men although the percentage increases over baseline levels were similar in both groups. HCG administration resulted in similar, absolute and relative increases of estrone in both young and old men. The levels of 17β-estradiol were higher on day 3 as compared to day 5 in young men. The relative ability to respond to exogenous gonadotropins appears to be preserved despite ageing and loss of libido and potentia. The absolute response is, however, somewhat less in old men as compared to young.     

Plasma FSH and LH in prepubertal Booroola ewe lambs

Basal plasma concentrations (four 30-min samples) and GnRH-induced release of gonadotrophins were measured every 15 days between 30 and 90 days and at 110 days of age in Merino ewe lambs from the prolific Booroola ('B') flock (n = 18-23), the medium prolificacy ('T') flock (n = 14-20), and the 'O' flock (n = 4-8) of low prolificacy. At ages of 30 and 45 days B ewe lambs had mean basal plasma FSH concentrations of 145 and 122 ng/ml which were significantly higher (P less than 0.01) than those seen in T (45 and 53 ng/ml), and O (39 and 38 ng/ml) flock ewes. Between 60 and 110 days of age there were no significant differences between genotypes. The increment in FSH concentrations above basal levels induced by the subcutaneous injection of 100 micrograms synthetic GnRH was only significantly (P less than 0.05) greater in B than T and O genotype ewe lambs at 110 days of age but not at other ages. The basal plasma FSH differences between the B, T and O genotypes at 30 and 45 days of age were not consistently related to the size of litter in which lambs were born. At 30 days of age the mean plasma LH concentration of B, T, and O flock lambs were 2.6 +/- 0.5, 1.2 +/- 0.6 and 0.7 +/- 0.8 ng/ml respectively. These differences were not significant. At later ages there were also no significant differences between the genotypes with respect to basal LH, and the increase in LH induced by exogenous GnRH was always similar for the three genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men

The aim of this study was to investigate the effect of 7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of steroid sexual hormones, gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone, estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B and lipoprotein(a) were measured before the beginning and shortly after the end of the steroid application. After the treatment, we noted the following significant changes: a decline of testosterone and estradiol levels, increase of LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total cholesterol levels was of the borderline significance. A slight but significant increase was found in apolipoprotein B and lipoprotein(a). The most expressive was the fall of the atherogenic index. We suggest that the gel containing 7-oxo-DHEA might be a suitable drug for improving the composition of the steroid and lipid parameters in elderly men.