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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 163 records · Page 9Linked to original sources

Effects of aminoglutethimide on adrenal steroid secretion.

Effects of various doses of aminoglutethimide (AG) alone upon adrenal steroidogenesis were studied in normal postmenopausal women, whereas the effects of combined treatment with aminoglutethimide in variable doses together with 40 mg of hydrocortisone were studied in postmenopausal women with advanced mammary cancer and compared to effects of treatment with cortisol alone. Despite the well known inhibitory effect of AG on cortisol biosynthesis, plasma cortisol levels were unaffected by AG in doses of 150-1000 mg/d, probably due to a compensatory increase in ACTH in subjects with an intact pituitary-adrenal axis. The aromatase system appeared to be very sensitive to inhibition by AG, a clearcut inhibition being shown at doses as low as 150 mg/d. Evaluated from the ratio of plasma oestrone (E1) to plasma androstenedione (AN), treatment with AG at a dose of 150 mg/d appeared to reduce the aromatase activity to 33% of the basal value; 250 mg/d resulted in a reduction to 20% and 1 g/d to 5% of basal values. Whereas AG at 150 mg/d did not appear to affect 11 beta-hydroxylase, the latter was clearly inhibited by 250 mg/d and even more so by 1000 mg/d, as indicated by the increase in plasma 11-desoxycortisol and 17-OH progesterone (17-OHP) levels. Due to the increase of the latter, their biosynthetic precursor, AN and to a lesser degree testosterone (TS) levels increased significantly during AG treatment at a dose of 250 or 1000 mg/d. delta 5 steroid levels remained practically unchanged, probably because 11-(as well as the 21-) hydroxylation concerns essentially the delta 4 pathway. During combined treatment with 500-1000 mg/d of AG and cortisol 40 mg/d, AN and TS were significantly higher than during treatment with cortisol alone, suggesting that cortisol had not completely blocked ACTH secretion. E1 and E2 levels were however lower than during treatment with cortisol alone, a consequence of the inhibition of the aromatase activity. Although at a dose of 500-1000 mg/d AG is a highly effective aromatase inhibitor, oestrogen levels during treatment with AG with or without concomitant administration of cortisol are still significantly different from zero. Therefore if one aims at complete elimination of any oestrogen effect, addition of an antioestrogen to AG treatment may be required.

Adrenal Cortex Hormones↗

Seasonal variation of plasma dehydroepiandrosterone sulphate and urinary androgen excretion in post-menopausal women.

Urinary levels of the glucuronides of androsterone, aetiocholanolone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 beta-androstane-3 alpha, 17 beta-diol, were determined in twenty-two-post menopausal women both in spring and in autumn--winter. In sixteen women dehydroepiandrosterone sulphate plasma levels were also measured. Plasma DHAS levels as well as urinary metabolite excretion values were significantly higher in autumn--winter than in spring. This seasonal variability should be taken into account in long-term studies involving adrenal hormone levels, excretion or metabolism. Moreover this seasonal variability might be of relevance for the cyclical growth rate of hormone dependent tumours such as breast cancer.

Adrenal Cortex↗

Androgen secretion after age 50 in both sexes.

Androgen production by both testes and adrenals decrease in old age; this is partly the consequence of a decrease in the metabolic clearance rate but plasma levels as well as their response to human chorionic gonadotropin (HCG) and adrenocorticotropic hormone stimulation, respectively, do also decrease. As far as testicular androgen levels are concerned, there exists a large interindividual variation of plasma levels even in old age, some elderly persons having levels comparable to those found in young adults. Others have clearly decreased levels. Causes contributing to their variability are general health, physical and sexual activity, smoking habits, obesity, genetic factors, and intake of drugs. Although in exceptionally healthy persons, both physically and sexually active, testosterone levels may, therefore, not decrease in old age, in the elderly population at large, such a decrease does occur, even when all other factors influencing their levels are controlled. The decrease in testicular androgen secretion appears to have a primary testicular origin as luteinizing hormone levels are slightly, but significantly, increased and the response to HCG decreased.

Adrenal Glands↗

Immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) in human cord blood: high circulating serum levels but possible non-identity with hypothalamic TRH.

Levels of immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) were measured in paired maternal and umbilical cord serum samples (n = 45) and in serum of non-pregnant women (n = 63), using a sensitive and specific radioimmunoassay. In all pairs IR-TRH LM in venous cord serum (mean 91.3 pg/ml, range 20-270) was markedly elevated as compared to maternal serum (mean 13.5 pg/ml, range 0-37, P less than 0.001, the maternal levels being similar to those in non-pregnant women (mean 12.0 pg/ml, range 0-39, P greater than 0.1). In 23 cases IR-TRH LM was also measured in arterial cord serum: arterial and venous cord levels were highly significantly correlated (r = 0.904) with higher arterial levels in 22 out of 23 cases (mean 117.8 pg/ml, range 32-280 and 90.6 pg/ml, range 20-270, P less than 0.001), suggesting that cord IR-TRH LM is not of placental origin. There was no correlation between individual levels of IR-TRH LM and either TSH, T4, T3 or FT4 levels in either maternal or cord serum. Agar gel electrophoresis and equilibrium dialysis of adult and cord serum pre-incubated with [125I]TRH or [3H]TRH revealed no protein binding. Cord IR-TRH LM was immunologically, as well as in paper electrophoresis and in gelfiltration, indistinguishable from synthetic and hypothalamic TRH. In vitro degradation of synthetic TRH was much slower in cord serum as compared to maternal and control serum (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Plasma androgen levels after subcapsular orchiectomy or estrogen treatment for prostatic carcinoma.

In this study evolution of plasma androgen levels in patients with advanced prostatic carcinoma, treated by either subtotal bilateral orchiectomy or estrogens, was studied in order to determine whether subcapsular orchiectomy results in complete elimination of testicular testosterone secretion and whether in subsequent months there occurs any reactivation of eventually remaining Leydig or increased adrenal androgen secretion. This study, performed on 40 patients having undergone bilateral subcapsular orchiectomy for prostatic carcinoma, shows that this intervention results in testosterone levels in the female range and that during the year following subcapsular orchiectomy there is no evidence for reactivation of Leydig cells or for increased adrenal androgen secretion as evaluated from plasma testosterone, androstenedione, and dehydroepiandrosterone sulphate levels. In patients treated with estrogens we found no evidence for stimulation of adrenal androgen secretion, whereas in neither group of patients with prostatic carcinoma we found evidence for increased androgen levels at the time of recurrence of the carcinoma.

Androgens↗

Metabolic effects of the triphasic oral contraceptive Trigynon.

Effects of Trigynon, a triphase low-dose oral contraceptive, containing ethinylestradiol and l-norgestrel in various proportions, on testosterone binding globulin, transcortin, thyroxine, free testosterone, free cortisol and free thyroxine as well as on plasma lipids and glucose tolerance were studied in 12 normal women treated for 3-6 months. Trigynon appears to have dominant estrogenic effects as evidenced from the increase in transport proteins and the decrease in free testosterone concentration. Plasma lipids were not significantly influenced; glucose tolerance was slightly, but not significantly decreased.

Adult↗

Adrenocortical function in old age: response to acute adrenocorticotropin stimulation.

To elucidate the controversial point whether, in analogy with delta 5-steroid secretion, adrenal delta 4-steroid secretion is significantly decreased in elderly persons, we studied the response of plasma levels of both delta 5-steroids (dehydroepiandrosterone, 17-hydroxypregnenolone, and pregnenolone) and delta 4-steroids (cortisol, androstenedione, 17-hydroxyprogesterone, and progesterone) to acute ACTH stimulation in four groups of young and elderly males and females, respectively. To study the possible influence of sex hormones on adrenocortical function in elderly persons, we performed the same study in male with prostatic carcinoma treated with estrogens. The data show that in elderly persons, the response of plasma delta 4-steroids to ACTH stimulation is comparable or higher than that in young subjects, whereas the response of delta 5-steroids is significantly decreased; estrogen treatment does not change this pattern. It is concluded that in elderly persons adrenal delta 4-steroid secretory capacity is unimpaired, whereas delta 5-steroid secretion is significantly decreased. The responsible mechanism remains to be elucidated.

17-alpha-Hydroxypregnenolone↗

Prolactinomas, testosterone-binding globulin, and androgen metabolism.

To study the mechanism by which PRL might influence the metabolism of androgens, the testosterone-binding capacity of testosterone-estradiol-binding globulin (TeBG) as well as the free testosterone (T) fraction were determined in patients with prolactinoma. In untreated patients with prolactinoma, the TeBG capacity was decreased and the free T fraction was increased. Whereas in males, the plasma (free) T concentration was decreased, the apparent free T concentration was increased in women. The increased free T fraction had as a consequence an increase in MCRs of both T and 5 alpha-androstan-17 beta-ol-3-one; the MCR of androstenedione was normal. It is concluded that besides the well known factors, such as estrogens, androgens, and thyroid hormones, PRL appears, at least in prolactinoma patients, to influence the TeBG level.

Adenoma↗

Plasma levels of ethinylestradiol (EE) during cyclic treatment with combined oral contraceptives.

The purpose of the present study was to extend the still limited data concerning ethinylestradiol (EE) plasma levels after repeated daily ingestion of a combination pill during the course of classical cyclic treatment. Plasma EE levels were followed in 13 volunteers throughout, in total, 19 treatment cycles with either a 50 ug EE (+ 125ug d-norgestrel) or a 30 ug (+ 150ug d-norgestrel) containing oral contraceptive. In addition, single plasma EE determinations were performed in 110 chronic oral contraceptive users. Whereas different patterns in plasma EE levels (sampling 24 hours following last pill ingestion) were observed among the different volunteers, the mean levels increased progressively during treatment and reflected closely the differences in dosage. The values obtained in the volunteers at the end of the treatment cycle showed important interindividual variations. The findings during a first treatment cycle or during the following ones were similar and for different treatment cycles in the same patient, the patterns in plasma EE levels were consistent. The results for single plasma determinations in chronic contraceptive users (sampling between 8th and 21st day of treatment cycle, 9 to 24 hours since last pill ingestion) showed more pronounced interindividual variations, the individual EE levels being not correlated to parameters such as body weight, body surface, months of oral contraception prior to the study, sex hormone binding capacity or day of the cycle. However, significant differences in mean plasma EE levels were noticed for patients treated with different commercial preparations with identical EE content, suggesting the existence of differences in bioavailability. The relevancy of plasma EE determinations is discussed and from the results of the present study, it is concluded that a strictly standardized time of sampling is an absolute condition for obtaining interpretable results.

Contraceptives, Oral↗

Associations between sex hormones, thyroid hormones and lipoproteins.

1. A study of 150 middle-aged male industrial employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both serum testosterone and alcohol intake, and significant negative correlations between HDL cholesterol and both serum thyroxine and obesity. These associations persist when examined by multiple linear regression, indicating their independence. 2. Significant positive correlations are also shown between plasma triglyceride levels and both obesity and serum thyrotropic hormone (TSH) levels. 3. There are no evident relationships between serum oestrone or oestradiol and either HDL cholesterol or triglyceride levels, nor between any of the hormones and either total or low-density-lipoprotein (LDL) cholesterol. 4. Because of the potential importance in relation to coronary heart disease prevention, further studies are needed to try and understand the mechanisms of the associations between HDL cholesterol and obesity, alcohol intake and thyroid and sex hormone levels.

Alcohol Drinking↗