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Biomedical subjects

C Longcope

Publications and source records attributed to C Longcope.

At least 163 records · Page 9Linked to original sources
PubMed1982

Androgen and oestrogen dynamics in hyperthyroidism.

Using constant infusions of [3H]testosterone and [14C]oestradiol or [3H]androstenedione and [14C]oestrone the dynamics of androgen and oestrogen metabolism and production in patients with hyperthyroidism were measured. The metabolic clearance rates of testosterone and oestradiol were decreased but those of androstenedione and oestrone were within the normal range. The conversion ratios of testosterone to androstenedione and of testosterone to dihydrotestosterone (DHT) were decreased whereas those of androstenedione to testosterone and androstenedione to DHT were increased. These changes could be explained by increased serum levels of sex hormone binding globulin which binds testosterone and DHT but not androstenedione. The fraction of androstenedione infused into and measured as oestrone in the blood was normal in seven out of nine subjects and the fraction of testosterone infused and measured as oestradiol was normal in all nine subjects. The production rates of testosterone and oestradiol were in the normal range but the production rates of androstenedione and oestrone were raised in half the subjects.

Adult↗
PubMed1982

Systemic lupus erythematosus in men. Genetic and endocrine features.

Sixteen men with systemic lupus erythematosus (SLE) were examined to assess their genetic and hormonal status. The results of buccal smears in 13 patients examined were normal. Hormonal profiling was done in eight patients receiving no steroid therapy. Four patients had elevated plasma estradiol levels (30, 35, 55, and 103 pg/mL; normal, 12 to 23 pg/mL) and elevated plasma estrone levels (115, 150, 155, and 160 pg/mL; normal, 48 to 100 pg/mL). One patient had a decreased serum testosterone level (134 ng/dL; normal, 300 to 1,000 ng/dL), with an elevated luteinizing hormone (LH) level (4.2 ng/mL; normal, 1.6 to 4.0 ng/mL). One patient had an elevation in both levels of serum follicle-stimulating hormone (17.6 ng/mL; normal, 1 to 5 ng/mL) and LH (10.0 ng/mL). Two patients given infusions of 3H-androstenedione and 14C-testosterone had normal findings from kinetic studies of these hormones. Hyperestrogenemia and hypoandrogenemia observed in some men with SLE suggest that female sex hormones may create an immunologic milieu that facilitates the autoimmune phenomena.

Adolescent↗
PubMed1981

Biologic activity of the iodoestrogens and their use in breast cancer.

Several iodinated estrogens, 6-iodoestra-1,3,5(10), 6-tetraene-3, 17 beta-diol (4) 16 beta-iodo-estradiol (3) were shown to displace 3H-estradiol (1b) from the uterine cytosol receptor by a competitive type of inhibition. The three compounds translocated the cytosol receptor to the nucleus in vitro and increased mouse uterine weight in vivo. In all tests the relative activities were 16 alpha-(2a) greater than 16 beta-(3a) greater than 6-(4a). When the compounds were made with [125I] the 16 alpha-[125I]-iodoestradiol (2b) bound with high affinity, Kd = 0.4 x 10(-10), to the 8S cytosol receptor. No high affinity binding could be demonstrated for the 6-[125I]-iodoestratetraene (4b). In in vivo experiments following the administration of 16 alpha-[125]-iodoestradiol (2b) to rats, high levels of radioactivity were found in the uterus, liver and thyroid but only in the liver and thyroid following administration of 6-[125I]-iodoestratetraene (4b). After administration of (2b) to rats with DMBA-induced mammary tumors, no tumor concentration of radioactivity could be detected by imaging. When (4b) was administered similarly, radioactivity could be detected in some of the tumors by imaging. The radioactivity was associated with non-specific 4S proteins.

Animals↗
PubMed1981

Production rates of androgens and oestrogens in post-menopausal women.

The production rate (PR) values of delta 4-androstenedione (A), testosterone (T), oestrone (E1) and oestradiol (E2) have been determined in a large group of post-menopausal women following constant infusions of radiolabelled hormones and radioimmunoassay of endogenous steroid concentration. The mean +/- SE age was 64 +/- 2 yr, ranging from 46 to 91 yr and the mean +/- SE weight was 144 +/- 4 lb. When the PR values were related to age by linear regression analysis no significant correlation could be found for PRA, PRT or PRE1 and the age of the subjects. There was, however, a significant correlation between PRE2 and age. There was a significant correlation between the PR values for each of the four steroids and the weights and body surface areas of the subjects. In addition, PRA correlated directly with both PRT and PRE1 in these subjects in which both PR values were measured. The PR values for each steroid were significantly smaller in the post-menopausal women compared to the mean PR values of a large group of pre-menopausal women. We conclude that age, per se, does not appear to influence the PR values for A, T and E1 but does for E2. The subjects weight, however, has a major influence for the PR values of all four steroids.

Age Factors↗
PubMed1981

Effect of peripheral sex steroid metabolism on pituitary gonadotropin reserve of women with hypothalamic amenorrhea.

Women with hypothalamic amenorrhea without evidence of pituitary tumor were studied to ascertain (1) whether affected patients have altered pituitary sensitivities and reserves to a constant gonadotropin-releasing hormone (GnRH) infusion and (2) whether altered sex steroid metabolism contributed to altered pituitary synthesis or secretion of gonadotropin. Women with hypothalamic amenorrhea displayed abnormal gonadotropin reserves without altered pituitary sensitivity to GnRH. Those altered reserves may have reflected, abnormally low estradiol levels, which directly or indirectly affected, pituitary gonadotropin synthesis. However, sex steroid metabolism or normally cycling and amenorrheic women were not significantly different. The ovaries of both groups of patients were equally reactive to stimulation with endogenous gonadotropin, as reflected by circulating estradiol levels attained at the end of the GnRH infusion.

Adult↗
PubMed1981

Tissue metabolism of estrogens in the female rhesus monkey.

The overall MCRs and [rho]BB values (fraction of infused precursor measured in blood as product) and individual tissue extractions and conversions were measured in the follicular and luteal phases of normal cycling female rhesus monkeys using constant infusions of [3H]estradiol ([3H]E2) and [14C]estrone ([14C]E1). During the infusions, blood samples were obtained from the femoral artery and veins draining the splanchnic tissue, kidney, head, arm, and uterus. The overall mean (+/- SE) MCR for E2 (214 +/- 17 liters/day) was significantly less than the MCR for E1 (295 +/- 13 liters/day). There were no differences in the MCR measured in the follicular or luteal phases of the cycle. The [rho]BB values were greater for the fraction of infused E1 measured in blood as product E2 [rho]E1, E2, BB; (0.25 +/- 0.02) than for [rho] E1, E2, BB (0.11 +/- 0.01). Neither value was affected by the time of the cycle. The extractions (that fraction of steroid measured in arterial blood entering a tissue which is metabolized and not measured as that steroid in venous blood draining the tissue) across the splanchnic tissues were the largest of the tissue extractions measured (0.63 +/- 0.05 for E2 and 0.73 +/- 0.10 for estrone). The arm, uterus, kidney, and head had lower extractions, and the extraction of E2 was always lower than that of E1, probably due to the specific globulin binding of E2. Interconversion of the estrogens occurred across each tissue bed but reflected, in general, only a small portion of the total extraction, especially for the splanchnic tissue. There was no apparent difference in any of the transtissue conversions measured in the follicular as compared to the luteal phase. The administration of pharmacological amounts of dexamethasone to three monkeys resulted in a marked increase in the MCR of estradiol and a slight decrease in the MCR of estrone. Individual tissue extractions and transtissue conversions showed no consistent alteration after dexamethasone.

Animals↗
PubMed1981

The relationship of androgen to the thyrotropin and prolactin responses to thyrotropin-releasing hormone in hypogonadal and normal men.

Fluoxymesterone, an androgen not converted to estrogen, caused a significant decrease in the TSH response to TRH in 11 men with primary hypogonadism [maximum change in TSH: before treatment, 11.3 +/- microU/ml (mean +/- SE); 8.9 +/- 1.0 after 2 weeks (P less than 0.001); 8.2 +/- 1.1 after 6 weeks (P less than 0.01)]. There was a significant fall in serum T4-binding globulin (TBG) (measured directly by RIA) without a change in the free T4 or free T3 index. Fluoxymesterone had no effect on the PRL response to TRH in hypogonadal men. The results suggest that 1) androgen per se is at least partly responsible for the lower TSH response to TRH in men compared to women and 2) androgen is not a cause of the lower PRL response to TRH in men.

Adult↗
PubMed1980

Steroid secretion by the postmenopausal ovary.

The concentrations of certain steroids in arterial and ovarian venous blood were measured in 42 postmenopausal women undergoing hysterectomy for uterine disease. A concentration gradient across the ovary was found for testosterone in 21 women, for androstenedione in 16, for estradiol in 15, for estrone in 8, and for dehydroepiandrosterone in 3. On the basis of postualated ovarian blood blow the gradient would result in a major contribution to the blood production rate for testosterone in about 50% of women and for estradiol in less than 20%. For androstenedione, dehydroepiandrosterone, and estrone the gradients did not signify important ovarian secretion. There was no evidence for secretion of dihydrotestosterone, estrone sulfate, or dehydroepiandrosterone sulfate. There were no apparent clinical correlates to indicate in which women the ovary was secreting steroids.

Androstenes↗
PubMed1980

Metabolic clearance rates of androgens and oestrogens in ageing women.

Using the constant infusion technique we have measured the metabolic clearance rates (MCR) for delta 4-androstenedione (A), testosterone (T), oestrone (E1) and oestradiol (E2) in a large group of post-menopausal women. Their mean +/- SE age was 64.5 +/- 1.6 yr, their ages ranged from 46-90 yr. When the MCRs for each steroid were related to age by linear regression analysis no significant correlation was found for any of the steroids. Similarly, when the women were grouped according to their age by decade, the mean MCR for each steroid showed no trend with increasing age. There was no difference in the MCRs for A, T and E1 of the post-menopausal women and a large group of pre-menopausal women. However, there was a significant decrease in the mean MCR for E2 between the two groups which is probably related to the marked decrease in circulating E2 in post-menopausal women. We conclude that for these steroids age, per se, does not appear to be a major determinant of the MCR.

Adult↗
PubMed1980

Androgen and estrogen conversion rations in aging women.

Androgens and estrogens labeled with 3H- and 14C- have been infused at constant rates into postmenopausal women whose ages ranged from 45--90 yr, and who were 1--40 yr postmenopausal. The conversion ratios (ratio of concentrations of radioactivity as infused precursor to product steroid) for interconversions of androstenedione to testosterone, for the conversions of androstenedione and testosterone to dihydrotestosterone and for the interconversions of the estrogens were calculated. There was no trends in the conversion ratios with age and the mean values for these ratios in these postmenopausal women did not differ significantly from their respective values in a group of normal, healthy, reproductive-aged women. Our data are compatible with the conclusion that the overall activities of certain 17 beta-dehydrogenases and 5 alpha-reductases do not decrease appreciably with age.

Aged↗
PubMed1980

Inhibition of peripheral aromatization by aromatase inhibitors, 4-hydroxy- and 4-acetoxy-androstene-3,17-dione.

To determine the effect of aromatase inhibitors on peripheral aromatization, male rhesus monkeys were infused with [7-3H]androstenedione and [4-14C]estrone before and during treatment with 4-hdyroxy-androstene-3,17-dione (50 mg/kg each; four monkeys) or 4-acetoxy-androstene-3,17-dione (700 mg each; two monkeys). In all six monkeys, no specific effects on the MCRs of androstenedione and estrone, the interconversion of androgens or estrogens, or androstenedione conversion to dihydrotestosterone were noted. In five of the six animals, aromatization rates were reduced by up to 97% of control values. The results demonstrate that these compounds inhibit peripheral aromatization and, together with our other results, suggest that aromatase inhibitors may be a useful treatment for estrogen-dependent cancer.

Androgens↗