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Biomedical subjects

C Longcope

Publications and source records attributed to C Longcope.

At least 181 records · Page 10Linked to original sources
PubMed1979

Uterine metabolism of gonadal steroids during the menstrual cycle.

The metabolic clearance rate and uterine extraction of (3H)progesterone, (3H)estradiol, and (14C)estrone were studied at the time of hysterectomy in six women on or before day 12 of the menstrual cycle, in three women after day 12, and in one postmenopausal woman. The metabolic clearance rates of progesterone, estradiol, and estrone were in the same range as for normal women as previously reported by us. The uterine extraction for progesterone ranged between 12% and 37% on or before day 12 and 0% to 5% after day 12, and was 7.4% in the postmenopausal woman. The uterine extraction of estradiol was 0% to 25% on or before day 12, and 0%, 4%, and 22% after day 12 and was 18% in the postmenopausal woman. The uterine extraction of estrone was 7% to 24.5% on or before day 12 and 0% after day 12 and was 18% in the postmenopausal woman. The across-uterine interconversion of estradiol to estrone was 0% to 2.7% and of estrone to estradiol 0% to 2.6%. Both conversions appeared to be independent of the day of the menstrual cycle. The results suggest that the uterine metabolism of progesterone and estrone and perhaps estradiol is lower in the luteal phase of the cycle as compared to the follicular phase and that the conversion of estradiol to estrone may not be a major reaction of estradiol metabolism in the human uterus.

Adult↗
PubMed1979

Iodoestrogens, syntheses, and interaction with uterine receptors.

The rationale for undertaking the present study was to evaluate the utility of iodoestradiol analogs made highly radioactive with iodine isotopes in (a) the non-invasive differentiation of estrogen-dependent from estrogen-independent breast tumors, (b) spread of metastases containing estrogen receptors, and (c) potential application in therapeutic irradiation of target tissues. In the present paper, the model syntheses of a number of nonradioactive 127I-estrogen analogs are described. The analogs were tested for their ability to displace (compete with) [3H]estradiol from receptor sites. The most active compounds, 16beta-iodoestra-1,3,5(10)-triene-3,17 beta-diol (17) and 6-iodoestra-1,3,5(10),6-tetraene-3,17 beta-diol (10b), showed a relative binding affinity of 0.57 and 0.49, respectively.

Animals↗
PubMed1979

Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis.

Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis.

Adult↗
PubMed1979

Androgen and estrogen metabolism in male rhesus monkeys.

Using constant infusions of 3H-labeled androgens and 14C-labeled estrogens, the dynamics of androgen and estrogen metabolism have been studied in male rhesus monkeys. The mean (+/-) MCR, as measured in whole blood, for testosterone (T; 140 +/- 10 liters/day) was significantly smaller than the MCRs for androstenedione (A), estrone (E1), and estradiol (E2; 650 +/- 8, 1010 +/- 160, and 500 +/- 20 liters/day, respectively). These findings are compatible with the specific globulin binding of T in this species. The mean blood productions were 0.42 +/- 0.11 and 0.55 +/- 0.04 mg/day for A and T and 40 +/- 16 and 13 +/- micrograms/day for E1 and E2, respectively. The interconversions of the androgens [fractional conversion rates of A to T ([rho]A,TBB) and T to A ([rho]T,ABB)] were not different but were lower than the interconversions of the estrogens ([rho]E1,E2BB and [rho]E2,E1BB). The mean [rho]T,E2BB values were 0.015 +/- 0.001 and 0.0024 +/- 0.0003, which are remarkably similiar to those values in men. Administrations of PMS gonadotropin did not alter any measured values of androgen or estrogen metabolism, hCG resulted in a decrease in the conversion ratio of A to T, T administration increased the MCR of T, and estrogen administration resulted in no changes. The aromatization rate remained unaffected by all treatments.

Androgens↗
PubMed1978

Hormones: beneficial or dangerous to the aged?

Postmenopausal women lose 75-85 percent of estrogen and progesterone production compared with that in their reproductive years. The marked decrease in estrogen results in changes in the uterus, cervix, vaginal lining, glandular breast tissue, and the rate at which bone loses thickness. Some of these changes result in symptoms which range from unpleasant to disabling. Many of the symptoms can be alleviated by treatment with estrogens. However, recent reports have been linking estrogen usage with carcinoma of the uterus. Postmenopausal women should be treated with estrogens when the situation demands, but the dosage should be kept as low as possible and progestational agents should also be administered.

Aged↗
PubMed1978

Aromatization of androgens by muscle and adipose tissue in vivo.

[7-3HA1Androstenedione and [4-14C]estrone or [7-3H]testosterone and [14C]estradiol were infused at constant rates into brachial arm veins of 15 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle, and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In seven men the mean +/- SE value for the fractional conversion of androstene tissue. In eight men the mean +/- SE value for the fractional conversion of testosterone to estradiol was 0.0007 +/- 0.0001 for muscle and 0.0012 +/- 0.0002 for adipose tissue. Both of these values were significantly (P less than 0.01) less than the respective values of androstenedione aromatization to estrone. If constancy of tissue aromatization throughout the body is assumed, the muscle accounts for 25-30% and adipose tissue for 10-15% of the total extragonadal aromatization of androgens to estrogens.

Adipose Tissue↗
PubMed1978

Estriol production rates and breast cancer.

We have infused [6,7-3H]estrone or [6,7-3H]estradiol and [4-14C]estriol into seven women who had had breast cancer and into five normal postmenopausal women. We measured the endogenous concentrations and the metabolic clearance rates of estrone, estradiol, and estriol and calculated the blood production rates for these steroids in each group. There were no significant differences between the respective measurements for each group. Our data does not support the argument that physiological amounts of estriol are protective against breast cancer development in women.

Adult↗
PubMed1978

Effect of chronic administration of estrogen, androgen, or both on serum levels of gonadotropins in adult men.

Ethinyl estradiol (50 micrograms/day) or fluoxymesterone (10 or 20 mg/day), chosen because each is orally active and because fluoxymesterone is probably not converted to an estrogen, were given alone and in combination to adult men over several weeks. Measurements were made of serum FSH, LH, testosterone, and estradiol. The estrogen given alone suppressed serum FSH while the androgen given alone did not; however, the androgen may have enhanced the suppressive effect of the estrogen on the serum FSH. Neither steroid alone changed the serum LH but both together suppressed it. The estrogen alone decreased the serum testosterone, an effect probably mediated by the concomitant fall in serum FSH and a resulting decrease in sensitivity to the constant level of LH; a direct effect of estrogen on the testis seems less likely. The doses of estrogen and androgen used probably had a biologic effect equal to or somewhat above that of endogenously produced estrogen and androgen and thus reflected the maximum physiological effects of the endogenous steroids. Thus, in the chronic physiological control of FSH and LH in adult men, these data indicate that (1) testosterone alone, as an androgen, has little effect on FSH or LH, (2) estradiol (or total estrogen) has a greater suppressive effect on FSH than on LH and by its effect on FSH may indirectly regulate the secretion of testosterone, and (3) testosterone and estradiol together may be involved in the regulation of both FSH and LH.

Adult↗
PubMed1978

The relationship of changes in serum estradiol and progesterone during the menstrual cycle to the thyrotropin and prolactin responses to thyrotropin-releasing hormone.

The responses of serum TSH and PRL to TRH (500 microgram) were studied in normal young women in the early follicular, periovulatory, and midluteal phases of the menstrual cycle in order to examine the relationship of these responses to the levels of estradiol relationship of these responses to the levels of estradiol (E2) and progesterone. Each woman was studied twice in each phase in order to assess intraindividual variability. There was no significant difference in either the TSH or PRL responses among the phases of the menstrual cycle nor was either response affected by the periovulatory rise in E2 or by the luteal rise in both E2 and progesterone. Thus, the interpretation of the TSH and PRL responses to TRH in normal women is not affected by the menstrual cycle although both responses are greater in women that in men. Both the peak TSH and peak PRL after TRH were highly correlated with the basal levels of TSH (r = 0.85; P less than 0.01) and PRL (r = 0.67; P less than 0.01), respectively, indicating that the TSH and PRL responses to TRH in women are directly proportionate to the basal levels of the respective hormones, as previously shown for the TSH response in men. The mean intraindividual variability (coefficient of variation) of the TSH response to TRH was 18%, but ranged as high as 56%, while that of the PRL response was 16% and ranged up to 31%; variability was not affected by the phase of the menstrual cycle. The normal range of the peak TSH after TRH in women is 7-33 microU/ml (mean +/- 2 SD); however, because of the variability, a normal woman may sometimes have a peak TSH after TRH as low as 4 microU/ml. Repeating the test will result in a normal value if the woman is truly normal. Similarly, the normal peak PRL after TRH in women is 22-111 ng/ml (mean +/- 2 SD); usually, however, the lower limit is 30 ng/ml with lower values due to intraindividual variation. The data suggest that the higher average level of E2 in women compared to women, but that the cyclic changes in serum E2 or progesterone in women have little or no additional effect.

Adult↗
PubMed1978

Relationship between urine and plasma estrogen ratios.

Normal young and postmenopausal women were placed into groups according to the ratio of the estrogens in their urine. Women whose ratio was greater than 1.3 if young and greater than 3.2 if postmenopausal were compared to women whose ratio was less than 0.7 and less than 2.1 for young and postmenopausal, respectively. Between the respective high- and low-ratio groups, there were no significant differences for circulating levels of estriol, metabolic clearance rates of estriol, or blood production rates of estriol, estrone, or estradiol. Women who had had breast cancer were compared to a group of normal controls and were also found to have similar blood production rates for estriol, estrone, and estradiol. The ratios of the blood production rates of estriol to estrone and estradiol were similar for the high and low groups for young and postmenopausal women and also between the breast cancer women and their controls. It appears, therefore, that the difference in urinary estrogen ratios is primarily due to different pathways of metabolism of the free circulating estrogens and not to differences in the production rates of the estrogens. Estriol is produced at only 10% the rate of estrone and estradiol.

Breast Neoplasms↗
PubMed1977

Blood production rates of estrogens in women with differing ratios of urinary estrogen conjugates.

On the basis of the ratios of the estrogen conjugates in their urine (estriol/estrone + estradiol: E3/[E1+E2]), 19 women were divided into two groups: 9 women had ratios less than 0.6 and 10 women had ratios greater than 1.3. All women had measurements made of endogenous estrogens in their plasma by radioimmunoassay. They were then given constant infusions of 3H-estrone, 3H-estradiol and 14C-estriol during days 5-7 and days 20-22 of their cycles, and metabolic clearance rates (MCR) and blood production rates (PB) of estrone, estradiol and estriol were determined. Despite the wide disparity in their ratios of urinary estrogens, no differences could be found between the groups for the MCR's and PB's for all estrogens at either time of the cycle. The mean ratios of PB's (PB3/[PB2+PB1]) of estrone, estradiol and estriol ranged from 0.07 to 0.10 for each group during the cycle. The amounts of estriol entering the blood are small compared to the amounts of estrone and estradiol and do not correlate with the ratios of their urinary conjugates.

Adult↗
PubMed1976

The in vivo metabolism of androgens by muscle and adipose tissue of normal men.

Androstenedione and testosterone labeled with 3H and 14C were fused simultaneously at constant rates into the brachial arm vein of 10 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contra-lateral to the infusion. In the 10 men the mean +/- SE value for the fractional metabolism of adrostenedione by muscle is 0.20 +/- 0.30 which is not different from the mean value for the fractional metabolism by androstenedione by adipose tissue, 0.29 +/- 0.04. The mean value for the metabolism of testosterone by muscle, 0.04 +/- *.01, is significantly less than the metabolism by adipose tissue, *.11 +/- 0.01. Interconversion between adrostenedione and testosterone occurs in both tissues. The mean value for pA,T A,M is 0.024 + 0.005 and for pA,T A,AT is 0.024 +/- 0.005. The mean value for pT,A A,M is 0.005 +/- 0.003 and for pT,A A,AT is 0.008 +/- 0.003. The fractional metabolism of these androgens by these tissues is similar to the fractional metabolism of estrone and estradiol by these same tissues. Muscle appears to contribute about 5-12% of the overall metabolism of androstenedione and testosterone and 10-15% to theoverall conversion of androstenedione to testosterone. Adipose tissue contributes about 2-7% of the overall metabolism of these androgens and 5-10% of the overall conversion of androstenedione to testosterone, but less than 2% to the overall conversion of testosterone to androstenedione. In normal men, muscle appears to be more important to the metabolism of androstenedione and testosterone than is adipose tissue.

Adipose Tissue↗
PubMed1976

Metabolism of radioactive 17 beta-estradiol 3-methyl ether by humans.

A mixture of 2-3H and 4-14C-17beta-estradiol 3-methyl ether was administered orally to a man and to a woman. 34 and 35 percent of the 3H was liberated into the body water of the man and of the woman, respectively, reflecting reactions involving position 2. The metabolism of estradiol methyl ether was qualitatively similar to that observed previously for radioactive estradiol administered intravenously to the same subjects, as judged by the measurement of various urinary metabolites by reverse isotope dilution. Evidence was obtained for hydroxylation at position 2 without demethylation by the isolation of urinary 2-hydroxyestrone 3-methyl ether which retained 33% of the original 3H. This 3H was presumably at position 1, resulted from an NIH shift which does not occur during hydroxylation of estrone or estradiol. This was confirmed by subsequent administration of a mixture of 4-14C and 3H-(methoxyl)-estradiol 3-methyl ether to the man. There was no evidence (by reverse isotope dilution) for 1-hydroxyestrone, 1-hydroxyestrone 3-methyl ether, 4-hydroxyestrone 3-methyl ether or 4-hydroxyestradiol 3-methyl ether as urinary metabolites of estradiol 3-methyl ether.

Adult↗
PubMed1976

The metabolic clearance and blood production rates of estriol in normal, non-pregnant women.

The metabolic clearance rate (MCR) and blood production rate (PB) of estriol have been measured in normal, non-pregnant women 21 to 65 years old. 6,7-3H-Estriol was administered as a pulse injection to 4 women between days 5-7 of their menstrual cycle. The disappearance of radioactivity as unconjugated estriol can be described as a function which is the sum of two exponentials. The initial component represents spread into and transfer from a space with a volume of 20.6 +/- 5.4 (SE) l. The mean value for the rate constant of total removal (reversible and irreversible) was 290.2 +/- 78.5 units/day of which 0.34 +/- 0.06 was irreversible. The mean MCRR was 990 +/- 70 l/day/m2. 4-14C-Estriol was infused at a constant rate for 3 1/2 hours to 13 women between days 5-7 of their cycle. The mean MCR was 2,100 +/- 100 l/day or 1,240 +/- 40 l/day/m2. Thirteen women received a constant infusion of 4-14C-estriol between days 20-22 of their cycle. The mean MCR was 2,100 +/- 115 l/day or 1,280 +/- 65 l/day/m2. The mean values for the two phases of the cycle were not significantly different (P greater than 0.1). The mean value for the MCR in 4 post-menopausal women studied in similar fashion was 1,890 +/- 95 l/day or 1,060 +/- 35 l/day/m2. The mean concentrations of estriol were 7.0 +/- 0.7 and 10.9 +/- 0.8 in the follicular and luteal phases of young women, respectively. The mean PB for women in the follicular phase was 14.0 +/- 1.6 mug/day and in the luteal phase was 22.7 +/- 1.9 mug/day. These values were significantly different (P less than 0.01). When the PB's for the 11 women studied in both phases of the cycle were compared the luteal phase values were significantly higher 0.02 greater than P greater than 0.01) using the paired t test. The PB in the 4 post-menopausal women ranged from 5 to 22 mug/day. While there was no difference between the MCR of estriol measured in the two phases of the cycle, the PB of estriol was significantly greater in the luteal phase. Estriol probably contributes little to the overall estrogenic activity in normal, non-pregnant, premenopausal women but could make a more significant contribution in some post-menopausal women.

Adult↗
PubMed1976

In vivo studies on the metabolism of estrogens by muscle and adipose tissue of normal males.

3H and 14C-Labeled estrone, estradiol, and estrone sulfate were infused at constant rates into brachial arm veins of normal men. In any one experiment, subjects generally received two estrogens, one 3H-labeled and one 14C-labeled. During the infusions, blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In 11 men the mean +/- SE value for the metabolism of estrone by muscle, rho1,0A,M(rho1,0A,M = fraction of estrone in arterial blood which is metabolized by muscle) is 0.17 +/- 0.02 which is not (P greater than 0.1) significantly different from the mean +/- SE value for the metabolism of estrone by adipose tissue, rho1,0A,AT, 0.22 +/- 0.02. Both tissues convert estrone to estradiol, rho1,2A,M(rho1,2A,M = fraction of estrone in arterial blood which is measured as estradiol in venous blood draining muscle) is 0.026 +/- 0.005 and rho1,2A,AT is 0.022 +/- 0.005. Both tissues metabolized estradiol, rho2,0A,M = 0.09 +/- 0.01 and rho2,0A,AT = 0.12 +/- 0.03, and for each tissue the metabolism of estradiol was significantly less than that of estrone (P less than 0.01). Estradiol was converted to estrone by both tissues; rho2,1A,M = 0.007 +/- 0.003 and rho 2,1A,AT = 0.017 +/- 0.003. For estrone sulfate, tissue metabolism could be demonstrated in only 2 of 5 infusions; the values being 0.04 and 0.03, and 0.04 and 0.03 in muscle and adipose tissue, respectively. In only 1 of 3 infusions was evidence obtained for the conversion, by muscle, of estrone sulfate to estrone, rhoS,1A,M = 0.003 and only in one of the 5 subjects was adipose tissue active in this conversion. In no instance were we able to show conversion of estrone sulfate to estradiol by either tissue. In only 1 of 3 infusions could we measure demonstrable conversion of estrone to estrone sulfate by adipose tissue, rho1,SA,AT = 0.02, and we could not demonstrate conversion of estrone to estrone sulfate by muscle or of estradiol to estrone sulfate by either tissue. Both muscle and adipose tissue metabolize and interconvert the free estrogens, estrone and estradiol. The total metabolism by both tissues accounts for 5-10% of the overall metabolic clearance rate of each steroid. The formation of estrone sulfate from estrone and estradiol and the hydrolysis of estrone sulfate occurs to only a minor extent in these tissues.

Adipose Tissue↗
PubMed1975

Estriol concentrations in plasma of normal, non-pregnant women.

Using a rabbit antisera directed against estriol-3-0-carboxy methyl ether complexed to BSA, an immunoassay for estriol (1) was developed. The mean plus or minus SE concentration of estriol in 18 women in days 5-7 of their cycle was 7.9 plus or minus 0.6 pg/ml which was significantly (P less than 0.01) less than the mean value of 11.1 plus or minus 0.8 pg/ml in 15 women in days 20-22 of the cycle. In 3 of 6 women in whom plasma samples were drawn frequently during their cycle, an estriol peak occurred coincident with the estradiol peak. In 3 women from whom plasma was obtained several times during the course of a day estriol levels did not appear to vary significantly. In 8 women who were on oral contraceptives the mean level of estriol was 7.6 plus or minus 1.5 pg/ml. In 8 post-menopausal women the mean level was 6.0 plus or minus 1.2 pg/ml which is significantly (P less than 0.01) less than the mean luteal phase value but not less (P greater than 0.1) than the follicular phase or oral contraceptive user values. We conclude that some of the circulating estriol is directly secreted by the ovary of normal women.

Adult↗
PubMed1975

Metabolism of 4-3-H- and 4-14-C-17alpha-ethynylestradiol 3-methyl ether (mestranol) by women.

A mixture of 4-3-H and 4-14-C-mestranol was administered orally to four women. Reactions involving position 4 were no greater than 1.7-3% of the dose as measured by liberation of 3-H into body water. The extent of de-ethynylation in vivo was no greater than 1-2% of the dose as measured by urinary estrone metabolites. Mestranol (0.7 and 0.32% of the dose), 17alpha-ethynylestradiol (6.6 and 11.3%) and 2-hydroxy-17alpha-ethynylestradiol (0.64 and 0.7%) were identified as metabolite aglycons by reverse isotope dilution after Ketodase hydrolysis of the urine from two of the women.

Administration, Oral↗