Christopher Longcope

Metabolic clearance and blood production rates of estrogens in postmenopausal women

Abstract With the use of the constant infusion technique, the mean metabolic clearance rate for estradiol in 5 women aged 70 to 88 was found to be 580 ± 30 L. per day per square meter. The mean metabolic clearance rate for estrone in 5 women aged 73 to 89 was 1,050 ± 70 L. per day per square meter. Both these represent a decrease of about 25 per cent compared to the corresponding clearance rates of these estrogens in young women. In 14 women aged 73 to 89, the mean plasma concentration of estradiol was 6.5 ± 0.7 pg. per milliliter, and that of estrone was 24.8 ± 3.5 pg. per milliliter. The calculated blood production rate for estradiol in these groups of postmenopausal women was 6 μg per day, and that for estrone was 40 μg per day. Direct secretion of estrogens would appear to be minimal in these asymptomatic postmenopausal women.

Decreased serum testosterone concentration in male heroin and methadone addicts

Abstract The serum concentrations of testosterone, estradiol-17β, FSH and LH were measured in 22 male subjects addicted to heroin or methadone. Serum testosterone concentration was decreased in many of these subjects without consistent abnormalities in the other hormones. It is suggested that decreased sexual function in male addicts may be partially due to a decrease in serum testosterone concentration.

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.

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

Abstract 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.

The effects of synthetic estrogens on the metabolic clearance and production rates of estrone and estradiol.

Abstract The metabolic clearance rates (MCR) of estrone (1) and estradiol were determined by pulse injections and constant infusions of 3 H-estrone and 3 H-estradiol in seven women taking mestranol-containing compounds and in seven women taking ethinyl estradiol-containing compounds. These results were compared with the results previously obtained in our laboratory (2, 3, 4, 5) in comparable women not taking these compounds. In the women taking mestranol the mean (± SE) MCR for estradiol, 750 ± 600 1/day/m 2 , was similar to our normal mean value, 790 ± 30 1/day/m 2 . However, the mean MCR for estrone was less 1,010 ± 60 1/day/m 2 than that in normals 1,230 ± 30 1/day/m 2 . In the women taking ethinyl estradiol the mean MCR for estradiol, 1,070 ± 60 1/day/m 2 was significantly ( P 2 was not different from the normal. Using an immunoassay to measure the concentrations of estradlol and. estrone in plasma, the mean level of estradlol in mestranol users was 40 ± 7 Pg/ml and in ethinyl estradlol users 69 ± 4 pg/ml. The mean calculated production rate for estradlol in the mestranol users was 47 ± 8 μ g/day and in the ethinyl estradlol users was 120 ± 22 μ g/day. The mean calculated, production rates for estrone were 71 ± 12 and 93 ± 12 μ g/day in the respective groups. Thus while mestranol appears to have little effect on endogenous estrogen metabolism, the use of ethinyl estradiol appears to increase the MCR of estradlol, but not of estrone. The MCR of estradlol returns to the normal range when ethinyl estradlol is stopped.

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.

The secretion of estrone and estradiol-17β by human testis

Abstract Samples of spermatic and systemic venous blood were obtained in 8 young males undergoing renal vein catheterization for essetial hypertension. Analysis of these bloods by saturation analysis techniques revealed a concentration gradient across the testis for both estrone and estradiol-17β as well as androstenedione (4-androstene-3, 7-dione) and testosterone. This shows that there is direct testicular secretion of estrone and estradiol-17β in normal young males and that this testicular secretion can be an important source of both steroids.

Estradiol-17β and estrone: Studies on their binding to rabbit uterine cytosol and their concentration in plasma

Abstract Studies have been carried out on the binding of 3H-estradiol and 3H-estrone to a soluble fraction of rabbit uterus. Dextrancoated charcoal has been used to separate the free and bound moieties at the end of the incubation. The binding of either 3H-estrogen was greater when the incubation was carried on at 4°C than at 24°C. The time needed to achieve the maximal binding, however, was greater at 4°C than at 24dgC. Dextran-coated charcoal removed the free steroid rapidly but the steroid-protein complex underwent minimal dissociation during 30 min of exposure to charcoal. Under the conditions employed, the assay itself had a sensitivity of 5 pg for both steroids. The mean concentrations of estradiol in the plasma of men aged 21–40 was 25.6 ±1.5 (SE) pg/ml, in men aged 70–90 years was 21.8 ±3.2 (SE) pg/ml and in post-menopausal women aged 70–90 years was 45 ± 1.0 (SE) p g/ml. The mean concentrations of estrone in males aged 21–40 years was 30.1 ± 3.8 (SE) pg/ml, in males aged 70–90 years was 43.0 ± 6.5 (SE) pg/ml and in post-menopausal women aged 70–90 years was 22.2 ± 41 (SE) pg/ml.

4-Hydroxyestrone: A new metabolite of estradiol-17β from humans☆

Abstract 4-Hydroxyestrone has been identified, by reverse isotope dilution, as a urinary metabolite after injection of a mixture of 4- 3 H- and 4- 14 C-estradiol-17β into a 23 year old woman and a 39 year old man. This new metabolite accounted for 1.1% of the - 14 C dose administered to the woman and 0.51% of the - 14 C dose administered to the man. 7.3% Of the 3 H dose was liberated into the body water pool of the woman and 6.1% into that of the man. The yields of radioactive estrone, estradiol-17β, estriol, 2-hydroxyestrone, 2-methoxyestrone and 2-hydroxyestrone 3-methyl ether were also measured in both the Ketodase and Glusulase hydrolyzed urinary fractions from both subjects.

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.