Estrogen and progesterone receptors are not increased in generalized essential telangiectasia.
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Adult↗
Biomedical subjects
C Longcope
Publications and source records attributed to C Longcope.
Male-limited familial precocious puberty in three generations. Apparent Leydig-cell autonomy and elevated glycoprotein hormone alpha subunit.
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Adrenocorticotropic Hormone↗
Effect of D-thyroxine on serum sex hormone binding globulin (SHBG), testosterone, and pituitary-thyroid function in euthyroid subjects.
Concentrations of serum sex hormone binding globulin (SHBG) and free testosterone (T) were examined in 10 euthyroid subjects (5 men and 5 women) before, during and after 30 days of the daily ingestion of 1 or 4 mg D-thyroxine (D-T4), the thyroxine analog that has only 1-15% of the calorigenic effect of L-thyroxine (L-T4). No changes in serum L-T4 or triiodothyronine (T3), serum cholesterol, SHBG, T, progesterone, estradiol-17 beta, or free T concentrations were observed in response to the 1 mg dose, but there was a slight elevation in the free thyroxine index (FTI) and a significant (p less than 0.02) suppression of the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH). The 4 mg dose of D-T4 induced an increase in SHBG levels in all but one man. There was a significant negative correlation between the SHBG and percent free T (p less than 0.05) although the mass of free T did not change. As a group, the women responded with a greater increase in SHBG and decrease in percent free T than the men. Serum cholesterol decreased (p less than 0.01), all serum thyroid hormone values measured by RIA were increased (p less than 0.01), and the TSH response to TRH was completely suppressed. Despite these changes, the subjects remained clinically euthyroid. Concentrations of testosterone, progesterone and estradiol-17 beta remained unchanged. Serum luteinizing hormone (LH), which was evaluated in the men only, also did not change during the daily administration of 4 mg D-T4.
Adult↗
Estrogen and androgen dynamics in liver disease.
Constant infusions of 3H-androgen/14C-estrogen were given to 18 men with increased serum bilirubin concentrations and biopsy proven hepatic cirrhosis. From data obtained from the infusions and the radioimmunoassay of circulating endogenous steroid levels metabolic clearance rates (MCR), blood production rates (PB), aromatization rates (fraction of androgen infused into and measured as estrogen in blood; [p]And, Est BB) and conversion ratios (ratio of concentration of radioactivity of infused precursor to product steroid in blood; CRPREC,PROD were calculated. These data were compared to normal data obtained from similar studies in a group of normal men similar in age and weight. The mean concentrations of testosterone (T), and dihydrotestosterone (DHT), were decreased but those of estrone (E1) and estradiol (E2) were increased, and the concentration of androstenedione, (A), was similar compared to the normal values. Compared to the values in normal men the mean MCR of T was decreased those of A and E2 were normal, and that of E1 was slightly increased. However, the PB's of both estrogens were increased while that of A was normal T was decreased. The increase in the PB's of the estrogens could be explained on the basis of a marked increase in [p]And, Est BB probably due to a shift in blood flow from the liver to peripheral tissue. These findings were noted in men with alcoholic cirrhosis as well as cardiac cirrhosis and in 1 subject with infectious hepatitis. Abnormalities in steroid metabolism occur in men with several types of liver disease and are not limited to those with alcoholic liver disease.
Adult↗
Estriol production and metabolism in normal women.
Studies on estriol metabolism and production were carried out in normal reproductive-aged and post-menopausal women using pulse injections and constant infusions of radiolabeled estriol, estrone and estradiol. The circulating levels were measured by radioimmunoassay. Following an intravenous pulse of [3H]estriol, the disappearance of radioactivity as estriol could be described as a function which was sum of two exponentials with t 1/2's of 3.6 and 64 min. The initial volume of distribution was 201. Using the constant infusion technique the metabolic clearance rate (MCR) of estriol was 2100 1/day in the follicular phase of the cycle and similar in the luteal phase. In postmenopausal women the MCR was 1890 1/day. The circulating levels of estriol were 7 and 11 pg/ml in the follicular and luteal phases respectively and 6 pg/ml in post-menopausal women. The production rates of estriol were 14 and 23 micrograms/day in the follicular and luteal phases of the cycle and 11 micrograms/day in post-menopausal women. In many of the women infused with radiolabeled estrone or estradiol, no radioactivity could be identified in the blood as estriol. The maximal conversion of estrone and estradiol was less than 0.4%. Estriol circulates at low but relatively steady levels in the blood. In some women estriol appears to be secreted by the ovary, especially in the luteal phase.
Adult↗
Steroid dynamics in the rabbit.
Male rabbits were infused at a constant rate with 3H-androstenedione/14C-estrone (n = 5) or 3H-testosterone/14C-estradiol-17 beta (n = 3) for 3 1/2 hr and blood samples were obtained over the last hour and analyzed for radioactivity as androstenedione (A), testosterone (T), estrone (E1), estradiol-17 beta (E2 beta) and estradiol-17 alpha (E2 alpha). The mean value for the metabolic clearance rate of androstenedione (MCRA) was 85 +/- 10 l/day/kg, which was significantly greater than the mean MCRE1 59 +/- 10 l/day/kg. MCRT, 42 +/- 8 l/day/kg, and MCRE2 beta, 45 +/- 9 l/day/kg were not different. The conversion ratio of androstenedione to testosterone (CRA,T) was greater than CRT,A but for the estrogens, CRE2 beta, E1 was greater than CRE1,E2 beta. CRE2 beta, E2 alpha was greater than CRE1,E2 alpha. The overall aromatization of androstenedione to estrone, the fraction of 3H-androstenedione infused into the blood and measured as 3H-estrone in blood [( rho]A,E1BB) was 0.0005 +/- 0.0001 and for [rho]T,E2 beta BB was 0.0012 +/- 0.0006. In the rabbit both sex hormone binding globulin (SHBG) and albumin binding may effect the MCRs, and peripheral aromatization of androgens occurs to a far lesser degree than in humans and primates.
Androstenedione↗
Androgen and estrogen dynamics in women with vertebral crush fractures.
Using constant infusions of [3H]androgen/[14C]estrogen we measured metabolic clearance and production rates and aromatization of androgens to estrogens in post-menopausal women with vertebral crush fractures and compared these results to similar measurements in a similar population of post-menopausal women who did not have vertebral crush fractures. The mean +/- SEM values for the metabolic clearance rates of testosterone and estrone, 220 +/- 10 and 880 +/- 50 1/day per m2, were significantly less in the crush fracture group than the respective mean values in the control group, 280 +/- 15 and 1110 +/- 70 1/day per m2. The mean concentration of estradiol was higher in the crush fracture group, 18 +/- 2 pg/ml, compared to that in the control group, 13 +/- 1 pg/ml. However, for the crush fracture group the mean blood production rates of both androstenedione, 0.7 +/- 0.1 mg/day, and testosterone, 56 +/- 9 micrograms/day, were significantly less than the respective values in the control group, 1.2 +/- 0.2 mg/day and 115 +/- 15 micrograms/day. The production rates for estrone and estradiol were not different for the two groups. In addition the mean value for the fraction of adrostenedione converted to testosterone ( [rho]A, T BB) was lower in the crush fracture, 0.030 +/- 0.002 compared to the control group, 0.041 +/- 0.004. Thus the amount of biologically available androgen is less in the vertebral crush fracture group than in the control group. However, since these measurements represent an isolated point temporally removed from major changes in bone morphology, their exact relationship to the crush fracture and osteoporotic process remains uncertain.
Androgens↗
Becker's nevus: an androgen-mediated hyperplasia with increased androgen receptors.
Becker's nevus is an uncommon, unilateral, hyperpigmented, hairy cutaneous hamartoma which usually begins in adolescence. Its clinical features and its occurrence mainly in male individuals suggest that androgen stimulation may play a role in its pathogenesis. Androgen receptor assays were performed in a 16-year-old patient with a Becker's nevus. The patient coincidentally had acanthosis nigricans. Lesional tissue showed an androgen receptor level of 634.1 fm/mg protein. A specimen from the contralateral left pectoral area showed no dectectable androgen receptor activity (less than 2.0 fm/mg protein). These results suggest that exquisite androgen sensitivity and stimulation may explain the clinical manifestations of Becker's nevus.
Acanthosis Nigricans↗
A zonal pattern of cell proliferation and differentiation in the rhesus endometrium during the estrogen surge.
The cellular and tissue basis of endometrial renewal in the rhesus monkey is being investigated by radioautographic localization of proliferating cell populations. Here we report our findings on epithelial cell proliferation during the midcycle estrogen surge. Endometrial biopsies were obtained by hysterotomy at approximately 1 h after a single intravascular injection of [3H] thymidine ([3H]T). Light and electron microscopic radioautography was performed on 7 specimens obtained from 4 monkeys in relation to the serum estradiol (E2) peak as follows: -2, -1, 0, +1, +2, and +3 days (+/- 1 day). Cell proliferation and differentiation were analyzed according to the 4 horizontal histologic endometrial zones (Bartelmez et al., 1951). Epithelial labeling indices were higher in the functionalis (Zone I, luminal epithelium, 9-12%; Zone II, uppermost gland segments, 7-14%) than in the basalis (Zone III, middle gland segments, 5-7%; and Zone IV, basal gland segments, 1-7%). Despite the large and rapid serum E2 fluctuations during the surge from -2 days to +3 days E2 peak, proliferating epithelial populations within Zones I, II and III remained quite uniform in size. In the basalis, the proliferative patterns of Zones III and IV were dissimilar. The labeling index of Zone III remained quite uniform (5-7%), whereas in Zone IV, it increased progressively from 1% (-2 days) to 7% (+3 days). These data establish the bipartite nature of the basalis. Radioautographic evidence indicates that endometrial cell proliferation is tightly coupled to progressive cell differentiation in the functionalis and basalis. Thus intrinsic positional differences exist in the responsiveness of the primate endometrium to common hormonal stimulation during the E2 surge and the initial postovulatory rise of progesterone.
Animals↗
The rat LTW(m) Leydig cell tumor: cancer anorexia due to estrogen.
Anorexia occurs in male rats bearing transplantable LTW(m) Leydig cell tumors. Previous studies had shown that this tumor caused decreased food consumption and weight loss within 2 weeks of implantation. Additional studies reported here demonstrate that this tumor had little anorectic effect in female rats, and that male rats with LTW(m) tumors had elevated concentrations of circulating estradiol and low levels of testosterone. The tumor was also anorexigenic in castrated male rats. Exogenous estrogen given in the form of sc implanted pellets of estradiol reduced weight gain in male rats in proportion to the dose of estradiol. Weight gain was reduced when the plasma estradiol concentration was as low as 49 +/- 3 pg/ml; control estradiol levels were 25 +/- 4 pg/ml. Similar effects were observed in male Zucker fatty rats. It was further demonstrated that the tumor is anorexigenic in ventromedial hypothalamus-lesioned rats, an effect previously observed in ventromedial hypothalamus-lesioned rats given exogenous estradiol. Carcass analysis revealed that tumor-bearing rats used a metabolic fuel mixture containing a higher percentage of fat-derived substrates compared to nonimplanted controls, suggesting that altered fuel utilization may contribute to the decreased weight gain of tumor-bearing rats. We conclude that the circulating substance responsible for LTW(m) tumor-induced anorexia in male rats is likely to be an estrogenic steroid.
Animals↗
The effect of D- and L-thyroxine on sex hormone-binding globulin in rabbits.
Serum sex hormone-binding globulin (SHBG) concentration is increased in patients with thyrotoxicosis. SHBG is also present in rabbit serum, although it does not bind estradiol-17 beta (E2). Studies were carried out in female rabbits to determine the effects of thyroid hormone on SHBG. Serum concentrations of L-T4 cholesterol, E2, progesterone, free and total testosterone (T), and SHBG were measured in immature female rabbits (8-10 weeks of age). Rabbits were ovariectomized or subjected to sham surgery at puberty (age, 14-16 weeks) and restudied 6 weeks later. Values for serum T4, T, percent free T, free T, E2, progesterone and cholesterol were similar in ovariectomized and sham treated rabbits. Serum SHBG concentration progressively decreased in all rabbits from immaturity to age 20-22 weeks and values remained constant thereafter. Ovariectomy did not affect this age-related decrease in serum SHBG concentration. The 20- to 22-week-old ovariectomized and sham-operated rabbits were treated daily with either 30 micrograms/kg L-T4 or 150 micrograms/kg D-T4 for 2 weeks. This dose of L-T4 induced a 10-25% loss of BW, whereas D-T4 treatment did not, strongly suggesting that the L-T4 but not the D-T4-treated rabbits were hypermetabolic. D-T4 and L-T4 induced similar increases in serum SHBG (D-T4, delta 132 nM; L-T4, delta 146 nM). The increase in serum SHBG activity in response to D-T4 or L-T4 was reversible, since serum SHBG concentration returned to pretreatment values 5 weeks after thyroid hormone therapy was discontinued. The 27- to 29-week-old rabbits were then treated for 2 weeks with D-T4 (150 micrograms kg-1 day-1). Serum SHBG concentration significantly increased, and there were negative correlations between the thyroid hormone-induced increase in SHBG activity and both the percent free T and free T (P less than 0.01). D-T4 administration significantly lowered the serum cholesterol concentration without altering BW.
Animals↗
Aromatization by splanchnic tissue in men.
To measure the rate of aromatization that occurs in splanchnic tissue, four men with normal liver function were infused through an arm vein with [3H]androstenedione/[14C] estrone and four men were infused with [3H]testosterone/[14C] estradiol before indicated cardiac procedures. Catheters were placed under fluoroscopic control in the hepatic vein and descending aorta. Simultaneous blood samples were then obtained from the aorta and the hepatic vein after 90 and 120 min of infusion. The samples were analyzed for radioactivity after multiple chromatographic purification steps. The MCRs, overall aromatization (fraction of androgen infused measured as estrogen in arterial blood), splanchnic extractions, and splanchnic aromatization (fraction of androgen entering the splanchnic tissue which leaves as estrogen) were determined. The mean values for MCRs of androgens and estrogens and overall aromatization for androstenedione and testosterone were similar to those reported previously. The splanchnic extraction values of androstenedione, testosterone, estrone, and estradiol were 0.57 +/- 0.10 (+/- SE), 0.39 +/- 0.12, 0.60 +/- 0.09, and 0.64 +/- 0.18, respectively. The mean splanchnic aromatization of androstenedione to estrone was 0.00086 +/- 0.00072, and the mean splanchnic aromatization of testosterone to estradiol was 0.00059 +/- 0.00020. If one assumes that the splanchnic bed receives 20% of the cardiac output, then the splanchnic bed is responsible for less than 4% of the overall peripheral aromatization of androstenedione or testosterone.
Androgens↗
Biological activities of 4-fluoro estrogen analogues.
As part of a study on the biological activity of gamma-emitting estradiol analogues, a series of fluorinated and/or brominated analogues of estradiol were synthesized. 4-Fluoro-1,3,5(10-estratrien-3,17 beta-diol (4-fluoro-estradiol) and 16 alpha-bromo-1,3,5(10)-estratrien-3,17 beta-diol (16 alpha-bromo-estradiol) had relative binding affinities (RBA) for the rabbit uterine cytosol receptor which were comparable to those of estradiol. However, while 4-fluoro-estradiol stimulated the increase in uterine weight of immature mice to the same amount as estradiol, 16 alpha-bromo-estradiol was less effective in this assay indicating that its metabolism is probably more rapid than that of estradiol. 16 beta-Bromo-1,3,5(10)-estratrien-3,17 beta-diol had a low RBA and was ineffective in stimulating uterine weight at the doses used. 4-Fluoro-16 alpha-bromo-estradiol had a lower RBA than either the 4-fluoro- or 16 alpha-bromo-estradiol and all the 4-fluoro-seleno-estrogens tested possessed low RBA's.
Animals↗
Tissue sites of aromatization in the female rhesus monkey.
Nine female rhesus monkeys (four in the follicular and five in the luteal phases of their cycles) had catheters implanted and were infused iv with [7-3H]androstenedione (A) and [4-14C]estrone (E1) for 4 h. Blood samples were drawn at intervals from the hepatic, renal, jugular, uterine, and brachial veins and the femoral artery. The samples were analyzed for radioactivity as A and E1. The mean +/- SE MCRs for A and E1 were 280 +/- 40 and 270 +/- 30 liters/day, respectively. The mean extractions across the liver measured in six of the monkeys were 0.83 +/- 0.03 for A and 0.71 +/- 0.06 for E1. The percentage of A entering each tissue, which was measured as E1 leaving the tissue (pA,E1AV), was 0.20 +/- 0.10 for splanchnic, 0.21 +/- 0.11 for renal, 0.46 +/- 0.21 for jugular, 2.36 +/- 1.27 for arm, and 0.35 +/- 0.10 for uterine veins. Because of the sampling technique, the value for the uterus may be a reflection of ovarian blood admixture with uterine blood. There were no apparent differences in tissue aromatization between values in the follicular and luteal phases of the cycle. The overall mean value for the percentage of A infused and measured as E1 in arterial blood (pA,E1BB) was 1.01 +/- 0.38%. Using previously reported tissue blood flow, we calculate that the contributions to the overall aromatization rate of tissues drained by the brachial, renal, jugular, hepatic, and uterine veins are 23%, 5%, 5%, 4%, and 0.2%, respectively. Thus, the splanchnic tissue is a minor site for extraglandular aromatization of androgens in the rhesus monkey. An important site appears to be the arm, which reflects aromatization in adipose tissue, muscle, skin, and supporting structures.
Androstenedione↗
Metabolism of 2-methoxyestrone in normal men.
We studied, in four normal men, the metabolism of 2-methoxyestrone (2-MeOE1) using pulse injections of either [3H]2MeOE1 (two men) or [14C]methoxy-2-MeOE1 plus [3H]2-MeOE1 (two men) by analysis of blood samples drawn at increasing time intervals after the pulse and of urine collected for 5 days. The disappearance from the blood of radioactivity as 2-MeOE1 could be characterized as a function that was the sum of three exponentials. The mean +/- SE value for the initial volume of distribution was 32 +/- 9 liters, and the mean MCR was 2470 +/- 770 liters/day. The disappearance of total 3H radioactivity from the blood was considerably slower, with a mean MCR of 290 +/- 30 liters/day, indicating the presence of a slowly turning over pool of 2-MeOE1 metabolites, probably including the 2-MeOE1 3-sulfate conjugate. The disappearance of total 14C radioactivity was slower than that of total 3H, indicating considerable demethylation of 2-MeOE1 with a very slow excretion of 14C from the released methyl group. In none of the subjects could we find in the blood radioactivity as unconjugated [3H]2-hydroxyestrone ( [3H]2-OHE1). However, examination of the urine indicated that considerable demethylation of [3H]2-MeOE1 had occurred. At least 64% of the urinary 3H-containing metabolites from the mixed dose had lost the 14C-bearing methoxylcarbon atom. The fractionated metabolites were qualitatively and quantitatively similar to those found earlier for [3H]2-OHE1. We conclude that 2-MeOE1, which of itself has little biological activity, can act as a pool of potentially active 2-OHE1 in the tissues.
Adult↗
The production and aromatization of dehydroepiandrosterone in post-menopausal women.
Using infusions of [3H]dehydroepiandrosterone (DHEA) and [14C]oestrogens, the metabolic clearance rates (MCRD) and blood production rates (PDB) of DHEA and the rate of aromatization of DHEA to oestrone and oestradiol were measured in 7 normal post-menopausal women. The mean +/- SEM value for MCRD was 1850 +/- 270 l/day and for PDB was 3.2 +/- 0.6 mg/day. The MCRD value is similar to those reported for young women but PDB is less than those reported for younger women. The mean +/- SEM value for the aromatization rate of DHEA to E1 in 6 women was 0.0058 +/- 0.004 and in 1 woman the aromatization rate of DHEA to E2 was 0.0008. About 30% of the aromatization of DHEA to E1 occurred via the blood pool of androstenedione. However, 20-25% of E1 arose via the aromatization of DHEA to E1 in peripheral tissues without the intermediacy of the blood pool of androstenedione, and thus the peripheral aromatization of DHEA can be an important source of E1 in some women.
Aged↗
The biologic activity of selenoestrogens.
For differential imaging of mammary tumors with estrogen receptors and without estrogen receptors we required gamma-emitting estrogen analogues. In this paper we report on the binding properties of 7 alpha-, 16 alpha-, and 17 alpha-methylselenoestrogens and 17 alpha-phenylselenoestrogens relative to the binding properties of estradiol. The selenium-containing estrogens retained the ability to displace [3H]estradiol from the estrogen receptor of rabbit uterine cytosol, although in most instances the displacement was small (3-7% compared to estradiol). The most active compounds were 16 alpha-phenylselenoestrone, 16 alpha-methylselenoestradiol, and 17 alpha-methylselenomethyl-estradiol which had relative binding of 23, 27, and 31%, respectively, compared with that of estradiol. 16 alpha-Methylselenoestradiol was able to translocate the estrogen cytosol receptor to the nucleus, in vitro, but was not able to increase the uterine weight when administered to mice in vivo.
Animals↗
Serum testosterone and gonadotropins in the genetically obese male Zucker rat.
Serum concentrations of testosterone, LH, and FSH were measured in obese and lean male Zucker rats 1--6 months of age. The serum concentrations of testosterone were lower in the 2-, 3-, and 4-month-old obese rats than in their lean controls. There was no correlation between fertility and serum testosterone concentration in the obese ras. Serum LH and FSH concentrations were normal, as was the response of the obese rats to LHRH stimulation. Testes morphology differed between the obese and the lean rats. Although the Leydig cells of the obese rat testes were hypertrophied, they contained numerous fat droplets and few signs of active hormone synthesis. These data suggest that the obese male Zucker rat has a defect in testicular testosterone production but has a normal pituitary response to hypothalamic stimulation.
Animals↗