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C Longcope

Publications and source records attributed to C Longcope.

At least 109 records · Page 6Linked to original sources
PubMed1989

The questionable physiologic and epidemiologic basis for a male climacteric syndrome: preliminary results from the Massachusetts Male Aging Study.

This paper examines the physiologic and epidemiologic evidence for a widely discussed syndrome termed either 'mid-life crisis', 'male menopause', 'male climacteric', or increasingly, 'andropause'. The paper is divided into 2 parts: (1) a review of evidence from physiologic studies conducted over the last decade that examine endocrine function in aging males; (2) a description of the salient features of an ongoing multidisciplinary epidemiologic study (the Massachusetts Male Aging Study) of a sample of approximately 1700 men aged 40-69 yr, randomly sampled from the general population. This study is markedly different in size and content from studies conducted to date. Preliminary findings suggest that age per se may be a relatively unimportant contributor to endocrine variability and that anthropometrics and life style phenomena may be at least as important.

Adult↗
PubMed1989

The effect of ovariectomy on spine bone mineral density in rhesus monkeys.

As part of a study on the effects of hormones on uterine biology and estrogen metabolism, 12 normal female rhesus (Macaca mulatta) monkeys were ovariectomized, and treated intermittently with estradiol and progesterone. In order to determine whether there were changes in bone density as a result of ovariectomy despite the hormone therapy, spine bone mineral density (BMD) was measured by dual-photon absorptiometry. The mean +/- SE time from ovariectomy was 26 +/- 3 months, the mean estrogen treatment time was 3.5 +/- 0.4 months and the mean time from last hormonal treatment was 4.1 +/- 0.6 months. In these 12 monkeys aged 7.7 +/- 0.2 years, the mean spine BMD, 0.825 +/- 0.008 g/cm2, was significantly less, p = 0.0011, than the spine BMD, 0.863 +/- 0.007 g/cm2, in 12 intact female rhesus of similar age, 7.6 +/- 0.1 years and weight. Ovariectomy in female rhesus monkeys results in a relatively rapid diminution of spine BMD which is not prevented by intermittent hormonal replacement. This species may be an excellent model for studies of human osteoporosis.

Absorptiometry, Photon↗
PubMed1989

Low-fat, high-fiber diet and serum estrone sulfate in premenopausal women.

The effect of diet on serum estrogen levels was investigated in 17 healthy premenopausal women consuming defined diets prepared in a metabolic unit. During an initial 4-wk control period all women consumed a typical Western diet (40% of total calories from fat, 400 mg cholesterol/d, 12 g dietary fiber/d, and a ratio of polyunsaturated to saturated fatty acids [P:S] of 0.5). After this control period they were switched to a low-fat, high-fiber diet for 8-10 wk, which consisted of 25% of calories from fat, P:S of 1.0, cholesterol of 200 mg cholesterol/d, and 40 g dietary fiber/d. Compared with the control period 16 of 17 women had lower serum estrone sulfate levels on the low-fat, high-fiber diet. There was an average decrease of 36% with mean levels decreasing from 2.11 +/- 0.25 nmol/L (means +/- SEM) on the control diet to 1.29 +/- 0.19 nmol/L on the experimental diet (p less than 0.001). We conclude that a low-fat, high-fiber diet can significantly reduce serum estrone sulfate levels.

Adult↗
PubMed1989

The basalis of the primate endometrium: a bifunctional germinal compartment.

Radioautographic analysis of epithelial and stromal cell proliferation in the primate endometrial functionalis and basalis (rhesus monkey) has identified horizontal zonal patterns of mitotic activation and inhibition during natural menstrual cycles. At 1 h after a single i.v. injection of [3H]thymidine, mitotic activity in endometrial biopsies (hysterotomy) was determined on 9 days from the late proliferative to the late luteal phase (-2 days to + 14 days relative to the estrogen [E2]peak). Labeling indices (LIs) were determined within glandular segments of the 4 horizontal endometrial zones: Transient functionalis Zone I (luminal epithelium) and Zone II (uppermost gland); Germinal basalis: Zone III (middle gland) and Zone IV (basal gland). The size of the dividing epithelial populations (LI) differed zonally. During E2 dominance (-2 days to +3 days), the epithelial LIs of functionalis I (10 +/- 0.3%) and II (9.8 +/- 1.0%) were greater than those of basalis III (5.8 +/- 0.2%) and basalis IV (3.7 +/- 0.8%). During progesterone (P) dominance (+5 days to +14 days), epithelial mitosis was strongly inhibited in functionalis I (4.3 +/- 1.9%), functionalis II (0.8 +/- 0.2%), and basalis III (1.4 +/- 0.5%). Thus germinal basalis III was linked functionally with transient functionalis I and II by periovulatory uniformity in epithelial proliferation and postovulatory mitotic inhibition. A unique mitotic pattern set basalis IV apart from other zones by a steady rise in LI from 1% (-2 days) to 11% (+10 days). The LIs for stromal fibroblasts remained quite uniform in basalis IV but varied in other zones. Thus the postovulatory primate basalis was a distinct bipartite compartment in which the mitotic rate in basalis IV glandular epithelium increased steadily whereas that of basalis III was strongly inhibited. The remarkable enhancement of epithelial mitotic activity in basalis IV may reflect expansion of the stem-progenitor cell population for gestational growth or for post-menstrual regeneration.

Animals↗
PubMed1989

Estrogen interconversions in the induced cycle in female rhesus monkeys.

To determine the extractions and interconversions of estrone and estradiol across and within the uterus, [3H]estradiol and [14C]estrone were infused at a constant rate in six ovariectomized female rhesus (Macaca mulatta) monkeys. Studies were done on Days 9, 14, and 23 of artificial menstrual cycles induced by the timed insertion and removal of Silastic capsules of estradiol and progesterone. Measurements of estrogen radioactivity were made from peripheral arterial blood and uterine venous blood as well as from endometrial biopsy samples. A significant increase occurred in the conversion of estradiol to estrone measured within the uterus on Day 23 compared to Days 9 and 14. The conversion of estrone to estradiol, measured within the uterus, fell progressively from Day 9 to Day 23, but this decrease was not significant. The extractions and interconversions across the uterus, and the overall interconversions of estrone and estradiol were not significantly different on Days 9, 14, or 23 of the cycle. Thus, we have been able to confirm in vivo the increase in the activity of the 17 beta-hydroxysteroid dehydrogenase, the enzyme responsible for estradiol to estrone interconversions, shown earlier by studies done in vitro. However, the increase in 17 beta-hydroxysteroid activity in the uterus is not reflected in the overall interconversions of estrone and estradiol as reflected by measurements in peripheral arterial blood.

17-Hydroxysteroid Dehydrogenases↗
PubMed1989

Immunofluorescent analysis of estrogen induction of progesterone receptor in the rhesus uterus.

Estrogen (E) has been shown to induce an increase in progesterone (P) receptor (PR) concentration in uterine tissue of both rodents and primates. Because of the presence of different cell types within the uterus, we were interested in determining whether estrogen-induced PR were cell type specific in the nonhuman primate uterus (rhesus monkey). Immunofluorescent analyses of E receptor (ER) and PR were performed on fresh frozen cryostat sections (6 microns) of uterine tissue from ovariectomized (3 months) and estradiol (E2)-treated (peak level of E2 during an artificial menstrual cycle) rhesus monkeys. Antibodies to ER and PR were obtained from Abbott Laboratories (H222) and Transbio (MPR1). The avidin-biotin complex technique was used with streptavidin-conjugated Texas red for fluorescent detection. Ovariectomized monkeys showed positive fluorescence for ER in luminal and glandular epithelia, stromal cells, and smooth muscle cells of the myometrium. In contrast, positive fluorescence for PR was observed primarily in glandular epithelia, with little or no fluorescent detection in luminal epithelium, stromal cells, or myometrial smooth muscle cells. After E2 treatment strong positive fluorescence for PR was observed in luminal and glandular epithelia, stromal cells, and myometrial smooth muscle cells. Strong positive fluorescence for ER was also observed in the same cell types. Fluorescent detection of ER and PR was restricted to the nuclei of these cell types. These studies show that ER are present constitutively in all cell types of the E-withdrawn (ovariectomized) nonhuman primate uterus, whereas PR are primarily restricted to glandular epithelia. E2 treatment, which simulated the follicular phase and E2 surge, resulted in the appearance of immunofluorescent PR in luminal epithelia, stromal cells, and myometrial smooth muscle cells. These studies serve to define the cellular pattern of E2-induced PR in the primate uterus.

Animals↗
PubMed1989

Metabolic clearance rate (MCR) of dehydroepiandrosterone sulfate (DS), its metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone, and the effect of increased plasma DS concentration on DS MCR in normal women.

The combined infusion of [3H]dehydroepiandrosterone sulfate [( 3H]DS) and [14C]estrone (E1) for 6 h in four normal women in the follicular phase of the cycle demonstrated values of 13.77 +/- 0.27 L/day (mean +/- SE) for the DS MCR (MCRDS) and 1343 +/- 206 L/day for MCRE1. The fraction of DS metabolized to dehydroepiandrosterone (D), [rho]DS-D, was 0.285 +/- 0.044, and the fraction of D arising from DS (delta D) was 0.318 +/- 0.096, determined using isotopic techniques. Raising the plasma DS concentration by 8.6 micrograms/mL (23 mumol/L) by infusing DS iv increased the MCRDS to 24.49 L/day in the first subject, and raising the plasma DS by 11.40 +/- 0.33 micrograms/mL (30.94 +/- 0.90 mumol/L) in the next three subjects raised the MCRDS to 35.7 +/- 1.3 L/day (P less than 0.01) without changing the MCRE1. The increase in MCRDS produced by increasing plasma DS makes it difficult to accurately measure the MCRDS in effect at the subject's endogenous plasma DS concentration by infusion of nonisotopic DS. Determination of the fractions of D, androstenedione (delta delta 4A), and testosterone (T) arising from DS using the increase in the plasma concentrations of these steroids produced by infusion of nonisotopic DS gave the following estimates: delta D = 0.262 +/- 0.042, delta delta 4A = 0.089 +/- 0.046, and delta T = 0.273 +/- 0.14.

Adult↗
PubMed1988

Androgen and estrogen dynamics in the female baboon (Papio anubis).

Androgen and estrogen dynamics were studied in 5 female baboons (Papio anubis) using constant infusions of [3H]androstenedione/[14C]estrone and [3H]testosterone/[14C]estradiol. Blood samples were obtained prior to the infusions and both blood and plasma was used for measurements of androstenedione (A), testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2). Plasma was used for measurements of sex-hormone binding globulin (SHBG), and the percents of T and E2 free, bound to SHBG, and to albumin. Blood samples obtained during the infusions were analyzed for radioactivity as purified androgens and estrogens. Metabolic clearance rates (MCR), and transfer factors ([rho]BB; fraction of steroid infused which is converted to and measured in blood as product) and blood production rates were calculated from whole blood data. All urine was collected for 96 h and an aliquot analyzed for radioactivity as the glucuronides of estrone and estradiol and the % peripheral aromatization calculated. The MCR's, calculated in whole blood, of A, E1, E2 and T were 53 +/- 6 1/day/kg, 39.3 +/- 3 1/day/kg, 29.9 +/- 5.2 1/day/kg and 10.1 +/- 2.3 1/day/kg, respectively. Each MCR was different (P less than 0.05) from the others. The PB of E1 was 15 +/- 2 micrograms/day and was not different from that of E2 (12 +/- 3 micrograms/day). The PB of A, 231 +/- 55 micrograms/day, was greater than that of T, 13 +/- 5 micrograms/day. The interconversions of both the androgens (18.9 +/- 3.4% vs 3.9 +/- 1.0%) and the estrogens (48.8 +/- 10.7% vs 4.0 +/- 0.8%) favored the oxidative pathway, i.e. conversion of 17-OH to 17-oxo steroids. The conversion ratio of A to DHT was greater than that of T to DHT (16.4 +/- 2.1% vs 5.3 +/- 0.7%), and A is a more important source of DHT than is T. The percent of T bound to SHBG (80.7 +/- 0.9%) was greater than percent of E2 (36.9 +/- 9.8%) and inversely the percents of T bound to albumin and free (17.5 +/- 0.8% and 1.65 +/- 0.16%) were less than the respective percents for estradiol (60.5 +/- 9.5% and 2.40 +/- 0.27%). The mean SHBG concentration was 54 +/- 6 nM. The peripheral aromatization of androstenedione, 1.36 +/- 0.05%, was greater than of testosterone, 0.18 +/- 0.02%. This difference is, in part, due to the lack of SHBG-binding of androstenedione. The general pattern of androgen and estrogen dynamics is similar to that in women. This similarity is due, in part, to the presence of SHBG in both baboons and women.

Androgens↗
PubMed1988

Estrogen dynamics in the female rhesus monkey.

The metabolic clearance rates (MCR) and interconversions [( rho]BB) values for estrone (E1) and estradiol (E2) in female rhesus (Macaca mulatta) monkeys on Days 9, 14, and 23 of the menstrual cycle were measured using constant infusions of [3H] estradiol and [14C] estrone. The menstrual cycles in these monkeys were reproduced by using Silastic capsules of E2 and progesterone after bilateral ovariectomy. The serum levels of E2 and progesterone were measured by radioimmunoassay and were similar to those for the intact menstrual cycle. The MCR of E2 on Day 14 (52.8 +/- 6.8 l/day/kg) was significantly greater (p less than 0.05) than that measured on Day 9 (31.1 +/- 3.6 l/day/kg) or Day 23 (35.4 +/- 2.1 l/day/kg). The MCR of E1 was also different (p less than 0.05) on Day 14 (77.6 +/- 14.9 l/day/kg) compared to the values on Days 9 and 23 (50.2 +/- 4.9 and 48.2 +/- 3.9 l/day/kg, respectively. There was no change in percentage of free E2, percentage of albumin-bound E2, or sex hormone-binding globulin levels on those 3 days of the cycle. The interconversions between E2 and E1 were not influenced by the day of the cycle. We conclude that the high levels of E2 occurring at the time of the E2 peak result in increases in the MCRs of both E2 and E1 that are not associated with changes in the pattern of protein-binding or in the activity of the 17 beta-hydroxy steroid dehydrogenase.

Animals↗
PubMed1988

Estrogen and androgen dynamics in the cynomolgus monkey.

We studied the dynamics of androgen, estrogen, and cortisol (F) production, metabolism, and protein binding in cynomolgus monkeys (M. fascicularis) to provide baseline data and to compare these parameters with those obtained in other primates. Constant infusions of 3H-labeled androgens, 14C-labeled estrogens, and [3H]F were administered to 11 male cynomolgus monkeys (M. fascicularis) for 3.5 h. Blood samples were obtained from a peripheral vein during the infusion, and all urine was collected for 96 h. In each of 3 monkeys, a catheter was inserted into the hepatic vein, and during the infusions blood samples were obtained from the hepatic and peripheral veins and the femoral artery. All blood and urine samples were analyzed for radioactivity as testosterone (T), androstenedione (A), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1). When indicated, blood samples were also analyzed for radioactivity as F. Blood samples taken before the infusions were analyzed for endogenous T, A, DHT, E1, E2, and F concentrations; percent free T, free E2, and free F; and sex hormone-binding globulin and F-binding globulin capacities. The mean +/- SE MCRs for T, A, E2, E1, and F were 44 +/- 4, 407 +/- 40, 175 +/- 17, 315 +/- 28, and 57 +/- 6 liters/day, respectively. The mean blood production rates were 128 +/- 19, 91 +/- 14, 3.3 +/- 0.5, and 9.2 +/- 1.1 micrograms/day and 13.4 +/- 1.9 mg/day for T, A, E2, E1, and F, respectively. The aromatization of androgens was 1.30 +/- 0.10% for A to E1 and 0.28 +/- 0.03% for T to E2. The percent free F (4.34 +/- 0.42%) was greater than the percent free T (1.73 +/- 0.16%) or free E2 (2.75 +/- 0.22%), and the concentration of F-binding globulin was greater than that of sex hormone-binding globulin (227 +/- 35 vs. 60 +/- 7 nM). In the three monkeys who had hepatic venous catheterization, the mean extraction, across the splanchnic bed of T was 32 +/- 3%, that of E was 62 +/- 2%, and that of cortisol was 12 +/- 5%. Across peripheral tissues (leg) the mean extractions were 13 +/- 1%, 18 +/- 1%, and 6 +/- 4%, respectively. In general, the dynamics of androgen, estrogen, and F production and metabolism are similar in male cynomolgus and rhesus monkeys and in man. The similarity is especially close for peripheral aromatization despite differences in adipose tissue content between man and nonhuman primates.

Androstenedione↗
PubMed1988

Inhibition of peripheral aromatization in baboons by an enzyme-activated aromatase inhibitor (MDL 18,962).

The peripheral aromatization ([rho]BM) of androstenedione (A) and testosterone (T) was measured before and after administration of the aromatase inhibitor 10-(2 propynyl)estr-4-ene-3,17-dione (MDL-18,962) to five mature female baboons, Papio annubis. The measurements were made by infusing [3H]androstenedione/[14C]estrone or [3H]testosterone/[14C]estradiol for 3.5 h and collecting blood samples during the infusions and all urine for 96 h from the start of the infusion. Blood samples were analyzed for radioactivity as infused and product steroids, and the data were used to calculate MCRs. An aliquot of the pooled urine was analyzed for the glucuronides of estrone and estradiol and used to calculate the [rho]BM. MDL-18,962 was administered as a pulse in polyethylene glycol-400 (1-5 ml) either iv or via gastric tube 30 min before administration of the radiolabeled steroids. Control studies were done with and without polyethylene glycol-400 administration. When MDL-18,962 was given iv at 4 mg/kg, the aromatization of A was decreased 91.8 +/- 0.9% from the control value of 1.23 +/- 0.13% to 0.11 +/- 0.01%. At the same dose, aromatization of T was decreased 82.0 +/- 7.1%, from a control value of 0.20 +/- 0.03% to 0.037 +/- 0.018%. When MDL-18,962 was given iv at doses of 0.4, 0.1, 0.04, and 0.01 mg/kg, the values for aromatization of A were 0.16 +/- 0.03%, 0.18 +/- 0.06%, 0.37 +/- 11%, and 0.65 +/- 0.09%, respectively. The administration of MDL-18,962 via gastric tube at 4 mg/kg as a pulse decreased the aromatization of A from 1.35 +/- 0.06% to 0.43 +/- 0.12%, an inhibition of 67.2 +/- 10.7%. When administered via gastric tube daily for 5 days at 4 mg/kg, the aromatization of A fell from 1.35 +/- 0.06% to 0.063 +/- 0.003%, an inhibition of 84.4 +/- 0.5%. The MCRs of A and estrone were not altered by any dose of MDL-18,962 regardless of the mode of administration, but there was an increase in the MCRs of T and estradiol at the only dose (4 mg/kg, iv) at which these steroids were infused. The interconversions between the androgens and between the estrogens were not altered by the administration of MDL-18,962 at 4 mg/kg, iv. The enzyme-activated inhibitor MDL-18,962 is an effective inhibitor of [rho BM] in female baboons and could prove to be a useful therapeutic agent in treating estrogen-dependent breast cancer.

Androstenedione↗
PubMed1988

Androgen and estrogen dynamics in pre- and postmenopausal women: a comparison between smokers and nonsmokers.

To determine whether smoking affects androgen and estrogen production and metabolism we measured the MCRs, production rates (PB), androgen and estrogen interconversions, and percent peripheral aromatization in 88 pre- and postmenopausal women grouped as smokers or nonsmokers. These women were participating in an on-going study to determine the relationship between androgen and estrogen dynamics and osteoporosis. The dynamic measurements were done using constant infusions of [3H] androgen and [14C]estrogen, and the plasma steroid concentrations were measured by RIA. We found that women who were smokers had lower MCRs for androstenedione (A), testosterone, estrone, and estradiol than those who were nonsmokers, but when the data were adjusted for body weight, the MCRs were not significantly different for any of the steroids between smokers and nonsmokers. The mean plasma A concentration was higher in the smokers than in the nonsmokers but plasma testosterone, estrone, and estradiol concentrations were not different. The PB values for all steroids, the interconversions of the androgens and the estrogens, and the peripheral aromatization of the androgens were not different in the 2 groups. These results indicate that smoking does not alter the production and metabolism of androgens and estrogens in pre- and postmenopausal women. However, because the women who smoked were less heavy than those who were nonsmokers, their androgen and estrogen MCRs were lower, leading to a greater plasma A concentration. Our data do not rule out an effect of smoking on other specific pathways of estrogen metabolism.

Androgens↗
PubMed1987

Steroid hormone receptors in carcinoma of the cervix.

To correlate the presence of specific steroid receptors with certain characteristics of cervical carcinoma, cytosol estrogen receptors (ERc) were measured in 70 cases of cervical carcinoma, and progesterone receptors (PRc) were measured in 56 of these cases; ERc and PRc were also measured in 17 normal cervices. Measurements were made using a dextran-coated charcoal technique involving a seven-point Scatchard plot analysis. In carcinoma of the cervix significant numbers of ERc (greater than 3 fmol/mg protein) were found in 41% of the cases, and of PRc (greater than 3 fmol/mg protein) in 30%; only 28% of the 56 cases contained both ERc and PRc. In the normal cervices, 59% contained significant levels of ERc and 41% significant levels of PRc. No correlation was found between ERc and PRc and menopausal status of the patient, stage, cell type, or histologic grade of the tumor. A weak (P = 0.063) correlation between the presence of PRc and length of survival was also found, but there was no correlation between ERc and survival. Unlike the situation for breast cancer, measurement of ERc and PRc appears to add little of value to the clinical management of cervical carcinoma.

Adenocarcinoma↗
PubMed1987

Effect of serum proteins on estrogen-mediated receptor translocation in the superfused rat uterus.

In order to examine the effects of serum proteins on the biologic activity of estrogens, we superfused uteri from ovariectomized rats with Krebs-Ringer phosphate buffer (KRP), 4% human serum albumin (HSA) in KR or charcoal-stripped human plasma (HP), alone or with estradiol (E2), estrone (E1) or estriol (E3), 5 x 10(-10), 10(-9) and 10(-8) M. Following superfusion, the uteri were homogenized and the cytosol and nuclear receptors were measured by an exchange technique. Since we could detect no significant difference in the percent of receptors in the nucleus when the time of superfusion was varied from 30-120 min, all studies were done using a 30 min superfusion at a flow rate of 0.6 ml/min. In control studies using KRP alone (n = 12) 23.8 +/- 1.8 (mean +/- SEM) of the receptors were present in the nucleus at the end of the 30 min superfusion. Addition of E1, E2 or E3 5 x 10(-10) M resulted in a significant increase compared to controls in the percent of receptors in the nucleus. The percent of nuclear receptors was significantly greater for E2 and E3 (46.5 +/- 3.2% and 43.6 +/- 1.8%) compared to E1 (34.0 +/- 0.9%). Superfusions of uteri with either E2 or E3 at 10(-9) M or 10(-8) M resulted in a significantly greater percent of nuclear receptors compared to equimolar infusions of E1. When uteri were superfused with E1 at 5 x 10(-10), 10(-9) or 10(-8) M or with E3 at 5 x 10(-10) or 10(-9) M in HSA or HP the percent of nuclear receptors was not different compared to the respective infusion of equimolar concentrations of E1 or E3 in KR. However, superfusions of E2 5 x 10(-10), 10(-9) or 10(-8) M in HSA or HP resulted in a significant decrease in the percent nuclear receptors compared to the percent after equimolar superfusions of E2 in KR. Superfusions of E2 in HSA or HP resulted in the same percent of receptors in the nucleus. The percent of receptors in the nucleus increased with increasing concentrations of E2, but at each concentration the percent of receptors was the same with HA as with HP. Using the percent of nuclear receptors as an index of biological activity, E1 has less activity than either E2 or E3. Interaction with serum proteins does not modulate the activities of either E1 or E3, except at the concentration of 10(-8) M for E3.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

The effects of l-thyroxine and dexamethasone on steroid dynamics in male cynomologous monkeys.

Male cynomologous monkeys (M. fascicularis) were infused with [3H]androgens, [14C]estrogens and [3H]cortisol before and after the administration of l-thyroxine, (l-T4) 150 micrograms/day for 6 wk, dexamethasone 8 mg every 8 h for 3 doses and dexamethasone 1.0 mg/day for 8 days. Blood samples were obtained before each of the infusions and analyzed for endogenous T, A, E1, E2 and F concentrations, % free T and % free E2, sex hormone-binding globulin (SHBG) and cortisol binding globulin (CBG) capacity. When l-T4 was being administered, T4 and triiodothyronine (T3) concentrations were also measured. Blood samples were obtained during the infusions and analyzed for radioactivity as testosterone (T), androstenedione (A), dihydrotestosterone (DHT), estradiol (E1), estrone (E2), and cortisol (F). All urine was collected for 96 h and an aliquot of the pooled urine was analyzed for radioactivity as estrone and estradiol glucuronide. The administration of l-T4 for 6 wk to 3 monkeys resulted in a marked rise in T4 and T3 levels, from 4.8 +/- 0.4 micrograms/dl and from 136 +/- 6 to 515 +/- 71 ng/dl, respectively. MCRT, MCRE2 and MCRE1 did not change, but MCRA values increased slightly and MCRF increased 2-3 fold. [rho]T.E2 did not change but [rho]A.E1BM showed a slight but significant increase. The inter-conversions between the androgens and between the estrogens were not altered. There was a 2-3-fold increase in SHBG and a decrease in %FT but no change in %FE2 or CBG. The concentrations of T, A and DHT rose but there was no trend in the levels of the estrogens. The administration of dexamethasone 8 mg every 8 h for 3 doses or 1 mg/day for 8 days caused no changes in the MCRs for T, A, E1 and E2 but did cause a significant decrease in MCRF. Measurement of splanchnic and peripheral tissue extractions before and after acute dexamethasone administration in 1 monkey showed that the decrease in MCRF was the result of a marked decrease, 11-2%, in splanchnic extraction of F. The extractions of T and E2 were relatively unaffected. The concentrations of T and F fell but E2 remained the same. % FT and % FE2 rose slightly and the concentrations of SHBG and CBG were unchanged. The androgen interconversions and estrogen interconversions were not affected but [rho]T,E2BM and [rho]A,E1BM showed slight decreases.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1987

Androgenic and estrogenic metabolites in serum of mice fed dehydroepiandrosterone: relationship to antihyperglycemic effects.

The steroid prehormone, dehydroepiandrosterone (DHEA) has potent antihyperglycemic effects when fed in the diet of genetically diabetic C57BL/KsJ-db/db mice. The purpose of this investigation was to analyze changes in sex steroid levels in serum of mice fed DHEA, and to compare the antihyperglycemic potencies of the various metabolites in order to clarify the mechanism of DHEA action. Steroid radioimmunoassays showed that dietary DHEA entered the blood in high concentrations and was actively metabolized to both androgens (testosterone, T; dihydrotestosterone, DHT) and estrogens (estrone, E1; 17 beta-estradiol, E2). This metabolism did not require intact adrenal glands or gonads. In C57BL/KsJ normal (+/+) males, conversion of DHEA to androgens was the prominent feature; in db/db males, DHEA feeding not only increased serum T and DHT, but also serum E1 and E2 levels. The db/db mice had increased amounts of adipose tissue that sequestered more intravenously injected 3H-E2; this additional body fat could account for increased aromatization of DHEA-derived estrogen precursors. Comparisons of the relative antihyperglycemic potencies of androgenic and estrogenic steroid metabolites of DHEA in db/db mice showed that the estrogens and metabolites with estrogenic properties (androstenediol) or those convertible to estrogens (DHEA sulfate) were the most potent. Although 17 beta-E2 was effective by injection or per os, DHEA was effective only when administered per os, implicating alimentary tract conversion of DHEA to more biologically active reactants. Based on the pivotal position of DHEA as a prehormone for androgens, estrogens, and etiocholanolones, an explanation of the seemingly paradoxical effects exerted by this compound in blocking autoimmune disease, hyperglycemia, obesity, and neoplasia was proposed.

Androgens↗
PubMed1987

The effects of low-protein diet and testosterone on sex hormone-binding globulin capacity in male rabbits.

The effects of a low-protein high-carbohydrate (LPHC) diet (8% protein 65% to 72% carbohydrate) were compared to those of regular rabbit chow (14% to 16% protein 57% to 64% carbohydrate) on sex hormone-binding globulin (SHBG) capacity in 12 male rabbits. The six rabbits who were fed the LPHC diet for 8 weeks showed a significant increase in their mean SHBG capacity (mean +/- SE: from 70 +/- 16 nmol/L to 332 +/- 45 nmol/L, P less than .01) whereas the six rabbits fed the standard diet showed a slight decrease (from 106 +/- 22 nmol/L to 76 +/- 20 nmol/L, NS). These changes in SHBG capacity were mirrored by a decrease in percent-free T (from 2.64 +/- 0.26% to 1.64 +/- 0.16%, P less than .01) in the LPHC diet group and no change in percent-free T in the regular diet group (from 2.36 +/- 0.21% to 2.19 +/- 0.10%). The changes in SHBG capacity and percent-free T were not associated with significant changes in testosterone (T), free T, estradiol (E2), thyroxine, triiodothyronine, thyroxine-binding globulin, or cortisol binding globulin levels. In a subsequent experiment, testosterone cyclopentyl propionate (TCP) was administered to six male rabbits while on regular rabbit chow and again after 6 weeks of the LPHC diet. TCP administration did not cause any significant change in the SHBG capacity, but the LPHC resulted again in a significant (P less than .05) increase in SHBG capacity from 80 +/- 18 nmol/L. to 198 +/- 22 nmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗