Biomedical subjects

W Rosner

Publications and source records attributed to W Rosner.

At least 55 records · Page 3Linked to original sources

PubMed1988

Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men.

To study the ability of weight loss to reverse the hyperestrogenemia-induced hypogonadotropic hypogonadism that occurs in obese men, we measured the 24-h mean plasma free and total estradiol (E2), total estrone, FSH, LH, and free and total testosterone concentrations in 11 healthy obese men (100-305% above desirable body weight) and again 5-39 months later after weight loss of 26-129 kg and restabilization at the new weight. Weight loss produced significant increases in mean plasma total testosterone [240 +/- 116 (+/- SD, 8.5 +/- 4.0) to 377 +/- 113 ng/dL (13.0 +/- 4.0 nmol/L); P less than 0.01], free testosterone [9.5 +/- 5.0 (329 +/- 173) to 13.4 +/- 4.3 ng/dL (464 +/- 149 pmol/L); P less than 0.025], and FSH (6.5 +/- 4.7 to 10.9 +/- 8.5 IU/L; P less than 0.025). Plasma LH was lower than levels in normal men before and after weight loss and did not change significantly (10.3 +/- 4.8 and 10.8 +/- 6.8 IU/L, respectively). There was no change in plasma total E2 [54 +/- 26 (196 +/- 94) to 50 +/- 13 pg/mL (180 +/- 50 pmol/L)], free E2 [1.48 +/- 0.7 (5.37 +/- 2.54) to 1.33 +/- 0.42 pg/mL (4.83 +/- 1.45 pmol/L)], or total estrone [75 +/- 38 (280 +/- 140) to 82 +/- 24 (300 +/- 90) pmol/L], and sex hormone-binding globulin rose from 9.2 +/- 3.2 to 12.9 +/- 5.4 nmol/L (P less than 0.005). The increases in plasma free and total testosterone and sex hormone-binding globulin were proportional to the degree of weight loss. Thus, the hypogonadotropic hypogonadism was largely reversed by the weight loss without any decrease in hyperestrogenemia, its presumed cause. We postulate a change in hypothalamic-pituitary function with weight loss, such that GnRH-gonadotropin secretion becomes less sensitive to suppression by a given amount of estrogen.

Adult↗

PubMed1988

Partial reversal of the hypogonadotropic hypogonadism of obese men by administration of corticosuppressive doses of dexamethasone.

Obese men have hyperestrogenemia-induced hypogonadotropic hypogonadism (HHG), due, we believe, to increased rarmatization of adrenal androgens by the increased bulk of aromatase-containing adipose tissue. We studied the effects of corticosuppressive doses of dexamethasone (D) on 24-h mean plasma total and free estradiol (E2), estrone (E1), LH, FSH, total and free testosterone, delta 4-androstenedione (delta 4), and sex-hormone-binding globulin (SHBG) in nine obese men and five normal-weight controls. In the obese men, the following hormones fell: E2 [59 +/- 19 to 39 +/- 11 pg/ml (P less than 0.01)], E1 [93 +/- 41 to 50 +/- 25 pg/ml; (P less than 0.01)], delta 4-androstenedione [120 +/- 80 to 55 +/- 27 ng/dl; (P less than 0.02)]; free E2 [1.6 +/- 0.4 to 1.1 +/- 0.2 pg/ml; (P less than 0.01)], SHBG [12.8 +/- 5.3 to 8.2 +/- 3 nM/l; (P less than 0.04)]. FSH rose from 4.8 +/- 3.2 to 7.6 +/- 4.2 miu/ml (P less than 0.01). LH, total and free testosterone showed no significant change. In the nonobese men, there were decreases in total E2 [(34 +/- 6.8 to 25 +/- 10 pg/ml; P less than 0.04)], SHBG [16.8 +/- 7.5 to 10.4 +/- 2.0 nM/l: P less than .05.], free E2 [0.9 +/- 0.2 to 0.7 +/- 0.3 pg/ml: P less than 0.05], delta 4 [91.4 +/- 3.6 to 33.4 +/- 16.7 ng/dl; P less than .01] and total T [492 +/- 44 to 393 +/- 121 ng/dl; P less than 0.04]. There was no significant change in E1, FSH, LH or free T.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man.

The aim of this study was to determine if a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations. There is little information about the effects of specific dietary components on steroid hormone metabolism in humans. Testosterone concentrations in seven normal men were consistently higher after ten days on a high carbohydrate diet (468 +/- 34 ng/dl, mean +/- S.E.) than during a high protein diet (371 +/- 23 ng/dl, p less than 0.05) and were accompanied by parallel changes in sex hormone binding globulin (32.5 +/- 2.8 nmol/l vs. 23.4 +/- 1.6 nmol/l respectively, p less than 0.01). By contrast, cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet (7.74 +/- 0.71 micrograms/dl vs. 10.6 +/- 0.4 micrograms/dl respectively, p less than 0.05), and there were parallel changes in corticosteroid binding globulin concentrations (635 +/- 60 nmol/l vs. 754 +/- 31 nmol/l respectively, p less than 0.05). The diets were equal in total calories and fat. These consistent and reciprocal changes suggest that the ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins.

Adult↗

PubMed1987

Abnormal testicular function in men with primary hypothyroidism.

Myxedema in men is thought to cause infertility and impotence. Testicular function was investigated in eight consecutive men with primary hypothyroidism (autoimmune thyroiditis in five patients and amiodarone therapy in three patients). All had impotence that preceded the onset of hypothyroidism and did not improve with thyroid therapy. Gonadal function tests showed a hypergonadotropic state in five patients and hypogonadotropic hypogonadism in three patients including one with no response to luteinizing hormone-releasing hormone. Luteinizing hormone bioactivity was decreased in six patients and increased in two subjects who also had increased luteinizing hormone immunoreactivity. Serum testosterone and testosterone/estradiol-binding globulin concentrations were low in four of the patients. It is concluded that abnormalities of gonadal function are common in men with primary hypothyroidism.

Adult↗

PubMed1987

Binding of estradiol-17-fatty acid esters to plasma proteins.

The C-17 fatty acid esters of estradiol are a unique family of long-acting estrogens that circulate in blood. The unusual duration of the estrogenic action of these esters has been shown previously to correlate with their very slow rate of metabolism. However, in striking contrast to their slow rate of metabolism, the clearance of these esters from blood is relatively rapid, not very different from that of estradiol (E2). Studies on the effect of the size of the carboxylic acid moiety on the rates of both metabolism and clearance have suggested that an active process might be involved in the cellular uptake of these circulating esters, and this, in turn, raised the question of how E2-fatty acid esters are transported in blood. The binding of representative E2-17-fatty acid esters to both human and rat plasma proteins known to bind either E2 or fatty acids was investigated. As expected, both E2 and 5 alpha-dihydrotestosterone bound to human sex hormone-binding globulin, whereas none of the E2 esters bound to this human plasma protein. Similarly, E2 bound to rat alpha-fetoprotein (AFP) and unsaturated fatty acids bound to both human and rat AFP, but none of the E2 esters bound to AFP of either species. These steroid esters bind to lipoproteins. Over 85% of a representative ester, E2-17-stearate, partitioned in the lipoprotein fractions of both human and rat serum, while the synthetic short chain ester, E2-17 beta-acetate, like E2 itself, partitioned predominantly in the nonlipoprotein fraction of blood. These results demonstrate the unusual binding of a family of steroid hormones to plasma lipoproteins and open the possibility that they are transported into target cells through the mediation of lipoprotein receptors.

Animals↗

PubMed1987

Serum sex hormone-binding globulin in amiodarone-treated patients. A marker for tissue thyrotoxicosis.

The lodinated antiarrhythmic drug amiodarone frequently causes an elevation of the serum thyroxine (T4) level in patients who remain clinically euthyroid. Less frequently, true iodine-induced hyperthyroidism may occur. The clinical and laboratory distinction between these two conditions is often difficult. Since the serum sex hormone-binding globulin (SHBG) concentration is elevated in hyperthyroidism, this study was carried out to evaluate the serum SHBG concentration as a possible marker of hyperthyroidism in patients receiving amiodarone. Patients treated with amiodarone were divided into three groups: clinically euthyroid with normal serum T4 and triiodothyronine (T3) concentrations, clinically euthyroid with elevated serum T4 and normal T3 concentrations, and clinically hyperthyroid with elevated serum T4 and T3 concentrations. The mean serum SHBG concentration was significantly elevated in amiodarone-induced hyperthyroid patients, while it was normal in euthyroid patients treated with amiodarone who had normal or elevated serum T4 concentrations. The results suggest that the hyperthyroxinemia induced by amiodarone is not associated with excess thyroid hormone action in the liver unless the serum T3 concentration is also elevated.

Aged↗

PubMed1986

Specific binding of human corticosteroid-binding globulin to cell membranes.

Specific binding sites for corticosteroid-binding globulin were detected on membranes prepared from human prostates. The binding sites are typical of membrane receptors: they are saturable and specific and have high affinity. There was little specific binding at 4 degrees C and 23 degrees C. Maximal specific binding was obtained at 37 degrees C. Scatchard analysis revealed the presence of a single set of binding sites with an apparent dissociation constant of 8.7 X 10(-7) M and a binding capacity of 22 pmol/mg of membrane protein. The sites were specific for corticosteroid-binding globulin; binding was not inhibited by human testosterone/estradiol-binding globulin, by albumin, or by transferrin. The density of specific binding sites in membranes obtained from several organs from the rhesus monkey is consistent with the hypothesis that corticosteroid-binding globulin is involved in the transport of steroid hormones into target tissues.

Albumins↗

PubMed1986

Suppression of testosterone-estradiol binding globulin by medroxyprogesterone acetate in polycystic ovary syndrome.

Serum androgen binding capacity is decreased in hirsute women and normal women receiving medroxyprogesterone acetate. A sensitive radioimmunoassay was used to measure the main androgen binding protein, testosterone-estradiol-binding globulin, in 13 patients with hirsutism and the polycystic ovary syndrome. Testosterone-estradiol-binding globulin concentrations were determined before, during, and after treatment with medroxyprogesterone acetate. Testosterone-estradiol-binding globulin was lower in untreated polycystic ovary syndrome patients than in normal controls (21.9 +/- 3.7 versus 64 +/- 4 nmol/L, P less than .01). Administration of medroxyprogesterone acetate (400 mg intramuscularly every 15 days for nine months) to polycystic ovary syndrome patients caused a decrease of serum testosterone and further lowering of testosterone-estradiol-binding globulin (7.6 +/- 1.9 nmol/L, P less than .01). In two patients the concentration of testosterone-estradiol-binding globulin reached values as low as 0.9 and 0.8 nmol/L, approximately 1/60 and 1/70 of the normal level. Testosterone-estradiol-binding globulin returned to basal levels (15.1 +/- 1.3 nmol/L) between one and two years after discontinuation of medroxyprogesterone acetate. Corticosteroid binding globulin levels were normal in polycystic ovary syndrome and did not change with medroxyprogesterone acetate. It was concluded that: medroxyprogesterone acetate causes marked lowering of plasma testosterone-estradiol-binding globulin; the effect is not mediated by sex hormone levels; and the decrease in testosterone-estradiol-binding globulin offsets, at least partially, the beneficial action of medroxyprogesterone acetate.

Female↗

PubMed1986

Steroid-binding proteins in primate plasma.

We used immunological techniques to compare the serum corticosteroid-binding globulins (CBG) and testosterone-estradiol-binding globulins (TeBG) of Old World primates (man, chimpanzee, cynomologus, and rhesus), New World monkeys (squirrel and owl), and prosimians (galago and lemur). Four different antihuman TeBG antisera could not differentiate human and chimpanzee TeBG and recognized the galago and lemur TeBG as similar as well as the rhesus and cynomologus TeBG, as similar. Western blots of serum subjected to sodium dodecyl sulfate gel electrophoresis, with detection by an anti-TeBG antiserum, showed similar patterns of distribution of the two molecular species of TeBG for all of the New World primates and the owl monkey. The abundance of the two TeBG species was reversed in squirrel monkey serum, while lemur and galago displayed only a single band. Four different antihuman CBG antisera grouped together the CBGs of human and chimpanzee, rhesus and cynomologus, and lemur and galago. The squirrel monkey has a CBG with a markedly decreased affinity for cortisol; all four antisera perceived its CBG as much more immunologically distant from the human protein than that of the owl monkey. Indeed, three of the four antisera grouped squirrel monkey CBG with that of the prosimians, while one antiserum saw squirrel monkey CBG as even more distant from the human protein than the CBG of the primitive primates, the prosimians.

Animals↗

PubMed1985

Testosterone-estradiol-binding globulin binds to human prostatic cell membranes.

Specific binding sites for human testosterone-estradiol-binding globulin have been found on human prostatic cell membranes. Scatchard analysis reveals both a high and a low affinity binding site for [125I]testosterone-estradiol-binding globulin. The high affinity site is specific for testosterone-estradiol-binding globulin, whereas the low affinity site also binds human corticosteroid-binding globulin and human transferrin.

Binding Sites↗

PubMed1985

Persistent pituitary resistance to thyroid hormone in congenital versus later-onset hypothyroidism.

The pituitary and peripheral responses to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2 and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. In normal individuals the peak TSH, alpha, and TSH-beta response to TRH was significantly decreased with 0.1 mg L-T4 or 0.05 mg L-T3 daily and was suppressed with 0.2 and 0.4 mg L-T4 or 0.2 mg L-T3 daily; serum cholesterol and triglyceride decreased significantly with 0.2 or 0.4 mg L-T4 or 0.2 mg L-T3 daily; testosterone-estradiol binding globulin (TeBG) increased significantly at the same doses. In congenitally hypothyroid patients receiving 0.2 mg L-T4 daily, the mean peak TSH after TRH was 24 +/- 17 microU/ml, whereas in patients with an ectopic thyroid or adult-onset hypothyroidism the peak TSH was significantly less at 5.9 +/- 8.8 and 5.5 +/- 5.7 microU/ml, respectively. Only at the highest doses of L-T4 (0.4 mg/day) or L-T3 (0.2 mg/day) was the TSH response to TRH suppressed in the congenitally hypothyroid group. The alpha and TSH-beta subunit levels followed those of TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1985

Size isomers of testosterone-estradiol-binding globulin exist in the plasma of individual men and women.

We isolated testosterone-estradiol-binding globulin TeBG rapidly and in high yield from pooled pregnancy plasma. It showed two bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). Both bands stained with three different monoclonal antibodies to TeBG, thus demonstrating their immunological similarity. Freshly drawn, individual sera, from men, women, and pregnant patients were submitted to microaffinity chromatography, a procedure which partially purifies TeBG in approximately 4 hr. The partially purified plasma was submitted to SDS PAGE, followed by immunoblotting. The blotted TeBG exhibited the same two bands seen in the isolated, purified protein. The size heterogeneity observed in TeBG purified to: proteolysis occurring during isolation; a peculiarity of pregnancy plasma; or heterogeneity attendant upon the use of pooled plasma for isolation.

Chromatography, Affinity↗

PubMed1985

Synthesis and evaluation of potential radioligands for the progesterone receptor.

Several steroidal analogues were synthesized as potential gamma-emitting radioligands for the progesterone receptor. Each of these compounds was tested as an inhibitor of the specific binding of [3H]-17 alpha,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (R5020) to the progesterone receptor in rabbit uterine cytosol. R5020 is a well-known progestin with high affinity for the receptor. Of the compounds synthesized, aromatic N-substituted C-17 steroidal carboxamides inhibited the binding only poorly. Three compounds, 16 alpha-iodo-4-estren-17 beta-ol-3-one, 17 alpha-[2(E)-iodovinyl]-4-estren-17 beta-ol-3-one, and 17 alpha-[2(Z)-iodovinyl]-4-estren-17 beta-ol-3-one were excellent competitors, each having a Ki less than or equal to that of the natural progestin, progesterone. Since similar iodinated analogues of estrogens have been shown to be extremely stable both in vivo and in vitro, these compounds are potentially useful ligands for the progesterone receptor.

Animals↗

PubMed1985

E-17 alpha-(2-[125I]iodovinyl)-19-nortestosterone: the synthesis of a gamma-emitting ligand for the progesterone receptor.

We have synthesized a gamma-emitting steroid, E-17 alpha-(2-[125I]iodovinyl)-19-nortestosterone (E-IVNT), which is a useful ligand for the sensitive and accurate assay of the progesterone receptor. The synthetic scheme is rapid and is performed with readily available materials. This compound, [125I]E-IVNT, is stable and binds with high affinity to the progesterone receptor.

Affinity Labels↗

PubMed1985

Plasma steroid-binding proteins in the cysts of gross cystic disease of the breast.

Breast cyst fluids from 33 patients who underwent cyst aspiration were examined for their content of total protein, albumin, corticosteroid-binding globulin (CBG), and testosterone-estradiol-binding globulin (TeBG). Two distinct populations of cysts, based on their chloride concentration, were found. Both types of cysts had markedly reduced concentrations of the three plasma proteins compared to plasma levels. Concentrations of the proteins in the low chloride (less than 40 meq/liter) cysts were substantially lower than those in the high chloride (greater than 40 meq/liter) ones. Relative to albumin, both CBG and TeBG were excluded from low chloride cysts, whereas relative to one another, the ratios of these two steroid-binding proteins were the same as those in plasma. We conclude that there are specific mechanisms in breast cysts regulating the ingress and/or egress of CBG and TeBG.

Albumins↗

PubMed1984

Human corticosteroid binding globulin is secreted by a hepatoma-derived cell line.

We used a sensitive radioimmunoassay for corticosteroid-binding-globulin (CBG) to demonstrate that a human hepatoma-derived cell line secretes a protein which: (a) the radioimmunoassay cannot distinguish from CBG; (b) has the same Stokes' radius as CBG; (c) is absorbed by a steroid affinity column which is specific for CBG.

Carcinoma, Hepatocellular↗

PubMed1984

Use of bromocriptine in a patient with generalized resistance to thyroid hormone.

A 50-yr-old man with a large goiter had elevated serum levels of T4 (22 micrograms/dl), T3 (228 ng/dl), and free T4 (6.6 ng/dl), a high 24-h 131I-thyroidal uptake (69%), and an elevated TSH level (3.6 microU/ml), as well as hyperresponsiveness of TSH to TRH (peak TSH, 47 microU/ml). Normal serum alpha-subunit concentrations and sella turcica films mitigated against the presence of a pituitary tumor. A normal basal metabolic rate and minimally elevated concentration of testosterone-estradiol binding globulin were consistent with generalized resistance to thyroid hormone. Mild lactotroph resistance was also present. The patient was given bromocriptine for 16 months (2.5-10 mg daily). Basal serum TSH levels decreased (less than 0.3-2 microU/ml), as did the TSH response to TRH; serum T4 levels (14-17 micrograms/dl); and 24-h 131I-thyroidal uptake (28%) were reduced. Serum T3 levels, however, changed little. The thyroid gland decreased to normal size, and the basal metabolic rate and testosterone-estradiol binding globulin remained normal. Bromocriptine was stopped for 4 months. Serum TSH increased to 4.5 microU/ml; T4 and T3 increased to 27 micrograms/dl and 328 ng/dl; the patient became clinically mildly hyperthyroid. Thus, bromocriptine in this patient was useful in decreasing TSH secretion and decreasing goiter size, while maintaining clinical euthyroidism. Only a small amount of TSH was necessary to maintain iodine uptake and thyroid hormone synthesis and secretion in a responsive thyroid gland. We speculate that this patient may be secreting a highly bioactive form of TSH and/or have increased thyroid sensitivity to TSH.

Bromocriptine↗

PubMed1984

Hormonal influences on the secretion of steroid-binding proteins by a human hepatoma-derived cell line.

We examined the influence of numerous substances on the secretion of corticosteroid-binding globulin (CBG) and testosterone-estradiol binding globulin (TeBG) by a human hepatoma-derived cell line. Thyroxine, at physiologic concentrations, resulted in an increased secretion of TeBG but not CBG. Estrogens, antiestrogens, and androgens were without effect on either of these binding proteins.

Animals↗